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11.6: Drugs for Non-prokaryote Microbes - Biology

11.6: Drugs for Non-prokaryote Microbes - Biology


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Learning Objectives

  • Explain the differences between modes of action of drugs that target fungi, protozoa, helminths, and viruses

Because fungi, protozoa, and helminths are eukaryotic, their cells are very similar to human cells, making it more difficult to develop drugs with selective toxicity. Additionally, viruses replicate within human host cells, making it difficult to develop drugs that are selectively toxic to viruses or virus-infected cells. Despite these challenges, there are antimicrobial drugs that target fungi, protozoa, helminths, and viruses, and some even target more than one type of microbe. Table (PageIndex{1}), Table (PageIndex{2}), Table (PageIndex{3}), and Table (PageIndex{4}) provide examples for antimicrobial drugs in these various classes.

Antifungal Drugs

The most common mode of action for antifungal drugs is the disruption of the cell membrane. Antifungals take advantage of small differences between fungi and humans in the biochemical pathways that synthesize sterols. The sterols are important in maintaining proper membrane fluidity and, hence, proper function of the cell membrane. For most fungi, the predominant membrane sterol is ergosterol. Because human cell membranes use cholesterol, instead of ergosterol, antifungal drugs that target ergosterol synthesis are selectively toxic (Figure (PageIndex{1})).

The imidazoles are synthetic fungicides that disrupt ergosterol biosynthesis; they are commonly used in medical applications and also in agriculture to keep seeds and harvested crops from molding. Examples include miconazole, ketoconazole, and clotrimazole, which are used to treat fungal skin infections such as ringworm, specifically tinea pedis (athlete’s foot), tinea cruris (jock itch), and tinea corporis. These infections are commonly caused by dermatophytes of the genera Trichophyton, Epidermophyton, and Microsporum. Miconazole is also used predominantly for the treatment of vaginal yeast infections caused by the fungus Candida, and ketoconazole is used for the treatment of tinea versicolor and dandruff, which both can be caused by the fungus Malassezia.

The triazole drugs, including fluconazole, also inhibit ergosterol biosynthesis. However, they can be administered orally or intravenously for the treatment of several types of systemic yeast infections, including oral thrush and cryptococcal meningitis, both of which are prevalent in patients with AIDS. The triazoles also exhibit more selective toxicity, compared with the imidazoles, and are associated with fewer side effects.

The allylamines, a structurally different class of synthetic antifungal drugs, inhibit an earlier step in ergosterol biosynthesis. The most commonly used allylamine is terbinafine (marketed under the brand name Lamisil), which is used topically for the treatment of dermatophytic skin infections like athlete’s foot, ringworm, and jock itch. Oral treatment with terbinafine is also used for the treatment of fingernail and toenail fungus, but it can be associated with the rare side effect of hepatotoxicity.

The polyenes are a class of antifungal agents naturally produced by certain actinomycete soil bacteria and are structurally related to macrolides. These large, lipophilic molecules bind to ergosterol in fungal cytoplasmic membranes, thus creating pores. Common examples include nystatin and amphotericin B. Nystatin is typically used as a topical treatment for yeast infections of the skin, mouth, and vagina, but may also be used for intestinal fungal infections. The drug amphotericin B is used for systemic fungal infections like aspergillosis, cryptococcal meningitis, histoplasmosis, blastomycosis, and candidiasis. Amphotericin B was the only antifungal drug available for several decades, but its use is associated with some serious side effects, including nephrotoxicity (kidney toxicity).

Amphotericin B is often used in combination with flucytosine, a fluorinated pyrimidine analog that is converted by a fungal-specific enzyme into a toxic product that interferes with both DNA replication and protein synthesis in fungi. Flucytosine is also associated with hepatotoxicity (liver toxicity) and bone marrow depression.

Beyond targeting ergosterol in fungal cell membranes, there are a few antifungal drugs that target other fungal structures (Figure (PageIndex{2})). The echinocandins, including caspofungin, are a group of naturally produced antifungal compounds that block the synthesis of β(1→3) glucan found in fungal cell walls but not found in human cells. This drug class has the nickname “penicillin for fungi.” Caspofungin is used for the treatment of aspergillosis as well as systemic yeast infections.

Although chitin is only a minor constituent of fungal cell walls, it is also absent in human cells, making it a selective target. The polyoxins and nikkomycins are naturally produced antifungals that target chitin synthesis. Polyoxins are used to control fungi for agricultural purposes, and nikkomycin Z is currently under development for use in humans to treat yeast infections and Valley fever (coccidioidomycosis), a fungal disease prevalent in the southwestern US.1

The naturally produced antifungal griseofulvin is thought to specifically disrupt fungal cell division by interfering with microtubules involved in spindle formation during mitosis. It was one of the first antifungals, but its use is associated with hepatotoxicity. It is typically administered orally to treat various types of dermatophytic skin infections when other topical antifungal treatments are ineffective.

There are a few drugs that act as antimetabolites against fungal processes. For example, atovaquone, a representative of the naphthoquinone drug class, is a semisynthetic antimetabolite for fungal and protozoal versions of a mitochondrial cytochrome important in electron transport. Structurally, it is an analog of coenzyme Q, with which it competes for electron binding. It is particularly useful for the treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii. The antibacterial sulfamethoxazole-trimethoprim combination also acts as an antimetabolite against P. jirovecii.

Table (PageIndex{1}) shows the various therapeutic classes of antifungal drugs, categorized by mode of action, with examples of each.

Table (PageIndex{1}): Common Antifungal Drugs
Mechanism of ActionDrug ClassSpecific DrugsClinical Uses
Inhibit ergosterol synthesisImidazolesMiconazole, ketoconazole, clotrimazoleFungal skin infections and vaginal yeast infections
TriazolesFluconazoleSystemic yeast infections, oral thrush, and cryptococcal meningitis
AllylaminesTerbinafineDermatophytic skin infections (athlete’s foot, ring worm, jock itch), and infections of fingernails and toenails
Bind ergosterol in the cell membrane and create pores that disrupt the membranePolyenesNystatinUsed topically for yeast infections of skin, mouth, and vagina; also used for fungal infections of the intestine
Amphotericin BVariety systemic fungal infections
Inhibit cell wall synthesisEchinocandinsCaspofunginAspergillosis and systemic yeast infections
Not applicableNikkomycin ZCoccidioidomycosis (Valley fever) and yeast infections
Inhibit microtubules and cell divisionNot applicableGriseofulvinDermatophytic skin infections

Exercise (PageIndex{1})

How is disruption of ergosterol biosynthesis an effective mode of action for antifungals?

