The forgotten Gram-negative bacilli: what genetic determinants are telling us about the spread of antibiotic resistance.
Gram-negative bacilli have become increasingly resistant to antibiotics over the past 2 decades due to selective pressure from the extensive use of antibiotics in the hospital and community. In addition, these bacteria have made optimum use of their innate genetic capabilities to extensively mutate structural and regulatory genes of antibiotic resistance factors, broadening their ability to modify or otherwise inactivate antibiotics in the cell. The great genetic plasticity of bacteria have permitted the transfer of resistance genes on plasmids and integrons between bacterial species allowing an unprecedented dissemination of genes leading to broad-spectrum resistance. As a result, many Gram-negative bacilli possess a complicated set of genes encoding efflux pumps, alterations in outer membrane lipopolysaccharides, regulation of porins and drug inactivating enzymes such as beta-lactamases, that diminish the clinical utility of today's antibiotics. The cross-species mobility of these resistance genes indicates that multidrug resistance will only increase in the future, impacting the efficacy of existing antimicrobials. This trend toward greater resistance comes at a time when very few new antibiotics have been identified capable of controlling such multi-antibiotic resistant pathogens. The continued dissemination of these resistance genes underscores the need for new classes of antibiotics that do not possess the liability of cross-resistance to existing classes of drugs and thereby having diminished potency against Gram-negative bacilli.
Gootz
Thomas D
TD
Pfizer Global Research and Development, Department of Antibiotics, Immunology and Cancer, MS 220-2301, Eastern Point Road, Groton, CT 06340, USA. Thomas.d.gootz@pfizer.com
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000235:genetics; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics
D000900:Anti-Bacterial Agents; D026901:Membrane Transport Proteins