The clinical significance of silent mutations with respect to ciprofloxacin resistance in MRSA

Abstract

Background: The aim of this study was to investigate the genotypic differences between different sequence type MRSA isolates, especially focusing on silent rpoB474 mutations and the relationship between such mutations and ciprofloxacin resistance.

Methods: Seventy-nine MRSA isolates were obtained for antibiotic susceptibility tests and molecular study.

Results: Among these isolates, we found that the MIC₅₀, MIC₉₀, and minimum inhibitory concentration (MIC) range of ciprofloxacin were much higher for the isolates without the rpoB474 mutation than for isolates with the rpoB474 mutation. A total of 87.5% of the isolates with the rpoB474 mutation were susceptible to ciprofloxacin, but none of the isolates without the rpoB474 mutation were susceptible to ciprofloxacin. For 27 MRSA isolates without rpo474 silent mutation but with gyrA86/126 silent mutation, all of them belonged to SCCmec III, and had high ciprofloxacin MIC levels. For another 44 MRSA isolates with rpo474 silent mutation but without gyrA86/126 silent mutation, all of them showed low ciprofloxacin MIC levels, all of them belonged to either SCCmec IV or V. Furthermore, MRSA ciprofloxacin resistance was found to be associated with the mutations gyrA S84L/parC S80F or gyrA S84L, and S85P/parC S80Y.

Conclusion: Most occurrences of this rpoB474 silent mutation were found in community acquired-MRSA (CA-MRSA) isolates with susceptibility to most antibiotics, especially for ciprofloxacin and vice versa. Thus, this mutation may help to differentiate the different microbiologic characteristics of MRSA clinical isolates.

Keywords: MRSA; ciprofloxacin; resistance; rpoB474; silent mutation.

Figure 1

PFGE and molecular patterns of MRSA isolates. Abbreviations: PFGE, pulsed-field gel electrophoresis; MRSA, methicillin-resistant Staphylococcus aureus; opt, optimization; tol, tolerance; PVL, Panton–Valentine leucocidin; ST, sequence type; TIST, Tigecycline In-vitro Surveillance in Taiwan.