Treating a Fungal Infection of the Lungs

Jack, a 48-year-old engineer, is HIV positive but generally healthy thanks to antiretroviral therapy (ART). However, after a particularly intense week at work, he developed a fever and a dry cough. He assumed that he just had a cold or mild flu due to overexertion and didn’t think much of it. However, after about a week, he began to experience fatigue, weight loss, and shortness of breath. He decided to visit his physician, who found that Jack had a low level of blood oxygenation. The physician ordered blood testing, a chest X-ray, and the collection of an induced sputum sample for analysis. His X-ray showed a fine cloudiness and several pneumatoceles (thin-walled pockets of air), which indicated Pneumocystis pneumonia (PCP), a type of pneumonia caused by the fungus Pneumocystis jirovecii. Jack’s physician admitted him to the hospital and prescribed Bactrim, a combination of sulfamethoxazole and trimethoprim, to be administered intravenously.

P. jirovecii is a yeast-like fungus with a life cycle similar to that of protozoans. As such, it was classified as a protozoan until the 1980s. It lives only in the lung tissue of infected persons and is transmitted from person to person, with many people exposed as children. Typically, P. jirovecii only causes pneumonia in immunocompromised individuals. Healthy people may carry the fungus in their lungs with no symptoms of disease. PCP is particularly problematic among HIV patients with compromised immune systems.

PCP is usually treated with oral or intravenous Bactrim, but atovaquone or pentamidine (another antiparasitic drug) are alternatives. If not treated, PCP can progress, leading to a collapsed lung and nearly 100% mortality. Even with antimicrobial drug therapy, PCP still is responsible for 10% of HIV-related deaths.

The cytological examination, using direct immunofluorescence assay (DFA), of a smear from Jack’s sputum sample confirmed the presence of P. jirovecii (Figure (PageIndex{3})). Additionally, the results of Jack’s blood tests revealed that his white blood cell count had dipped, making him more susceptible to the fungus. His physician reviewed his ART regimen and made adjustments. After a few days of hospitalization, Jack was released to continue his antimicrobial therapy at home. With the adjustments to his ART therapy, Jack’s CD4 counts began to increase and he was able to go back to work.

Antiprotozoan Drugs

There are a few mechanisms by which antiprotozoan drugs target infectious protozoans (Table (PageIndex{3})). Some are antimetabolites, such as atovaquone, proguanil, and artemisinins. Atovaquone, in addition to being antifungal, blocks electron transport in protozoans and is used for the treatment of protozoan infections including malaria, babesiosis, and toxoplasmosis. Proguanil is another synthetic antimetabolite that is processed in parasitic cells into its active form, which inhibits protozoan folic acid synthesis. It is often used in combination with atovaquone, and the combination is marketed as Malarone for both malaria treatment and prevention.

Artemisinin, a plant-derived antifungal first discovered by Chinese scientists in the 1970s, is quite effective against malaria. Semisynthetic derivatives of artemisinin are more water soluble than the natural version, which makes them more bioavailable. Although the exact mechanism of action is unclear, artemisinins appear to act as prodrugs that are metabolized by target cells to produce reactive oxygen species (ROS) that damage target cells. Due to the rise in resistance to antimalarial drugs, artemisinins are also commonly used in combination with other antimalarial compounds in artemisinin-based combination therapy (ACT).

Several antimetabolites are used for the treatment of toxoplasmosis caused by the parasite Toxoplasma gondii. The synthetic sulfa drug sulfadiazine competitively inhibits an enzyme in folic acid production in parasites and can be used to treat malaria and toxoplasmosis. Pyrimethamine is a synthetic drug that inhibits a different enzyme in the folic acid production pathway and is often used in combination with sulfadoxine (another sulfa drug) for the treatment of malariaor in combination with sulfadiazine for the treatment of toxoplasmosis. Side effects of pyrimethamine include decreased bone marrow activity that may cause increased bruising and low red blood cell counts. When toxicity is a concern, spiramycin, a macrolide protein synthesis inhibitor, is typically administered for the treatment of toxoplasmosis.

Two classes of antiprotozoan drugs interfere with nucleic acid synthesis: nitroimidazoles and quinolines. Nitroimidazoles, including semisynthetic metronidazole, which was discussed previously as an antibacterial drug, and synthetic tinidazole, are useful in combating a wide variety of protozoan pathogens, such as Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis. Upon introduction into these cells in low-oxygen environments, nitroimidazoles become activated and introduce DNA strand breakage, interfering with DNA replication in target cells. Unfortunately, metronidazole is associated with carcinogenesis (the development of cancer) in humans.

Another type of synthetic antiprotozoan drug that has long been thought to specifically interfere with DNA replication in certain pathogens is pentamidine. It has historically been used for the treatment of African sleeping sickness (caused by the protozoan Trypanosoma brucei) and leishmaniasis (caused by protozoa of the genus Leishmania), but it is also an alternative treatment for the fungus Pneumocystis. Some studies indicate that it specifically binds to the DNA found within kinetoplasts (kDNA; long mitochondrion-like structures unique to trypanosomes), leading to the cleavage of kDNA. However, nuclear DNA of both the parasite and host remain unaffected. It also appears to bind to tRNA, inhibiting the addition of amino acids to tRNA, thus preventing protein synthesis. Possible side effects of pentamidine use include pancreatic dysfunction and liver damage.

The quinolines are a class of synthetic compounds related to quinine, which has a long history of use against malaria. Quinolines are thought to interfere with heme detoxification, which is necessary for the parasite’s effective breakdown of hemoglobin into amino acids inside red blood cells. The synthetic derivatives chloroquine, quinacrine (also called mepacrine), and mefloquine are commonly used as antimalarials, and chloroquine is also used to treat amebiasis typically caused by Entamoeba histolytica. Long-term prophylactic use of chloroquine or mefloquine may result in serious side effects, including hallucinations or cardiac issues. Patients with glucose-6-phosphate dehydrogenase deficiency experience severe anemia when treated with chloroquine.

