Correlation between the antibiotic resistance and virulence determinants of vancomycin-resistant enterococci: paradoxical involvement of vanA in phenotypic resistance to teicoplanin

万古霉素耐药肠球菌的抗生素耐药性和毒力决定因素之间的相关性:vanA 基因在替考拉宁表型耐药性中的悖论性作用

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Abstract

BACKGROUND: Antimicrobial resistance, particularly in clinical Enterococcus isolates, poses a serious global health threat because of difficult-to-treat nosocomial infections. The emergence of vancomycin-resistant enterococci (VRE), mediated by VanA or VanB operons, has significantly limited treatment options. This study aimed at identifying antibiotic resistance and virulence genes in enterococci and exploring potential correlations between these genetic traits. METHODS: A total of 100 suspected enterococci were gathered from two hospitals and identified through phenotypic methods and the VITEK 2 Compact system. The Kirby-Bauer disk diffusion and MIC by microbroth dilution methods were employed for antimicrobial susceptibility. The gelatinase production and biofilm were evaluated phenotypically, while the presence of vancomycin resistance (vanA, vanB) and virulence (esp, gelE, hyl) genes was confirmed by PCR and sequenced for genetic characterization. RESULTS: Sixty-five Enterococcus isolates were characterized, with E. faecium (50.7%) and E. faecalis (41.5%) being the predominant species. Linezolid, teicoplanin, and chloramphenicol still retain good activity with 6.15%, 10.7%, and 29.2% resistance, respectively. About 40% of isolates were VRE, and all harbored the vanA gene. Biofilm formation and gelatinase production were most prevalent in E. faecium and E. faecalis, indicating enhanced virulence. Sequencing confirmed the chromosomal location and identity of the resistance and virulence genes, supporting their accurate detection and distribution among different Enterococcus species. Statistical analysis revealed that both esp and gelE genes were significantly associated with biofilm formation and gelatinase activity; however, esp showed a positive correlation with vanA and vancomycin resistance, while gelE demonstrated a negative correlation. Even though vanA is typically linked to high levels of resistance to both teicoplanin and vancomycin, only seven out of the twenty-six isolates that were vanA-positive showed phenotypic resistance to teicoplanin. CONCLUSION: Enterococcus faecium and E. faecalis were identified as predominant multidrug-resistant species carrying multiple virulence determinants, with esp and gelE strongly linked to biofilm formation and gelatinase activity. Linezolid, teicoplanin, and chloramphenicol remained the most effective agents. Our findings demonstrate the coexistence of resistance and virulence traits, along with unexpected genotype-phenotype variations, underscoring the need for integrated molecular and phenotypic approaches in surveillance and clinical management.

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