Molecular Epidemiology and Mechanisms of 43 Low-Level Linezolid-Resistant Strains in Chongqing, China.

BACKGROUND

strains with low-level resistance to linezolid (an oxazolidinone antibiotic) have become common. No large-scale study has examined the underlying mechanisms in linezolid-resistant (LRE) strains. We investigated these mechanisms and molecular characteristics in Chongqing, China.

METHODS

A total of 1,120 non-duplicated strains collected from August 2014 to June 2017 underwent drug susceptibility testing. LRE strains were screened for , , and mutations in the 23S rRNA and ribosomal proteins L3 and L4 by PCR amplification and sequencing. Multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were used for epidemiological analysis.

RESULTS

All 43 low-level LRE strains (minimum inhibitory concentration: 8-16 mg/L) harbored ; and 23S rRNA mutations were not detected. Novel mutations in the ribosomal proteins L3 and L4-one deletion (Q103del) and four substitutions (S113L, T35A, I98V, and N79D)-were identified. Novel amino acid substitutions at positions E60K, G197D, and T285P of the OptrA protein were observed. MLST revealed 20 types of LRE strains; the most common type was ST16 (32.6%). PFGE showed 14 strains of ST16 with unique banding patterns. Eight novel sequence types (ST823 to ST830) and one allele (95) were identified for the first time in China.

CONCLUSIONS

plays an important role in linezolid resistance and may serve as a marker for resistance screening. Since the L3 and L4 mutations did not simultaneously occur in the same strain, they play a negligible role in linezolid resistance. Epidemiological investigation suggested that the LRE cases were sporadic.