The potential of bacterial fatty acid biosynthetic enzymes as a source of novel antibacterial agents.
Bacteria can produce new progeny in only 20 minutes (500,000 times faster than humans), enabling them to rapidly mutate and evolve ingenious methods to outwit just about all of the currently available antibiotics. These mechanisms can then disseminate rapidly through bacterial populations via transmissible pieces of DNA such as transposons, integrons and plasmids. This leads to resistance mechanisms becoming geographically dispersed and has resulted in the overall decrease in the susceptibility of microorganisms to antibiotics that used to be highly efficacious. There is an obvious need for new antibiotics that kill bacteria via novel mechanisms not previously exploited by existing agents; this will provide new generations of antibiotics unlikely to be compromised by preexisting resistance mechanisms. The fatty acid biosynthetic pathway is an essential metabolic process in bacteria and presents several novel targets for antibiotic development.
Payne
David J
DJ
Department of Microbiology, GlaxoSmithKline, Collegeville, Pennsylvania, USA. David_J_Payne@gsk.com
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D016680:Genome, Bacterial; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000235:genetics
D000900:Anti-Bacterial Agents; D000962:Antimalarials; D005227:Fatty Acids; D010088:Oxidoreductases; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D064429:Fatty Acid Synthases