Development of in vitro resistance to chitosan is related to changes in cell envelope structure of Staphylococcus aureus. (10th February 2017)

• Record Type: Journal Article
• Authors: Raafat, Dina; Leib, Nicole; Wilmes, Miriam; François, Patrice; Schrenzel, Jacques; Sahl, Hans-Georg
• Is Part Of: Carbohydrate polymers. Volume 157(2017)
• Page Start: 146
• Page End: 155
• Publication Date: 2017-02-10
• Subjects: AMP antimicrobial peptide -- CAMHB cation-adjusted Mueller–Hinton II broth -- CL cardiolipin -- CRV chitosan-resistant variant -- FDR False Discovery Rate -- HMG-CoA Hydroxymethylglutaryl-CoA -- L-PG lysyl-phosphotidylglycerol -- MBC minimum bactericidal concentration -- MIC minimum inhibitory concentration -- OD optical density -- ORF Open Reading Frame -- PG phosphatidylglycerol -- PL phospholipid -- RT room temperature -- TCRS two-component regulatory system -- TEM Transmission electron microscope -- WT wild-type; Chitosan -- Antibiotic resistance -- Phospholipids analysis -- Microarray analysis; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2016.09.075
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: A stable chitosan-resistant variant (CRV) of S. aureus SG511-Berlin was selected. Changes in bacterial envelope are related to the observed resistance to chitosan. Increased positive bacterial surface charge resulted in reduced chitosan binding. Higher membrane levels of LPG increase electrostatic repulsion of chitosan. The CRV has a repaired sensor histidine kinase GraS. Abstract: The bacterial cell envelope is believed to be a principal target for initiating the staphylocidal pathway of chitosan. The present study was therefore designed to investigate possible changes in cell surface phenotypes related to the in vitro chitosan resistance development in the laboratory strain S. aureus SG511-Berlin. Following a serial passage experiment, a stable chitosan-resistant variant (CRV) was identified, exhibiting >50-fold reduction in its sensitivity towards chitosan. Our analyses of the CRV identified phenotypic and genotypic features that readily distinguished it from its chitosan-susceptible parental strain, including: (i) a lower overall negative cell surface charge; (ii) cross-resistance to a number of antimicrobial agents; (iii) major alterations in cell envelope structure, cellular bioenergetics and metabolism (based on transcriptional profiling); and (iv) a repaired sensor histidine kinase GraS. Our data therefore suggest a close nexus between changes in cell envelope properties with the in vitro chitosan-resistant phenotype in S. aureus SG511-Berlin.