Table (PageIndex{2}): Common Antiprotozoan Drugs
Mechanism of ActionDrug ClassSpecific DrugsClinical Uses
Inhibit electron transport in mitochondriaNaphthoquinoneAtovaquoneMalaria, babesiosis, and toxoplasmosis
Inhibit folic acid synthesisNot applicableProquanilCombination therapy with atovaquone for malaria treatment and prevention
SulfonamideSulfadiazineMalaria and toxoplasmosis
Not applicablePyrimethamineCombination therapy with sulfadoxine (sulfa drug) for malaria
Produces damaging reactive oxygen speciesNot applicableArtemisininCombination therapy to treat malaria
Inhibit DNA synthesisNitroimidazolesMetronidazole, tinidazoleInfections caused by Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis
Not applicablePentamidineAfrican sleeping sickness and leishmaniasis
Inhibit heme detoxificationQuinolinesChloroquineMalaria and infections with E. histolytica
Mepacrine, mefloquineMalaria

Exercise (PageIndex{2})

List two modes of action for antiprotozoan drugs.

Antihelminthic Drugs

Because helminths are multicellular animal eukaryotes like humans, developing drugs with selective toxicity against them is extremely challenging. Despite this, several effective classes have been developed (Table (PageIndex{3})). Synthetic benzimidazoles, like mebendazole and albendazole, bind to helminthic β-tubulin, preventing microtubule formation. Microtubules in the intestinal cells of the worms seem to be particularly affected, leading to a reduction in glucose uptake. Besides their activity against a broad range of helminths, benzimidazoles are also active against many protozoans, fungi, and viruses, and their use for inhibiting mitosis and cell cycle progression in cancer cells is under study.2 Possible side effects of their use include liver damage and bone marrow suppression.

The avermectins are members of the macrolide family that were first discovered from a Japanese soil isolate, Streptomyces avermectinius. A more potent semisynthetic derivative of avermectin is ivermectin, which binds to glutamate-gated chloride channels specific to invertebrates including helminths, blocking neuronal transmission and causing starvation, paralysis, and death of the worms. Ivermectin is used to treat roundworm diseases, including onchocerciasis (also called river blindness, caused by the worm Onchocerca volvulus) and strongyloidiasis (caused by the worm Strongyloides stercoralis or S. fuelleborni). Ivermectin also can also treat parasitic insects like mites, lice, and bed bugs, and is nontoxic to humans.

Niclosamide is a synthetic drug that has been used for over 50 years to treat tapeworm infections. Although its mode of action is not entirely clear, niclosamide appears to inhibit ATP formation under anaerobic conditions and inhibit oxidative phosphorylation in the mitochondria of its target pathogens. Niclosamide is not absorbed from the gastrointestinal tract, thus it can achieve high localized intestinal concentrations in patients. Recently, it has been shown to also have antibacterial, antiviral, and antitumor activities.345

Another synthetic antihelminthic drug is praziquantel, which used for the treatment of parasitic tapeworms and liver flukes, and is particularly useful for the treatment of schistosomiasis (caused by blood flukes from three genera of Schistosoma). Its mode of action remains unclear, but it appears to cause the influx of calcium into the worm, resulting in intense spasm and paralysis of the worm. It is often used as a preferred alternative to niclosamide in the treatment of tapeworms when gastrointestinal discomfort limits niclosamide use.

The thioxanthenones, another class of synthetic drugs structurally related to quinine, exhibit antischistosomal activity by inhibiting RNA synthesis. The thioxanthenone lucanthone and its metabolite hycanthone were the first used clinically, but serious neurological, gastrointestinal, cardiovascular, and hepatic side effects led to their discontinuation. Oxamniquine, a less toxic derivative of hycanthone, is only effective against S. mansoni, one of the three species known to cause schistosomiasis in humans. Praziquantel was developed to target the other two schistosome species, but concerns about increasing resistance have renewed interest in developing additional derivatives of oxamniquine to target all three clinically important schistosome species.

Table (PageIndex{3}): Common Antihelminthic Drugs
Mechanism of ActionDrug ClassSpecific DrugsClinical Uses
Inhibit microtubule formation, reducing glucose uptakeBenzimidazolesMebendazole, albendazoleVariety of helminth infections
Block neuronal transmission, causing paralysis and starvationAvermectinsIvermectinRoundworm diseases, including river blindness and strongyloidiasis, and treatment of parasitic insects
Inhibit ATP productionNot applicableNiclosamideIntestinal tapeworm infections
Induce calcium influxNot applicablePraziquantelSchistosomiasis (blood flukes)
Inhibit RNA synthesisThioxanthenonesLucanthone, hycanthone, oxamniquineSchistosomiasis (blood flukes)

Exercise (PageIndex{3})

Why are antihelminthic drugs difficult to develop?

Antiviral Drugs

Unlike the complex structure of fungi, protozoa, and helminths, viral structure is simple, consisting of nucleic acid, a protein coat, viral enzymes, and, sometimes, a lipid envelope. Furthermore, viruses are obligate intracellular pathogens that use the host’s cellular machinery to replicate. These characteristics make it difficult to develop drugs with selective toxicity against viruses.

Many antiviral drugs are nucleoside analogs and function by inhibiting nucleic acid biosynthesis. For example, acyclovir(marketed as Zovirax) is a synthetic analog of the nucleoside guanosine (Figure (PageIndex{4})). It is activated by the herpes simplex viral enzyme thymidine kinase and, when added to a growing DNA strand during replication, causes chain termination. Its specificity for virus-infected cells comes from both the need for a viral enzyme to activate it and the increased affinity of the activated form for viral DNA polymerase compared to host cell DNA polymerase. Acyclovir and its derivatives are frequently used for the treatment of herpes virus infections, including genital herpes, chickenpox, shingles, Epstein-Barr virus infections, and cytomegalovirus infections. Acyclovir can be administered either topically or systemically, depending on the infection. One possible side effect of its use includes nephrotoxicity. The drug adenine-arabinoside, marketed as vidarabine, is a synthetic analog to deoxyadenosine that has a mechanism of action similar to that of acyclovir. It is also effective for the treatment of various human herpes viruses. However, because of possible side effects involving low white blood cell counts and neurotoxicity, treatment with acyclovir is now preferred.

Ribavirin, another synthetic guanosine analog, works by a mechanism of action that is not entirely clear. It appears to interfere with both DNA and RNA synthesis, perhaps by reducing intracellular pools of guanosine triphosphate (GTP). Ribavarin also appears to inhibit the RNA polymerase of hepatitis C virus. It is primarily used for the treatment of the RNA viruses like hepatitis C (in combination therapy with interferon) and respiratory syncytial virus. Possible side effects of ribavirin use include anemia and developmental effects on unborn children in pregnant patients. In recent years, another nucleotide analog, sofosbuvir (Solvaldi), has also been developed for the treatment of hepatitis C. Sofosbuvir is a uridine analog that interferes with viral polymerase activity. It is commonly coadministered with ribavirin, with and without interferon.

