From Sherris Medical Microbiology, 4th edition, McGraw Hill, 2004 Inhibitors of Nucleic Acid SynthesisPhysiological Mechanisms of Bacterial Resistance to Antibiotics 1. Outer Membrane Proteins These proteins restrict entry of antibiotics anyway but mutations increase resistance even more 2. Inactivation of Antibiotics Example--beta lactamase. cleaves beta lactam ring . Clavulanic or Sulfbactim inhibit beta lactamase 3. Modification of Antibiotic Enzymes that modify antibiotics like streptomycin by adding phosphate adenyl or acetyl groups. The result is reduced transport through outer membrane 4. Efflux of Antibiotic Proteins in the membrane that pump out the antibiotic as fast as it comes in. Ex. Pumps that excrete tetraclycine 5. Modification of Target Altered ribosomal subunit or penicillin binding proteinOrigin and transmission of resistance The genes for drug resistance are present on both the bacterial chromosome and plasmids (small circular DNA molecules that can exist separate from the chromosome or be integrated into it). Often on the chromosome, virulence genes exist on segments called pathogenicity islands. e.g. genes that code for invasion, capsules, toxin drug resistance may be on the same gene segment. The virulence genes can be transmitted among the bacteria by genetic exchange mechanisms: • Bacteriophage • Conjugation • TransposonsTypes of Vaccines Attenuated • Used extensively--polio, BCG, measles, mumps • Achieved by passing the organism repeatedly in vitro to reduce it virulence; or by introducing a mutation. Inactivated • Organism killed by heat or chemicals • Less effective than attenuated versions • High potential for side effects Purified Macromolecules • Inactivated Toxins (toxoids)--tetanus, diptheria; some of the most successful of all vaccines • Capsular Polysaccharides--pneumoccal vaccine • Recombinant Surface Antigens--Hepatitis B--first recombinant vaccine for humans; put on plasmid and mass produced in yeast; 95% effective DNA • Latest form of vaccination; highly promising; inject DNA encoding a viral inmmunogen into muscle • Leads to development of antibody responses and cytotoxic T cells that allows the mice to reject a later challenge with the whole virus • Generally thought of as safe • Questions remain • No risk of infection because it carries a single gene Plantabodies • Antibodies made in plants such as potatoes or
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