Scientific Seminar Series: Malonyl-CoA and (p)ppGpp set the pace for Staphylococcus aureus resistance and bypass of FASII inhibitors | Shiv Nadar University
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Scientific Seminar Series: Malonyl-CoA and (p)ppGpp set the pace for Staphylococcus aureus resistance and bypass of FASII inhibitors

Event Date: 
Tuesday, January 8, 2019 - 00:00

‘Scientific Seminar Series’

Research Seminar

 AMIT PATHANIA, PhD

Biochemistry & Molecular Genetics

Micalis Institute, INRA, AgroParisTech,

Université Paris-Saclay, Jouy-en-Josas,

France.

 

 ‘Malonyl-CoA and (p)ppGpp set the pace for Staphylococcus aureus resistance and bypass of  FASII inhibitors’

Fatty acid biosynthesis (FASII) enzymes are considered as valid targets for antimicrobial drug development against the major gram-positive pathogen Staphylococcus aureus. However, we showed that the FASII inhibitor triclosan can be overcome in fatty acid environments containing host serum. In this situation, S. aureus undergoes a 10-12 h latency period during which expression is reprogrammed. After latency, S. aureus resumes growth in a fully adapted state, such that cells use exclusively exogenous fatty acids. We investigated the role of two intracellular cofactors, (p)ppGpp and malonyl-CoA, in the latent and outgrowth phases of S. aureus adaptation to FASII inhibitors. High amount of (p)ppGpp has a metabolic signature: induction of high expression of genes involved in amino acid biosynthesis and transport while suppression of the genes involved in replication and ribosome biogenesis (Tobias et al, 2012). Proteomics analysis of S. aureus grown in triclosan supplemented medium unfolds that bacteria exhibit a partial overlapped (p)ppGpp response in early dormancy. Metabolic sensors based on transcriptional fusions were designed to evaluate metabolite levels during adaptation. Our results reveal that (p)ppGpp levels are transiently increased during dormancy, but then return to background level once cells are adapted. Malonyl-CoA pools are inversely affected: levels are low in latency and increased during adaptation. We also observed that (p)ppGpp induction leads to decreased malonyl-CoA levels, indicating that concentrations of these factors are inversely expressed. Interestingly, S. aureus incorporates exogenous fatty acids more efficiently when ppGpp levels are low. Interestingly, S. aureus malonyl-CoA and (p)ppGpp levels in dormant and adapted phases follow the same expression pattern as that in stationary and exponential phase cells respectively. We propose that malonyl-CoA and (p)ppGpp may work antagonistically for the final decision of the cells either to be in the dormant (non-dividing) or adaptive phase (dividing).

Tuesday 08, Jan 2019
Date- 8 January 2019 (Tuesday) Venue- D330 Seminar room Time- 1-2 PM

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