Inhibition of nucleic acid synthesis is not the only target of synthetic antivirals. Although the mode of action of amantadine and its relative rimantadine are not entirely clear, these drugs appear to bind to a transmembrane protein that is involved in the escape of the influenza virus from endosomes. Blocking escape of the virus also prevents viral RNA release into host cells and subsequent viral replication. Increasing resistance has limited the use of amantadine and rimantadine in the treatment of influenza A. Use of amantadine can result in neurological side effects, but the side effects of rimantadine seem less severe. Interestingly, because of their effects on brain chemicals such as dopamine and NMDA (N-methyl D-aspartate), amantadine and rimantadine are also used for the treatment of Parkinson’s disease.

Neuraminidase inhibitors, including olsetamivir (Tamiflu), zanamivir (Relenza), and peramivir (Rapivab), specifically target influenza viruses by blocking the activity of influenza virus neuraminidase, preventing the release of the virus from infected cells. These three antivirals can decrease flu symptoms and shorten the duration of illness, but they differ in their modes of administration: olsetamivir is administered orally, zanamivir is inhaled, and peramivir is administered intravenously. Resistance to these neuraminidase inhibitors still seems to be minimal.

Pleconaril is a synthetic antiviral under development that showed promise for the treatment of picornaviruses. Use of pleconaril for the treatment of the common cold caused by rhinoviruses was not approved by the FDA in 2002 because of lack of proven effectiveness, lack of stability, and association with irregular menstruation. Its further development for this purpose was halted in 2007. However, pleconaril is still being investigated for use in the treatment of life-threatening complications of enteroviruses, such as meningitis and sepsis. It is also being investigated for use in the global eradication of a specific enterovirus, polio.6 Pleconaril seems to work by binding to the viral capsid and preventing the uncoating of viral particles inside host cells during viral infection.

Viruses with complex life cycles, such as HIV, can be more difficult to treat. First, HIV targets CD4-positive white blood cells, which are necessary for a normal immune response to infection. Second, HIV is a retrovirus, meaning that it converts its RNA genome into a DNA copy that integrates into the host cell’s genome, thus hiding within host cell DNA. Third, the HIV reverse transcriptase lacks proofreading activity and introduces mutations that allow for rapid development of antiviral drug resistance. To help prevent the emergence of resistance, a combination of specific synthetic antiviral drugs is typically used in ART for HIV (Figure).

The reverse transcriptase inhibitors block the early step of converting viral RNA genome into DNA, and can include competitive nucleoside analog inhibitors (e.g., azidothymidine/zidovudine, or AZT) and non-nucleoside noncompetitive inhibitors (e.g., etravirine) that bind reverse transcriptase and cause an inactivating conformational change. Drugs called protease inhibitors (e.g., ritonavir) block the processing of viral proteins and prevent viral maturation. Protease inhibitors are also being developed for the treatment of other viral types.7 For example, simeprevir (Olysio) has been approved for the treatment of hepatitis C and is administered with ribavirin and interferon in combination therapy. The integrase inhibitors (e.g., raltegravir), block the activity of the HIV integrase responsible for the recombination of a DNA copy of the viral genome into the host cell chromosome. Additional drug classes for HIV treatment include the CCR5 antagonists and the fusion inhibitors (e.g., enfuviritide), which prevent the binding of HIV to the host cell coreceptor (chemokine receptor type 5 [CCR5]) and the merging of the viral envelope with the host cell membrane, respectively. Table (PageIndex{4}) shows the various therapeutic classes of antiviral drugs, categorized by mode of action, with examples of each.

Table (PageIndex{4}): Common Antiviral Drugs
Mechanism of ActionDrugClinical Uses
Nucleoside analog inhibition of nucleic acid synthesisAcyclovirHerpes virus infections
Azidothymidine/zidovudine (AZT)HIV infections
RibavirinHepatitis C virus and respiratory syncytial virus infections
VidarabineHerpes virus infections
SofosbuvirHepatitis C virus infections
Non-nucleoside noncompetitive inhibitionEtravirineHIV infections
Inhibit escape of virus from endosomesAmantadine, rimantadineInfections with influenza virus
Inhibit neuraminadaseOlsetamivir, zanamivir, peramivirInfections with influenza virus
Inhibit viral uncoatingPleconarilSerious enterovirus infections
Inhibition of proteaseRitonavirHIV infections
SimeprevirHepatitis C virus infections
Inhibition of integraseRaltegravirHIV infections
Inhibition of membrane fusionEnfuviritideHIV infections

Exercise (PageIndex{4})

Why is HIV difficult to treat with antivirals?

To learn more about the various classes of antiretroviral drugs used in the ART of HIV infection, explore each of the drugs in the HIV drug classes provided by US Department of Health and Human Services at this website.

Key Concepts and Summary

  • Because fungi, protozoans, and helminths are eukaryotic organisms like human cells, it is more challenging to develop antimicrobial drugs that specifically target them. Similarly, it is hard to target viruses because human viruses replicate inside of human cells.
  • Antifungal drugs interfere with ergosterol synthesis, bind to ergosterol to disrupt fungal cell membrane integrity, or target cell wall-specific components or other cellular proteins.
  • Antiprotozoan drugs increase cellular levels of reactive oxygen species, interfere with protozoal DNA replication (nuclear versus kDNA, respectively), and disrupt heme detoxification.
  • Antihelminthic drugs disrupt helminthic and protozoan microtubule formation; block neuronal transmissions; inhibit anaerobic ATP formation and/or oxidative phosphorylation; induce a calcium influx in tapeworms, leading to spasms and paralysis; and interfere with RNA synthesis in schistosomes.
  • Antiviral drugs inhibit viral entry, inhibit viral uncoating, inhibit nucleic acid biosynthesis, prevent viral escape from endosomes in host cells, and prevent viral release from infected cells.
  • Because it can easily mutate to become drug resistant, HIV is typically treated with a combination of several antiretroviral drugs, which may include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and drugs that interfere with viral binding and fusion to initiate infection.

