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.