Nonlethal Drugs

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Science  10 Apr 2009:
Vol. 324, Issue 5924, pp. 151
DOI: 10.1126/science.324.5924.151a

The repeated appearance of bacteria that have developed resistance to the latest generation of antibiotics has fueled the search for other kinds of anti-infective drugs. Gutierrez et al. have targeted quorum sensing, the process by which bacteria signal to each other through molecules called autoinducers. These signals coordinate gene expression across individuals in a community, can enhance survival, and in the case of pathogenic bacteria, regulate virulence. The bacterial enzyme 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is involved in the production of autoinducers. Transition-state analogs that inhibited MTAN activity in vitro also inhibited the production of autoinducers in vivo but did not affect the growth of Vibrio cholerae or Escherichia coli. This sensitivity persisted during growth for 26 generations in the presence of the inhibitor; furthermore, a reduction in the formation of biofilms—a protective lifestyle for bacteria—was also observed. MTAN is expressed by other bacterial pathogens, so attacking virulence in this nonlethal manner may delay the development of drug resistance. — LC

Nat. Chem. Biol. 5, 251 (2009).

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