Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens

Sophie Brinster et al. Nature 458, 83-86 (5 March 2009)

Speaker: Po-Pin Hung (洪伯斌)                       Time: 14:00~15:00, Oct. 14, 2009

Commentator: Lien-I Hor (何漣漪老師)           Place: Room 601

Abstract：

        Inconsistent consequence exists between the experiments executed in vitro and actual phenomenon in vivo, especially when the experiment designs have too much artificial bias. These include inappropriate simulation (the infection dose, the portal of entry, the inadequate observation period), arbitrary time flame between inoculations of infectious agents and the time to treat with reagents subsequently, and excessive extrapolation based upon the defined conclusion. This article, although not perfect in theory, makes the attempt to illustrate the discrepancy actually between the experiment in vitro and animal study in vivo. The authors investigate the effect of FASII inhibitors (with equivalent compounds: cerulenin and triclosan; the former is the well-known antifungal agent aimed at fatty acid biosynthesis in fungi, and the latter is a kind of antiseptics) in FASII-knock-out strains of S. agalactiae cultivated in the fatty-acid-free medium with or without supplement of fatty acids (with Tween 80 or human saliva). The results of the study imply the discrepant conclusion that the FASII inhibitors may have no anticipated effect on the bacteria in interest when they are used to treat infections caused by Gram-positive bacteria. The study and the 2^nd study in Reference below show that the condition in vivo may abolish/diminish the expected effect and evoke the potential effect, respectively. This will make us know that we should contemplate applying the findings in vitro onto the actual condition in vivo.

Abbreviation

        FASII, type II fatty acid synthesis

References：

1.   Yamamoto, Y. et al. The group B streptococcus NADH oxidase Nox-2 is involved in fatty acid biosynthesis during aerobic growth and contributes to virulence. Mol. Microbiol. 62, 772–785

2.   Scortti, M. et al. Coexpression of virulence and fosfomycin susceptibility in Listeria: molecular basis of an antimicrobial in vitro-in vivo paradox. Nature Med. 12, 515–517 (2006)