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Abstract <p>Gentamicin (Ge) plays a crucial role in treating infections caused by <i>Pseudomonas aeruginosa</i>. This study examined the effects of prolonged exposure of <i>P. aeruginosa</i> to sub-minimum inhibitory concentrations (sub-MIC) of Ge. <i>P. aeruginosa</i> ATCC 9027 (initial strain) was exposed to sub-MIC Ge for 14 days (Ge-E1), then subsequently cultured in an antibiotic-free environment for 10 days (Ge-E2). Comparative analyses on antibiotic susceptibility profiles, morphology, key virulence features, proteome and noted target gene expression of the initial strain, Ge-E1 and Ge-E2 were performed. Resultedly, the initial strain shifted from being susceptible to Ge with an MIC of 2 μg/mL to resistant in Ge-E1 and Ge-E2 with an MIC of 256 and 128&#xa0;μg/mL, respectively. Cross-resistance to multiple antibiotic classes was observed. Morphologically, Ge‑E1 exhibited a marked reduction in cell size, whereas Ge-E2 largely returned to its initial size. Regarding virulence, Ge exposure markedly suppressed rhamnolipid secretion, pyocyanin and pyoverdine production. Swarming motility was notably reduced in Ge-E1 and not fully reverted in Ge-E2. Proteomic analysis identified 994 proteins, of which approximately 47% were differentially expressed proteins (DEPs). A predominance of down-regulated proteins, primarily proteins related to ribosome function, cellular and metabolic processes, was found in both Ge-E1 and Ge-E2. Particularly, noted proteomic changes included the upregulation of <i>mvaT</i>, a global transcriptional regulator, and the down-regulation of <i>rpoB</i> and <i>rpsL</i>, involved in transcription and ribosomal function, respectively, as well as <i>oprD</i>, a porin protein linked to membrane transport. Furthermore, RT-qPCR results confirmed the proteomic data and further revealed downregulation of <i>rpoB</i>, <i>sdhA</i>, <i>phzM</i>, and <i>rpsL</i>, while <i>mvaT</i> and <i>rmpA</i> were consistently upregulated in both Ge-E1 and Ge-E2. In conclusion, prolonged exposure to sub-MIC levels of Ge induced stable resistance, relatively reversible phenotypic alterations, and coordinated transcriptional and proteomic responses in <i>P. aeruginosa</i>.</p>

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Phenotypic and Proteomic Alterations in Pseudomonas aeruginosa ATCC 9027 Induced by Prolonged Sub-MIC Gentamicin Exposure

  • 期刊论文

  • 发表日期：

    2026年3月2日

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  • T. K. O. Huynh,
  • T. Q. Huynh,
  • N. B. V. Tran,
  • T. T. Thieu,
  • T. T. V. Pham,
  • T. P. Truong,
  • V. A. Huynh,
  • T. T. L. Trinh,
  • T. H. Nguyen,
  • Q. Lin,
  • T. K. Lim,
  • Q. Lin,
  • T. T. H. Nguyen

摘要

Abstract

Gentamicin (Ge) plays a crucial role in treating infections caused by Pseudomonas aeruginosa. This study examined the effects of prolonged exposure of P. aeruginosa to sub-minimum inhibitory concentrations (sub-MIC) of Ge. P. aeruginosa ATCC 9027 (initial strain) was exposed to sub-MIC Ge for 14 days (Ge-E1), then subsequently cultured in an antibiotic-free environment for 10 days (Ge-E2). Comparative analyses on antibiotic susceptibility profiles, morphology, key virulence features, proteome and noted target gene expression of the initial strain, Ge-E1 and Ge-E2 were performed. Resultedly, the initial strain shifted from being susceptible to Ge with an MIC of 2 μg/mL to resistant in Ge-E1 and Ge-E2 with an MIC of 256 and 128 μg/mL, respectively. Cross-resistance to multiple antibiotic classes was observed. Morphologically, Ge‑E1 exhibited a marked reduction in cell size, whereas Ge-E2 largely returned to its initial size. Regarding virulence, Ge exposure markedly suppressed rhamnolipid secretion, pyocyanin and pyoverdine production. Swarming motility was notably reduced in Ge-E1 and not fully reverted in Ge-E2. Proteomic analysis identified 994 proteins, of which approximately 47% were differentially expressed proteins (DEPs). A predominance of down-regulated proteins, primarily proteins related to ribosome function, cellular and metabolic processes, was found in both Ge-E1 and Ge-E2. Particularly, noted proteomic changes included the upregulation of mvaT, a global transcriptional regulator, and the down-regulation of rpoB and rpsL, involved in transcription and ribosomal function, respectively, as well as oprD, a porin protein linked to membrane transport. Furthermore, RT-qPCR results confirmed the proteomic data and further revealed downregulation of rpoB, sdhA, phzM, and rpsL, while mvaT and rmpA were consistently upregulated in both Ge-E1 and Ge-E2. In conclusion, prolonged exposure to sub-MIC levels of Ge induced stable resistance, relatively reversible phenotypic alterations, and coordinated transcriptional and proteomic responses in P. aeruginosa.