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Background <p>Multidrug-resistant (MDR), and mucoid <i>Pseudomonas aeruginosa</i> strains are relatively uncommon in clinical settings, and genomic data concerning such strains are particularly scarce, which limits the comprehensive understanding of this group of opportunistic pathogens. This study systematically characterized two clinically isolated, carbapenem-resistant, MDR, and highly mucoid <i>P. aeruginosa</i> strains, designated YL-1 and YL-2. We employed whole-genome sequencing, comparative genomics, and quantitative PCR (qPCR) to investigate the mechanisms of multidrug resistance and other phenotypic variations. Their pathogenicity was further compared using a <i>Galleria mellonella</i> infection model.</p> Results <p>Neither YL-1 nor YL-2 harbors plasmids; all resistance and virulence associated genes were located on their chromosomes. Only 9 genomic sites differ between the two strains, suggesting they derived from a common ancestor but have diverged evolutionarily. In the phylogenetic tree, both strains were located in the evolutionary branch containing the hypervirulent reference strain PA14. Mutations in <i>oprD</i> and AmpC regulatory element, and overexpressed efflux pumps contributed to their multidrug resistance, particularly to carbapenems. In YL-2, a frameshift mutation inactivated <i>gacS</i>, a key virulence regulator, which likely accounts for its significantly lower pyocyanin production compared to YL-1. The mortality rate of <i>G. mellonella</i> larvae infected with YL-1 was significantly higher than that of YL-2, indicating that YL-1 is more virulent.</p> Conclusion <p>This study provides a comprehensive genomic and phenotypic analysis of two MDR hypermucoid <i>P. aeruginosa</i> strains, shedding light on their in vivo microevolution. These findings offer the theory for the clinical management and control of hypermucoid <i>P. aeruginosa</i> infections.</p>

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Parallel microevolution of multidrug resistance and hypermucoviscosity in two carbapenem-resistant Pseudomonas aeruginosa clinical isolates with strikingly divergent virulence outcomes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月27日

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  • Rui Yang,
  • Ruolin Zhu,
  • Chunmiao Lai,
  • Jie Zeng,
  • Anran Zheng,
  • Pinjia Chen,
  • Xiaoying Chen,
  • Xiaoxin Tian,
  • Xin Wang,
  • Shengjun Feng,
  • Na Mi,
  • Xinyun Liang,
  • Min Chen,
  • Wei Zhang,
  • Qiujia Wen,
  • Min Zhang,
  • Xiaomei Tang,
  • Yinqiang Fan,
  • Heping Wang,
  • Tingting Zhi,
  • Zuguo Zhao

摘要

Background

Multidrug-resistant (MDR), and mucoid Pseudomonas aeruginosa strains are relatively uncommon in clinical settings, and genomic data concerning such strains are particularly scarce, which limits the comprehensive understanding of this group of opportunistic pathogens. This study systematically characterized two clinically isolated, carbapenem-resistant, MDR, and highly mucoid P. aeruginosa strains, designated YL-1 and YL-2. We employed whole-genome sequencing, comparative genomics, and quantitative PCR (qPCR) to investigate the mechanisms of multidrug resistance and other phenotypic variations. Their pathogenicity was further compared using a Galleria mellonella infection model.

Results

Neither YL-1 nor YL-2 harbors plasmids; all resistance and virulence associated genes were located on their chromosomes. Only 9 genomic sites differ between the two strains, suggesting they derived from a common ancestor but have diverged evolutionarily. In the phylogenetic tree, both strains were located in the evolutionary branch containing the hypervirulent reference strain PA14. Mutations in oprD and AmpC regulatory element, and overexpressed efflux pumps contributed to their multidrug resistance, particularly to carbapenems. In YL-2, a frameshift mutation inactivated gacS, a key virulence regulator, which likely accounts for its significantly lower pyocyanin production compared to YL-1. The mortality rate of G. mellonella larvae infected with YL-1 was significantly higher than that of YL-2, indicating that YL-1 is more virulent.

Conclusion

This study provides a comprehensive genomic and phenotypic analysis of two MDR hypermucoid P. aeruginosa strains, shedding light on their in vivo microevolution. These findings offer the theory for the clinical management and control of hypermucoid P. aeruginosa infections.