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Antibiotic Resistance in Microbes A few microbes to be concerned about How some antibiotics and Antimicrobials work Resistance mechanisms Some factors involved in resistance Reversing resistance Conclusions References
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A Few Microbes to Be Concerned About Mycobacterium tuberculosis: tuberculosis Resistant to: streptomycin, Pyrazinamide, Ethambutol, isoniazid, and rifampin Staphylococcus aureus: Staph infections Resistant to: penicillin, erythromycin, Gentomycin MRSA and VRSA Salmonella typhimurium:: typhoid fever Resistant to: Ampicillin, Chloramphenicol, streptomycin, Sulfanamides, tetracycline
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A Few More Microbes... Yersinia pestis : plague - multi resistant Treponema palladium : syphilis - multi resistant Neisseria gonorrhoeae: Gonorrhoeae - multi resistant
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A Few More Microbes... Campylobacter jejuni : Campylobacter - Multi Resistant Shigella dysenteriae : Dysentery - Multi Resistant Eschericia Coli (including E. coli 0157 : H7) : Hemorrhagic Diarrhea, Kidney failure - Multi Resistant
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How Some Antibiotics Work Penicillin G (Gram + Bacteria) : B lactam ring binds to transpeptidase inhibiting cross-linking of cell wall resulting in cell lysis Aminoglycosides : Streptomycin, Gentomycin Inhibits protein synthesis on 30s ribosomal subunit Tetracyclines ( Broad Spectrum - Gram - and Gram + ) : Inhibits protein synthesis on 30s ribosomal subunit Macrolide Antibiotics : Erythromycin, Spiramycin Inhibits protein synthesis on 50s ribosomal subunit
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How Some Antimicrobials Work Sulfa Drugs : Sulfanilamide Blocks synthesis of folic acid Quinolones : Norflaxin, Ciproflaxin (Broad Spectrum) Prevents bacterial DNA gyrase from supercoiling bacterial DNA
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Resistance Mechanisms B-lactamases : B-lactamases cleave B-lactam rings from penicillin Modification of Drugs : Some enzymes have the ability to phosphorylate, adenylate, or acetylate antibiotics-chloramphenicols and aminoglycosides
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Resistance Mechanisms Efflux Pumps and Prevention of Uptake : Enzymes actively pump out drugs or the drug is not taken into the cell at all-tetracycline Enzymes with Altered Shapes : Enzyme proteins with altered shapes are produced so that the drug no longer fits to inhibit-Rifampin and Quinolones
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Some Factors Involved in Resistance Chromosomal Resistance : Tends to involve modification of the target drug R-Plasmids (R-Factors) : Tend to involve inactivation of drugs Can be shared with many different strains and species Multi-resistant R-plasmids have several genes which encode for different enzymes
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Some Factors Involved in Resistance Antibiotic Treatment : Taking antibiotics can clear out naturally occurring gut flora Multiple Resistance From One Antibiotic : Some studies have shown that after exposure to only one antibiotic, resistance to multiple antibiotics can be produced
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Reversing Resistance Natural Selection : Many resistant strains do not compete as well as non-resistant strains When not artificially selected for, resistant microbes tend to return to naturally low levels in populations
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Conclusion Multi-Resistant microbes are a major concern Come from many places in the environment Microbes have many ingenious ways of dealing with antibiotics Resistance is generally a reversible process
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References Ackerman, Jennifer. Food: How Safe? National Geographic Magazine, National Geographic Society, May 2002, p.2-p.31. Bryan, L.E., Bacterial resistance and susceptibility to chemotheraputic agents. Cambridge University Press, Cambridge, 1982. Harrison, Polly F., Lederberg, Joshua, et.al. ANTIMICROBIAL RESISTANCE: Issues and Options-Workshop report. Forum on Emerging Infections, Institute of Medicine. National Academy Press, Washington, D.C. 1998 Moore, Pete, BSc, PhD. Killer Germs: Rogue Diseases of the Twenty First Century. Carlton Books Limited, London, 2001. Reichman, Lee B., M.D., M.P.H., Tanne, Janice Hopkins. Timebomb: The Global Epidemic of Multi-Resistant Tuberculosis. McGraw-Hill, New York, 2002. Weiss, Rick. War on Disease: Deadly New Threats. National Geographic Magazine, National Geographic Society, February 2002. P.4-p.31.
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