Development of in vitro resistance to chitosan is related to changes in cell envelope structure of Staphylococcus aureus

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.