Scholarlink

Background <p>Carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) has emerged as a critical threat in bloodstream infections (BSIs), with rising global prevalence and elevated mortality rates. Traditional surveillance methods often lacks resolution for resistance-virulence-transmission interplay, highlighting the importance of high-resolution genomics. Whole-genome sequencing (WGS) has enabled unprecedented resolution in dissecting CRPA’s genetic landscape, revealing links between resistance, virulence, and outcomes.</p> Results <p>This study employed WGS to characterize 61 <i>P. aeruginosa</i> isolates from BSIs, with a focus on 18 CRPA strains. Clinical data linked central venous catheterization to CRPA BSI development (OR = 6.6, <i>p</i> = 0.002) and identified carbapenem exposure, mechanical ventilation, and low hemoglobin as independent mortality risk factors. WGS identified 33.3% (<i>n</i> = 6, 6/18) of the strains harbored β-lactamase genes, and 44.4%(<i>n</i> = 8, 8/18) of the strains carried truncated OprD protein due to frameshift mutations or point mutations inducing translational truncation. Efflux pump overexpression (61.1% with ≥ 2-fold upregulation) further contributed to this resistance phenotype. MLST identified 49 distinct STs (including 2 novel types) and a pattern of endemic diversification. O11 is strongly linked to carbapenem resistance (CRPA: <i>p</i> = 0.02; MDRPA: <i>p</i> = 0.004), correlating with <i>oprD</i> mutations (<i>p</i> = 0.008) and <i>exoU</i>+/<i>exoS</i>-, indicating enhanced nosocomial adaptability.</p> Conclusions <p>A very high genetic diversity was noted amongst <i>P. aeruginosa</i> strains isolated from BSIs cases. The mechanism of carbapenem resistance is mainly attributed to <i>oprD</i> mutations and efflux pumps activation, with carbapenemases emerging as an additional mechanism of concern. These resistance mechanisms with high-risk clinical factors collectively indicate that strict policies are essential for in CRPA BSIs management.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Whole-genome sequencing reveals resistance mechanisms and molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa bloodstream infections

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月22日

查看全文
  • Yongqin Guo,
  • Yangyang Hao,
  • Mingchen Huang,
  • Yihua Sun,
  • Zhibo Tao,
  • Yang Liu,
  • Shanshan Huang,
  • Peng Liu,
  • Dandan Wei

摘要

Background

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has emerged as a critical threat in bloodstream infections (BSIs), with rising global prevalence and elevated mortality rates. Traditional surveillance methods often lacks resolution for resistance-virulence-transmission interplay, highlighting the importance of high-resolution genomics. Whole-genome sequencing (WGS) has enabled unprecedented resolution in dissecting CRPA’s genetic landscape, revealing links between resistance, virulence, and outcomes.

Results

This study employed WGS to characterize 61 P. aeruginosa isolates from BSIs, with a focus on 18 CRPA strains. Clinical data linked central venous catheterization to CRPA BSI development (OR = 6.6, p = 0.002) and identified carbapenem exposure, mechanical ventilation, and low hemoglobin as independent mortality risk factors. WGS identified 33.3% (n = 6, 6/18) of the strains harbored β-lactamase genes, and 44.4%(n = 8, 8/18) of the strains carried truncated OprD protein due to frameshift mutations or point mutations inducing translational truncation. Efflux pump overexpression (61.1% with ≥ 2-fold upregulation) further contributed to this resistance phenotype. MLST identified 49 distinct STs (including 2 novel types) and a pattern of endemic diversification. O11 is strongly linked to carbapenem resistance (CRPA: p = 0.02; MDRPA: p = 0.004), correlating with oprD mutations (p = 0.008) and exoU+/exoS-, indicating enhanced nosocomial adaptability.

Conclusions

A very high genetic diversity was noted amongst P. aeruginosa strains isolated from BSIs cases. The mechanism of carbapenem resistance is mainly attributed to oprD mutations and efflux pumps activation, with carbapenemases emerging as an additional mechanism of concern. These resistance mechanisms with high-risk clinical factors collectively indicate that strict policies are essential for in CRPA BSIs management.