Footnotes

  1. Centers for Disease Control and Prevention. “Valley Fever: Awareness Is Key.” www.cdc.gov/features/valleyfever/. Accessed June 1, 2016.
  2. B. Chu et al. “A Benzimidazole Derivative Exhibiting Antitumor Activity Blocks EGFR and HER2 Activity and Upregulates DR5 in Breast Cancer Cells.” Cell Death and Disease 6 (2015):e1686
  3. J.-X. Pan et al. “Niclosamide, An Old Antihelminthic Agent, Demonstrates Antitumor Activity by Blocking Multiple Signaling Pathways of Cancer Stem Cells.” Chinese Journal of Cancer 31 no. 4 (2012):178–184.
  4. F. Imperi et al. “New Life for an Old Drug: The Anthelmintic Drug Niclosamide Inhibits Pseudomonas aeruginosa Quorum Sensing.” Antimicrobial Agents and Chemotherapy 57 no. 2 (2013):996-1005.
  5. A. Jurgeit et al. “Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects.” PLoS Pathogens 8 no. 10 (2012):e1002976.
  6. M.J. Abzug. “The Enteroviruses: Problems in Need of Treatments.” Journal of Infection 68 no. S1 (2014):108–14.
  7. B.L. Pearlman. “Protease Inhibitors for the Treatment of Chronic Hepatitis C Genotype-1 Infection: The New Standard of Care.” Lancet Infectious Diseases 12 no. 9 (2012):717–728.

Contributor

  • Nina Parker, (Shenandoah University), Mark Schneegurt (Wichita State University), Anh-Hue Thi Tu (Georgia Southwestern State University), Philip Lister (Central New Mexico Community College), and Brian M. Forster (Saint Joseph’s University) with many contributing authors. Original content via Openstax (CC BY 4.0; Access for free at https://openstax.org/books/microbiology/pages/1-introduction)


11.6: Drugs for Non-prokaryote Microbes - Biology

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Analysis of data from the Leukemia Precision-based Therapy (LEAP) Consortium revealed that many pediatric patients with leukemia may have genetic aberrations targetable with existing therapies clinical validation is awaited.

Treatment with navitoclax at a low dose (to limit toxicity) plus venetoclax led to complete remission in 60% of 47 adult and pediatric patients with relapsed or refractory acute lymphoblastic leukemia or lymphoblastic lymphoma in a phase I clinical trial.

Hypermutant replication repair–deficient cancers often harbored mutations in the RAS–MAPK pathway that could be targeted in vitro and in vivo with MEK inhibitors data from a small group of patients supports this notion.

Analyses of the tumor microenvironment in diffuse large B-cell lymphoma revealed the presence of four transcriptomically defined subtypes, each of which exhibited different responses to therapy and conferred different prognoses.


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Final Exam 12-08-20


​Dilution Tests

​As discussed, the limitations of the Kirby-Bauer disk diffusion test do not allow for a direct comparison of antibacterial potencies to guide selection of the best therapeutic choice. However, antibacterial dilution tests can be used to determine a particular drug’s minimal inhibitory concentration (MIC), the lowest concentration of drug that inhibits visible bacterial growth, and minimal bactericidal concentration (MBC), the lowest drug concentration that kills ≥99.9% of the starting inoculum. Determining these concentrations helps identify the correct drug for a particular pathogen. For the macrobroth dilution assay, a dilution series of the drug in broth is made in test tubes and the same number of cells of a test bacterial strain is added to each tube (Figure). The MIC is determined by examining the tubes to find the lowest drug concentration that inhibits visible growth this is observed as turbidity (cloudiness) in the broth. Tubes with no visible growth are then inoculated onto agar media without antibiotic to determine the MBC. Generally, serum levels of an antibacterial should be at least three to five times above the MIC for treatment of an infection.

The MIC assay can also be performed using 96-well microdilution trays, which allow for the use of small volumes and automated dispensing devices, as well as the testing of multiple antimicrobials and/or microorganisms in one tray (Figure). MICs are interpreted as the lowest concentration that inhibits visible growth, the same as for the macrobroth dilution in test tubes. Growth may also be interpreted visually or by using a spectrophotometer or similar device to detect turbidity or a color change if an appropriate biochemical substrate that changes color in the presence of bacterial growth is also included in each well.

The Etest is an alternative method used to determine MIC, and is a combination of the Kirby-Bauer disk diffusion test and dilution methods. Similar to the Kirby-Bauer assay, a confluent lawn of a bacterial isolate is inoculated onto the surface of an agar plate. Rather than using circular disks impregnated with one concentration of drug, however, commercially available plastic strips that contain a gradient of an antibacterial are placed on the surface of the inoculated agar plate (Figure). As the bacterial inoculum grows, antibiotic diffuses from the plastic strips into the agar and interacts with the bacterial cells. Because the rate of drug diffusion is directly related to concentration, an elliptical zone of inhibition is observed with the Etest drug gradient, rather than a circular zone of inhibition observed with the Kirby-Bauer assay. To interpret the results, the intersection of the elliptical zone with the gradient on the drug-containing strip indicates the MIC. Because multiple strips containing different antimicrobials can be placed on the same plate, the MIC of multiple antimicrobials can be determined concurrently and directly compared. However, unlike the macrobroth and microbroth dilution methods, the MBC cannot be determined with the Etest.

Figure 1. ​In a dilution test, the lowest dilution that inhibits turbidity (cloudiness) is the MIC. In this example, the MIC is 8 μg/mL. Broth from samples without turbidity can be inoculated onto plates lacking the antimicrobial drug. The lowest dilution that kills ≥99.9% of the starting inoculum is observed on the plates is the MBC. (credit: modification of work by Suzanne Wakim)

HR Welcomes Two to Guide Services and Planning

Human Resources will welcome two new staff members to its leadership team on Nov. 30.

Julie Stanley will become director of human resource services. In this role, she will be responsible for all HR services with departments at HMS, including employee and labor relations, recruitment and HR consulting. Stanley previously served as interim associate dean of human resources for the Faculty of Arts and Sciences.

Jeri Gardner will be joining as associate director of HR planning and program development. This position will play a critical role in the development of HR programs, including workplace engagement. She is currently the manager of HR planning and recruitment at Harvard Pilgrim Health Care.


Related Links

References: A Genetically Encoded Biosensor Reveals Location Bias of Opioid Drug Action. Stoeber M, Jullié D, Lobingier BT, Laeremans T, Steyaert J, Schiller PW, Manglik A, von Zastrow M. Neuron. 2018 May 5. pii: S0896-6273(18)30329-5. doi: 10.1016/j.neuron.2018.04.021. [Epub ahead of print]. PMID: 29754753.

