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Published on: February 10, 2011
Molecular Characterization of Linezolid-Non-Susceptible Enterococcus faecium: Identification of optrA and vanM
Hong Shen1, Xi Chen1, Jun Liu1
1Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.
Purpose:
This study aimed to explore the resistance mechanisms and molecular characteristics of linezolid-non-susceptible Enterococcus faecium isolates (LNSEFM) from a tertiary hospital in Beijing, China, focusing on novel findings with significant clinical and epidemiological implications.
Patients And Methods:
LNSEFM strains isolated from clinical specimens between January 2011 and December 2023 were collected and screened for resistance genes, including rplC, rplD, rplV, 23s rRNA, optrA, poxtA, and cfr using polymerase chain reaction (PCR) and DNA sequencing. Molecular epidemiological analysis was performed using multi-locus sequence typing (MLST). Isolates carrying optrA and those harboring poxtA were subjected to whole-genome sequencing (WGS).
Results:
Among 2384 clinical E. faecium isolates, 19 (0.80%) were linezolid-non-susceptible (MIC 4-32 mg/L). Among these, two vancomycin-resistant Enterococcus (VRE) strains exhibited an intermediate susceptibility to linezolid. Two distinct optrA variants (designated as KLDK and KLDP) were detected in separate LNSEFM isolates. The KLDK-positive isolate was found to co-harbor the vanM gene cluster despite maintaining vancomycin susceptibility. Additionally, one linezolid-resistant isolate carried a G2576T mutation in the 23S rRNA gene, whereas the other harbored the poxtA gene. MLST revealed 13 sequence types (STs) among the isolates, including a novel type ST2709.
Conclusion:
This study identified key notable findings in LNSEFM: identification of linezolid intermediate VRE in China, clinical detection of the optrA KLDK variant in enterococci, optrA-vanM co-presence in vancomycin-susceptible E. faecium, and a novel sequence type (ST2709). These findings enrich our understanding of the molecular epidemiology of LNSEFM and provide critical insights into clinical antimicrobial management and infection control.
Insights
This study identified linezolid-non-susceptible Enterococcus faecium in China, including novel resistance mechanisms and a new sequence type. These findings are crucial for understanding and managing antimicrobial resistance in clinical settings.
Area of Science:
- Microbiology
- Molecular Biology
- Epidemiology
Background:
- Linezolid is a critical antibiotic for treating infections caused by Gram-positive bacteria.
- Emergence of linezolid resistance in Enterococcus faecium poses a significant threat to public health.
- Understanding resistance mechanisms is vital for effective antimicrobial stewardship.
Purpose of the Study:
- To investigate the resistance mechanisms and molecular characteristics of linezolid-non-susceptible Enterococcus faecium (LNSEFM) isolates.
- To identify novel genetic elements and epidemiological features associated with linezolid resistance in China.
- To provide insights into clinical and epidemiological implications of LNSEFM.
Main Methods:
- Screening of LNSEFM isolates for resistance genes (e.g., optrA, poxtA, cfr, 23S rRNA mutations) using PCR and DNA sequencing.
- Molecular typing using Multi-Locus Sequence Typing (MLST).
- Whole-genome sequencing (WGS) for isolates with optrA and poxtA genes.
Main Results:
- 19 (0.80%) of 2384 E. faecium isolates were non-susceptible to linezolid.
- Two vancomycin-resistant Enterococcus (VRE) strains showed intermediate susceptibility to linezolid.
- Novel optrA variants (KLDK, KLDP) were detected; KLDK co-existed with vanM in a vancomycin-susceptible isolate.
- A novel ST2709 was identified among the LNSEFM isolates.
Conclusions:
- First identification of linezolid-intermediate VRE in China.
- Clinical detection of the optrA KLDK variant and optrA-vanM co-presence in vancomycin-susceptible E. faecium.
- Discovery of a novel ST2709 enhances understanding of LNSEFM molecular epidemiology.
- Findings offer critical insights for antimicrobial management and infection control strategies.
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