A cell wall damage response mediated by a sensor kinase/response regulator pair enables beta-lactam tolerance

Tobias Dörr, Laura Alvarez, Fernanda Delgado, Brigid M. Davis, Felipe Cava, and Matthew K. Waldor. PNAS. January 12, 2016. vol. 113. no. 2

Speaker: Yi-Ching Chiu (邱意晴)                                Time: 15:00~16:00, Apr. 6, 2016

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

Abstract:

The cell wall is an essential protective structure for bacteria, and the enzymes required for its biogenesis are the targets for many potent antibiotics. [1] In this study, the authors described a signaling system (the histidine kinase/response regulator pair WigKR) that helps Vibrio cholerae to survive exposure to antibiotics targeting cell wall synthesis in vitro and during infection. The authors have previously shown that Vibrio cholerae, is intrinsically tolerant to antibiotics targeting cell wall synthesis. Upon exposure to cell wall synthesis inhibitors, V. cholerae decreased its cell wall and forms viable, non-dividing spheres, which readily revert to the normal rod shape upon removal of the antibiotic. [2]

A TnSeq-based screen for V. cholerae factors required for recovery from penicillin exposure revealed that insertions in WigK and WigR were underrepresented in a transposon insertion library following treatment with penicillin. The authors confirmed wigKR locus was required for V.cholerae’s tolerance to inhibitors of cell wall synthesis. Also, they found the activation of WigR led to increased expression of genes required for cell wall synthesis and enabled the pathogens to recover from the spherical non-dividing state induced by antibiotics. Moreover, the deletion or overexpression of WigR caused changes in cell width, suggesting that the WigKR two-component system modulates cell wall homeostasis under normal growth conditions in the absence of antibiotics. Collectively, these findings implicate WigKR as a regulator of cell wall homeostasis in response to antibiotics and likely during normal growth as well.

References:

1.     Schneider T, Sahl HG (2010) An oldie but a goodie: Cell wall biosynthesis as antibiotic target pathway. Int J Med Microbiol 300(2-3):161–169.

2.     Dörr T, Davis BM, Waldor MK (2015) Endopeptidase-mediated beta lactam tolerance. PLoS Pathog 11(4):e1004850.