Funding: NIH’s National Institute on Drug Abuse (NIDA) Canadian Institutes of Health Research and Swiss National Science Foundation.


Citation: Haldar K (2015) From Cell and Organismal Biology to Drugs. PLoS Pathog 11(6): e1005002. https://doi.org/10.1371/journal.ppat.1005002

Published: June 25, 2015

Copyright: © 2015 Kasturi Haldar. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Funding: The author received no specific funding for this article.

Competing interests: KH is co-EIC of PLOS Pathogens. She cofounded and serves as Chief Scientific Officer of NP-C Therapeutics LLC. She is a member of the Expert Scientific Advisory Board of Medicines for Malaria Venture. She adheres to all PLOS policies on sharing data and materials.

Because malaria takes a major toll on human health globally, the focus on how to treat it and reduce the malaria burden is understandable. But I became interested in studying the malaria parasite because of its intracellular niche in the mature red blood cell. This is a specialized host cell designed to carry oxygen to tissues, explaining its high hemoglobin content (which also confers the red color) and deformability needed to travel through the smallest of capillaries. But these cells are dead ends, without a nucleus and many cellular capacities (such as synthesis of new nucleic acids, proteins and lipids, and nutrient uptake) that pathogens need from their host cells. Also, the mature red blood cell does not internalize or reorganize its surface membrane, a process critical for host infection by most microbes. No self-respecting virus would infect a red blood cell and most bacteria, parasites, and fungi do not. And yet malaria parasites are large pathogens (

1–2 micron) that infect a relatively small-diameter dead end host cell (

7 micron). You don’t have to be a rocket scientist to infer that the parasite must play an active role in the infection process because the host cell couldn’t—but how did it happen?

I decided that secretion from the parasite to the red cell must be very important and my lab would broadly study the parasite’s Golgi structure, because in most cells, this compartment makes important decisions on what cellular cargo is secreted. Moreover, while the parasite needed to make these secretion decisions for destinations bounded by its own surface membrane as well as those beyond in the red cell, there was no evidence of Golgi “stacks” (characteristic of this organelle) in this pathogen.

The first three years for my lab in the early 1990s were a hard slog, with a pile of negative results, because most molecular Golgi functions found in other cells are absent in the blood stage malaria parasite. Just as deep anxiety began to set in that this was the wrong question to ask, the onion began to unpeel productively. We discovered that the parasite was not just secreting cargo to the red blood cell it was also releasing an entire subcompartment of its rather rudimentary Golgi. There has been no looking back since then, because the parasite commits a large proportion of its genetic composition to secreting and remodeling the red cell—a fact that became a certainty after 2002 when the first malaria parasite genome was sequenced. This new understanding didn’t immediately eliminate or eradicate malaria, but it accelerated the linking of fundamental biology and mechanisms of pathogenesis in labs like mine to the discovery of new therapeutic strategies (since the parasite is increasingly drug resistant). It also eventually resulted in the establishment of collaborations with major pharmaceutical companies, e.g., Eli Lilly & Co, and private product partnerships, e.g., the Medicines for Malaria Venture.

Our recent work on rare genetic disorders was initiated almost 20 years after we began our studies in malaria. But here again, we started in basic discovery, using mouse models of disease. Driven by the invariably fatal outcome that faces the small community of patients struck by the rare neurological disease, Niemann-Pick, type C (NPC), and armed with genomics, we repurposed existing drugs to improve the treatment of this disease. This effort has led to the establishment of a small pharmaceutical company (NP-C Therapeutics, LLC), the goal of which is to develop treatments for NPC and other neurological disorders, because monogenetic rare disorders, such as NPC, provide powerful portals into the more prevalent multigenic disorders, such as Alzheimer’s and Parkinson’s diseases. This approach may also provide insights into the recent outbreak and spread of Ebola, because the virus uses the NPC1 protein to infect host cells (and deficiency in NPC1 protects against infection).

Not every scientific discovery from basic research ensures translation into a therapy. But there have been more therapies realized from basic research than by the emerging trends of directed translational engagement in the absence of evidence-based research. Investment in a broad range of basic research (because it is important to query scientific problems in many ways) enables collective preparedness for new translational challenges that defy political agendas and fearmongering for partisan gain. This outcome is compelling justification for national and international agencies to prioritize unfettered discovery and basic research. Failure to do this will jeopardize future employment, training, and education at the university, college, and high school levels. Therefore, development of a new generation of researchers, trained in a virtuous cycle of rigorous scientific query and hard work, is imperative to sustain our overarching expectations for this upcoming century.


