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Abstract <p><i>Pseudomonas aeruginosa</i> constitutes a substantial health risk, instigating diseases such as pneumonia and sepsis in vulnerable hospitalized patients. The World Health Organization categorizes it as a high-priority bacterial pathogen owing to its marked resistance to multiple antibiotics. This pathogen poses substantial management challenges, thereby necessitating the exploration of alternative therapeutic strategies. Computational methodologies facilitate the rapid identification of antimicrobial peptides (AMPs) with heightened specificity and effectiveness against <i>P. aeruginosa</i> by employing genomic, transcriptomic, and structural data. This <i>in silico</i> study aims to identify AMPs from <i>Bacillus</i> and <i>Pseudomonas</i> genomes that may act against multidrug-resistant (MDR) <i>P. aeruginosa</i> by targeting Pyocyanin (PYC, a pigment virulence factor) and key membrane lipids. From 500 AMPs analyzed in the 351 genomes of <i>Bacillus</i> and <i>Pseudomonas</i>, three noteworthy candidates were identified: UviB from <i>Bacillus altitudinis</i>, along with two Colicins from <i>P. koreensis</i> and <i>P. monsensis</i>. The Colicins surpassed UviB in all evaluations, being nontoxic, nonhemolytic, nonallergic, biofilm-active, highly stable, and immunogenic, thus encouraging further investigation. The Colicin from <i>P. koreensis</i> (Colicin<i>Pk</i>) exhibited significant non-bonded interactions with PYC, maintaining persistent proximity throughout the simulations. Both Colicin<i>Pk</i> and Colicin<i>Pm</i> (from <i>P. monsensis</i>) encompassed the pathogen’s primary lipids, Phosphatidylglycerol (PGL) and Phosphatidylethanolamine (PEA), respectively. The separation of Colicin<i>Pk</i> from PGL was dynamically constrained via transient hydrogen bonds and non-bonded interactions. Colicin<i>Pm</i>-PEA also showed an attractive free energy landscape like Colicin<i>Pk</i>-PYC. Hence, these Colicins might counteract MDR <i>P. aeruginosa</i> by neutralizing PYC and damaging its membrane structure through interactions with key lipid backbones.</p> Graphic Abstract <p></p>

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Mining Microbial Genomes for Anti-Pseudomonal Peptides: A Translational In Silico Framework

  • 期刊论文

  • 发表日期：

    2026年3月3日

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  • Rajendra Kr Roy,
  • Raju Biswas,
  • Anubhab Laha,
  • Rajdeep Shaw,
  • Rahul Chandra,
  • Anindya Sundar Panja,
  • Analabha Roy,
  • Rajib Bandopadhyay

摘要

Abstract

Pseudomonas aeruginosa constitutes a substantial health risk, instigating diseases such as pneumonia and sepsis in vulnerable hospitalized patients. The World Health Organization categorizes it as a high-priority bacterial pathogen owing to its marked resistance to multiple antibiotics. This pathogen poses substantial management challenges, thereby necessitating the exploration of alternative therapeutic strategies. Computational methodologies facilitate the rapid identification of antimicrobial peptides (AMPs) with heightened specificity and effectiveness against P. aeruginosa by employing genomic, transcriptomic, and structural data. This in silico study aims to identify AMPs from Bacillus and Pseudomonas genomes that may act against multidrug-resistant (MDR) P. aeruginosa by targeting Pyocyanin (PYC, a pigment virulence factor) and key membrane lipids. From 500 AMPs analyzed in the 351 genomes of Bacillus and Pseudomonas, three noteworthy candidates were identified: UviB from Bacillus altitudinis, along with two Colicins from P. koreensis and P. monsensis. The Colicins surpassed UviB in all evaluations, being nontoxic, nonhemolytic, nonallergic, biofilm-active, highly stable, and immunogenic, thus encouraging further investigation. The Colicin from P. koreensis (ColicinPk) exhibited significant non-bonded interactions with PYC, maintaining persistent proximity throughout the simulations. Both ColicinPk and ColicinPm (from P. monsensis) encompassed the pathogen’s primary lipids, Phosphatidylglycerol (PGL) and Phosphatidylethanolamine (PEA), respectively. The separation of ColicinPk from PGL was dynamically constrained via transient hydrogen bonds and non-bonded interactions. ColicinPm-PEA also showed an attractive free energy landscape like ColicinPk-PYC. Hence, these Colicins might counteract MDR P. aeruginosa by neutralizing PYC and damaging its membrane structure through interactions with key lipid backbones.

Graphic Abstract