title: Development of in vitro resistance to chitosan is related to changes in cell envelope structure of Staphylococcus aureus.
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.
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology Unit, University of Bonn, D-53115 Bonn, Germany. Electronic address: dina.raafat@uni-greifswald.de.
authors.forename: Dina
authors.initials: D
authors.lastname: Raafat
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology Unit, University of Bonn, D-53115 Bonn, Germany. Electronic address: Nicole.Leib1@gmx.de.
authors.forename: Nicole
authors.initials: N
authors.lastname: Leib
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology Unit, University of Bonn, D-53115 Bonn, Germany. Electronic address: mwilmes@uni-bonn.de.
authors.forename: Miriam
authors.initials: M
authors.lastname: Wilmes
authors.affiliation: Genomic Research Laboratory, Division of Infectious Diseases, University of Geneva Hospitals, CH-1211 Geneva, Switzerland. Electronic address: patrice.francois@genomic.ch.
authors.forename: Patrice
authors.initials: P
authors.lastname: François
authors.affiliation: Genomic Research Laboratory, Division of Infectious Diseases, University of Geneva Hospitals, CH-1211 Geneva, Switzerland. Electronic address: jacques.schrenzel@hcuge.ch.
authors.forename: Jacques
authors.initials: J
authors.lastname: Schrenzel
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology Unit, University of Bonn, D-53115 Bonn, Germany. Electronic address: hgsahl@uni-bonn.de.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Sahl
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000166:cytology* / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D048271:Chitosan
keywords: Antibiotic resistance; Chitosan; Microarray analysis; Phospholipids analysis