11.6: Drugs for Non-prokaryote Microbes - Biology

Show all 20 random questions

  1. ? produces an antiseptic liquid when irritated
  2. ? acts as a barrier to germs and produces an antiseptic oil
  3. ? sticky mucous traps microbes which is removed by cilia cells
  4. ? platelets produce clots which dry to form a barrier to germs
  5. ? white cells surround and destroy microbes
  1. ? produces an antiseptic liquid when irritated
  2. ? acts as a barrier to germs and produces an antiseptic oil
  3. ? sticky mucous traps microbes which is removed by cilia cells
  4. ? platelets produce clots which dry to form a barrier to germs
  5. ? contains acid that kills most harmful bacteria
  1. ? white cells surround and destroy microbes
  2. ? acts as a barrier to germs and produces an antiseptic oil
  3. ? sticky mucous traps microbes which is removed by cilia cells
  4. ? platelets produce clots which dry to form a barrier to germs
  5. ? contains acid that kills most harmful bacteria
  1. ? produces an antiseptic liquid when irritated
  2. ? acts as a barrier to germs and produces an antiseptic oil
  3. ? sticky mucous traps microbes which is removed by cilia cells
  4. ? platelets produce clots which dry to form a barrier to germs
  5. ? contains acid that kills most harmful bacteria
  1. ? produces an antiseptic liquid when irritated
  2. ? acts as a barrier to germs and produces an antiseptic oil
  3. ? sticky mucous traps microbes which is removed by cilia cells
  4. ? contains acid that kills most harmful bacteria
  5. ? white cells surround and destroy microbes
  1. ? contains acid that kills most harmful bacteria
  2. ? acts as a barrier to germs and produces an antiseptic oil
  3. ? sticky mucous traps microbes which is removed by cilia cellsbes which is moved by cilia cells
  4. ? platelets produce clots which dry to form a barrier to germs
  5. ? white cells surround and destroy microbes
  1. ? it has a protein coat, has genes, no cytoplasm, can only reproduce in living 'host' cells and damages them, not destroyed by antibiotics, extremely small (many cannot be seen even with a powerful optical microscope)
  2. ? it has a cell wall (not cellulose) and cell membrane, has genes and cytoplasm, no nucleus, produces toxins, can reproduce outside living cells and is destroyed by antibiotics
  3. ? it is a single cell or cellular filaments with nucleus containing genes surrounded by cytoplasm but does not contain chlorophyl
  1. ? it has a protein coat, has genes, no cytoplasm, can only reproduce in living 'host' cells and damages them, not destroyed by antibiotics, extremely small (many cannot be seen even with a powerful optical microscope)
  2. ? it has a cell wall (not cellulose) and cell membrane, has genes and cytoplasm, no nucleus, produces toxins, can reproduce outside living cells and is destroyed by antibiotics
  3. ? it is a single cell or cellular filaments with nucleus containing genes surrounded by cytoplasm but does not contain chlorophyl
  1. ? it has a protein coat, has genes, no cytoplasm, can only reproduce in living 'host' cells and damages them, not destroyed by antibiotics, extremely small (many cannot be seen even with a powerful optical microscope)
  2. ? it has a cell wall (not cellulose) and cell membrane, has genes and cytoplasm, no nucleus, produces toxins, can reproduce outside living cells and is destroyed by antibiotics
  3. ? it is a single cell or cellular filaments with nucleus containing genes surrounded by cytoplasm but does not contain chlorophyl
  1. ? injection of dead or weakened micro-organism to stimulate production of antibodies
  2. ? the result of a micro-organism entering the body and causing disease
  3. ? kills, or prevents the growth of bacteria on external parts of the body
  4. ? kills, or prevents the growth of bacteria in the body
  5. ? a micro-organism that can cause a disease
  1. ? injection of dead or weakened micro-organism to stimulate production of antibodies
  2. ? the result of a micro-organism entering the body and causing disease
  3. ? kills, or prevents the growth of bacteria on external parts of the body
  4. ? kills, or prevents the growth of bacteria in the body
  5. ? a protein made by white blood cells that can help destroy microbes
  1. ? injection of dead or weakened micro-organism to stimulate production of antibodies
  2. ? the result of a micro-organism entering the body and causing disease
  3. ? kills, or prevents the growth of bacteria on external parts of the body
  4. ? kills, or prevents the growth of bacteria in the body
  5. ? a protein made by white blood cells that can help destroy microbes
  1. ? a protein made by white blood cells that can help destroy microbes
  2. ? the result of a micro-organism entering the body and causing disease
  3. ? a protein made by white blood cells that can help destroy microbes
  4. ? kills, or prevents the growth of bacteria in the body
  5. ? a micro-organism that can cause a disease
  1. ? injection of dead or weakened micro-organism to stimulate production of antibodies
  2. ? a protein made by white blood cells that can help destroy microbes
  3. ? kills, or prevents the growth of bacteria on external parts of the body
  4. ? kills, or prevents the growth of bacteria in the body
  5. ? a micro-organism that can cause a disease
  1. ? injection of dead or weakened micro-organism to stimulate production of antibodies
  2. ? the result of a micro-organism entering the body and causing disease
  3. ? kills, or prevents the growth of bacteria on external parts of the body
  4. ? kills, or prevents the growth of bacteria in the body
  5. ? a protein made by white blood cells that can help destroy microbes
  1. ? 2.0g sugar, 20 o C
  2. ? 3.5g sugar, 35 o C
  3. ? 2.0g sugar, 35 o C
  4. ? 3.5g sugar, 20 o C
  1. ? 2.0g sugar, 20 o C
  2. ? 3.5g sugar, 35 o C
  3. ? 2.0g sugar, 35 o C
  4. ? 3.5g sugar, 20 o C

You can grow micro-organisms in a __(1)__ containing a gelatinous layer of __(2)__ mixed with __(3)__ to feed on. The __(4)__ are spread across the gel using a __(5)__ wire loop.

Which word(s) is/are missing from __(1)__? [8c-20]

You can grow micro-organisms in a __(1)__ containing a gelatinous layer of __(2)__ mixed with __(3)__ to feed on. The __(4)__ are spread across the gel using a __(5)__ wire loop.

Which word(s) is/are missing from __(2)__? [8c-21]

You can grow micro-organisms in a __(1)__ containing a gelatinous layer of __(2)__ mixed with __(3)__ to feed on. The __(4)__ are spread across the gel using a __(5)__ wire loop.

Which word(s)) is/are missing from __(3)__? [8c-22]

You can grow micro-organisms in a __(1)__ containing a gelatinous layer of __(2)__ mixed with __(3)__ to feed on. The __(4)__ are spread across the gel using a __(5)__ wire loop.

Which word(s) is/are missing from __(4)__? [8c-23]

You can grow micro-organisms in a __(1)__ containing a gelatinous layer of __(2)__ mixed with __(3)__ to feed on. The __(4)__ are spread across the gel using a __(5)__ wire loop.

Which word(s) is/are missing from __(5)__? [8c-24]

  1. ? antibiotics like penicillin, stop bacteria reproducing
  2. ? viruses can't cause diseases
  3. ? white blood cells can't kill harmful micro-organisms
  4. ? antibodies in your blood help form a protective scab over a cut
  5. ? while still in the womb, a baby cannot get antibodies from its mother
  1. ? antibiotics like penicillin, stop viruses reproducing
  2. ? viruses can cause diseases
  3. ? white blood cells can't kill harmful micro-organisms
  4. ? antibodies in your blood help form a protective scab over a cut
  5. ? while still in the womb, a baby cannot get antibodies from its mother
  1. ? antibiotics like penicillin, stop viruses reproducing
  2. ? viruses can't cause diseases
  3. ? white blood cells can kill harmful micro-organisms
  4. ? antibodies in your blood help form a protective scab over a cut
  5. ? while still in the womb, a baby cannot get antibodies from its mother
  1. ? antibiotics like penicillin, stop viruses reproducing
  2. ? viruses can't cause diseases
  3. ? white blood cells can't kill harmful micro-organisms
  4. ? platelets in your blood help form a protective scab over a cut
  5. ? while still in the womb, a baby cannot get antibodies from its mother
  1. ? antibiotics like penicillin, stop viruses reproducing
  2. ? viruses can't cause diseases
  3. ? white blood cells can't kill harmful micro-organisms
  4. ? antibodies in your blood help form a protective scab over a cut
  5. ? while still in the womb, a baby can get antibodies from its mother
  1. ? drinking water is treated with chlorine before domestic use
  2. ? the result of being injected with a dead or weakened form of a micro-organism to stimulate antibody production
  3. ? using yeast and sugar solution to make alcohol
  4. ? milk is treated to remove some fat to make it semi-skimmed
  1. ? drinking water is treated with chlorine before domestic use
  2. ? the result of being injected with a dead or weakened form of a micro-organism to stimulate antibody production
  3. ? using yeast and sugar solution to make alcohol
  4. ? milk is heated to a high temperature for a short time before selling to customer
  1. ? drinking water is treated with chlorine before domestic use
  2. ? the result of being injected with a dead or weakened form of a micro-organism to stimulate antibody production
  3. ? using yeast and sugar solution to make alcohol
  4. ? milk is heated to a high temperature for a short time before selling to customer
  1. ? drinking water is treated with chlorine before domestic use
  2. ? the result of being injected with a dead or weakened form of a micro-organism to stimulate antibody production
  3. ? using yeast and sugar solution to make alcohol
  4. ? milk is heated to a high temperature for a short time before selling to customer

