Mechanisms of linezolid-resistant Staphylococcus capitis with the novel mutation C2128T in the 23S rRNA in China

Abstract Purpose: Linezolid is the first oral oxazolidinone antibiotic approved for clinical application. With the widespread use of the linezolid, there are increasing reports of the linezolid-resistant (LZR). The objective of this study was to investigate the molecular characteristics and the potential resistance mechanisms of the LZR Staphylococcus capitis isolates from a tertiary hospital in China.Methods: The agar dilution and E-test methods were used to detect antibiotic resistance. The carrying status of the chloramphenicol-florfenicol resistance (cfr) gene in the strains was detected by PCR. Whole-genome sequencing (WGS) was used to detect point mutations, L3, L4, and L22 mutations, and also to study the genetic environment of the cfr gene and the relationship between strains. Results: A similar pattern in susceptibility profiles were observed in all four S. capitis strains, each exhibiting a multidrug-resistant phenotype. A potential novel mutation, C2128T, was identified, and the cfr genes of S. capitis strains were all positive. Additionally, the same mutation (C2128T and G2600T) was identified in all 23S rRNA sequences of isolates, while the mutation was lacking in the L3, L4, and L22 ribosomal proteins. The genetic environments surrounding cfr were identical in all four isolates. A schematic diagram of the phylogenetic tree exhibited that they were closely related to AYP1020, CR01, and TW2795, and a total of seven drug-resistant genes were detected in these strains. Conclusions: The study indicated that the resistance of the Staphylococcus capitis strains to linezolid was caused by multiple mechanisms and a potential novel mutation C2128T was identified which may have an impact on bacterial resistance.