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
A Few Microbes to Be Concerned About
Mycobacterium tuberculosis: tuberculosisResistant to: streptomycin, Pyrazinamide, Ethambutol, isoniazid, and rifampin
Staphylococcus aureus: Staph infectionsResistant to: penicillin, erythromycin, GentomycinMRSA and VRSA
Salmonella typhimurium:: typhoid feverResistant to: Ampicillin, Chloramphenicol, streptomycin, Sulfanamides, tetracycline
A Few More Microbes...
Yersinia pestis : plague - multi resistant
Treponema palladium : syphilis - multi resistant
Neisseria gonorrhoeae: Gonorrhoeae - multi
resistant
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
How Some Antibiotics WorkPenicillin 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, SpiramycinInhibits protein synthesis on 50s ribosomal subunit
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
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
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
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
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
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
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
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.