Very small living things that can only be seen with a __(1)__ and are called __(2)__. Some are __(3)__ like __(4)__ used in breadmaking. However, others are __(5)__ causing diseases like __(6)__.

Which missing word is __(1)__? [8c-34]

  1. ? microscope
  2. ? microbes
  3. ? useful
  4. ? yeast
  5. ? harmful
  6. ? cholera

Very small living things that can only be seen with a __(1)__ and are called __(2)__. Some are __(3)__ like __(4)__ used in breadmaking. However, others are __(5)__ causing diseases like __(6)__.

Which missing word is __(2)__? [8c-35]

  1. ? microscope
  2. ? microbes
  3. ? useful
  4. ? yeast
  5. ? harmful
  6. ? cholera

Very small living things that can only be seen with a __(1)__ and are called __(2)__. Some are __(3)__ like __(4)__ used in breadmaking. However, others are __(5)__ causing diseases like __(6)__.

Which missing word is __(3)__? [8c-36]

  1. ? microscope
  2. ? microbes
  3. ? useful
  4. ? yeast
  5. ? harmful
  6. ? cholera

Very small living things that can only be seen with a __(1)__ and are called __(2)__. Some are __(3)__ like __(4)__ used in breadmaking. However, others are __(5)__ causing diseases like __(6)__.

Which missing word is __(4)__? [8c-37]

  1. ? microscope
  2. ? microbes
  3. ? useful
  4. ? yeast
  5. ? harmful
  6. ? cholera

Very small living things that can only be seen with a __(1)__ and are called __(2)__. Some are __(3)__ like __(4)__ used in breadmaking. However, others are __(5)__ causing diseases like __(6)__.

Which missing word is __(5)__? [8c-38]

  1. ? microscope
  2. ? microbes
  3. ? useful
  4. ? yeast
  5. ? harmful
  6. ? cholera

Very small living things that can only be seen with a __(1)__ and are called __(2)__. Some are __(3)__ like __(4)__ used in breadmaking. However, others are __(5)__ causing diseases like __(6)__.


Euryarchaeota

​The phylum Euryarchaeota includes several distinct classes. Species in the classes Methanobacteria, Methanococci, and Methanomicrobia represent Archaea that can be generally described as methanogens. Methanogens are unique in that they can reduce carbon dioxide in the presence of hydrogen, producing methane. They can live in the most extreme environments and can reproduce at temperatures varying from below freezing to boiling. Methanogens have been found in hot springs as well as deep under ice in Greenland. Some scientists have even hypothesized that methanogens may inhabit the planet Mars because the mixture of gases produced by methanogens resembles the makeup of the Martian atmosphere. 4

Methanogens are thought to contribute to the formation of anoxic sediments by producing hydrogen sulfide, making “marsh gas.” They also produce gases in ruminants and humans. Some genera of methanogens, notably Methanosarcina, can grow and produce methane in the presence of oxygen, although the vast majority are strict anaerobes.

The class Halobacteria (which was named before scientists recognized the distinction between Archaea and Bacteria) includes halophilic (“salt-loving”) archaea. Halobacteria require a very high concentrations of sodium chloride in their aquatic environment. The required concentration is close to saturation, at 36% such environments include the Dead Sea as well as some salty lakes in Antarctica and south-central Asia. One remarkable feature of these organisms is that they perform photosynthesis using the protein bacteriorhodopsin, which gives them, and the bodies of water they inhabit, a beautiful purple color (Figure 2).

Figure 2. Halobacteria growing in these salt ponds gives them a distinct purple color. (credit: modification of work by Tony Hisgett)​

​Notable species of Halobacteria include Halobacterium salinarum, which may be the oldest living organism on earth scientists have isolated its DNA from fossils that are 250 million years old. 5 Another species, Haloferax volcanii, shows a very sophisticated system of ion exchange, which enables it to balance the concentration of salts at high temperatures.

​FINDING A LINK BETWEEN ARCHAEA AND DISEASE

​Archaea are not known to cause any disease in humans, animals, plants, bacteria, or in other archaea. Although this makes sense for the extremophiles, not all archaea live in extreme environments. Many genera and species of Archaea are mesophiles, so they can live in human and animal microbiomes, although they rarely do. As we have learned, some methanogens exist in the human gastrointestinal tract. Yet we have no reliable evidence pointing to any archaean as the causative agent of any human disease.

Still, scientists have attempted to find links between human disease and archaea. For example, in 2004, Lepp et al. presented evidence that an archaean called Methanobrevibacter oralis inhabits the gums of patients with periodontal disease. The authors suggested that the activity of these methanogens causes the disease. 6 However, it was subsequently shown that there was no causal relationship between M. oralis and periodontitis. It seems more likely that periodontal disease causes an enlargement of anaerobic regions in the mouth that are subsequently populated by M. oralis. 7

There remains no good answer as to why archaea do not seem to be pathogenic, but scientists continue to speculate and hope to find the answer.


Watch the video: Εισαγωγή στο κύτταρο (July 2022).


Comments:

  1. Enea

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  2. Duhn

    just what do you have to do in this case?

  3. Grolar

    Many thanks for the help in this question, now I will not commit such error.

  4. Mooguzil

    Are there more options?

  5. Elvyn

    No time for love now, fin. crisis is a serious thing



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