A Systematic Evaluation of the Two-Component Systems Network Reveals That ArlRS Is a Key Regulator of Catheter Colonization by Staphylococcus aureus

Two-component systems (TCS) are modular signal transduction pathways that allow cells to adapt to prevailing environmental conditions by modifying cellular physiology. has 16 TCSs to adapt to the diverse microenvironments encountered during its life cycle, including host tissues and implanted medica...

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Published inFrontiers in microbiology Vol. 9; p. 342
Main Authors Burgui, Saioa, Gil, Carmen, Solano, Cristina, Lasa, Iñigo, Valle, Jaione
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 07.03.2018
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Summary:Two-component systems (TCS) are modular signal transduction pathways that allow cells to adapt to prevailing environmental conditions by modifying cellular physiology. has 16 TCSs to adapt to the diverse microenvironments encountered during its life cycle, including host tissues and implanted medical devices. is particularly prone to cause infections associated to medical devices, whose surfaces coated by serum proteins constitute a particular environment. Identification of the TCSs involved in the adaptation of to colonize and survive on the surface of implanted devices remains largely unexplored. Here, using an catheter infection model and a collection of mutants in each non-essential TCS of , we investigated the requirement of each TCS for colonizing the implanted catheter. Among the 15 mutants in non-essential TCSs, the mutant exhibited the strongest deficiency in the capacity to colonize implanted catheters. Moreover, the mutant was the only one presenting a major deficit in PNAG production, the main exopolysaccharide of the biofilm matrix whose synthesis is mediated by the locus. Regulation of PNAG synthesis by ArlRS occurred through repression of IcaR, a transcriptional repressor of operon expression. Deficiency in catheter colonization was restored when the mutant was complemented with the operon. MgrA, a global transcriptional regulator downstream ArlRS that accounts for a large part of the regulon, was unable to restore PNAG expression and catheter colonization deficiency of the mutant. These findings indicate that ArlRS is the key TCS to biofilm formation on the surface of implanted catheters and that activation of PNAG exopolysaccharide production is, among the many traits controlled by the ArlRS system, a major contributor to catheter colonization.
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Edited by: Andrea Guido Oreste Manetti, GlaxoSmithKline, United Kingdom
This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology
Reviewed by: Dipankar Ghosh, Jawaharlal Nehru University, India; Miguel A. De la Cruz, IMSS, Mexico; Meera Unnikrishnan, University of Warwick, United Kingdom
ISSN:1664-302X
1664-302X
DOI:10.3389/fmicb.2018.00342