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<p>The emergence of antimicrobial drug-resistant pathogens poses a significant threat to human health, amidst the escalating risk of infectious diseases. BamA, a critical protein in bacterial outer membrane assembly and toxicity regulation, has emerged as a promising target for novel antimicrobial strategies. In this study, we designed two antimicrobial peptides (AMPs), namely LR-11 and DR-11, by targeting the BamA protein. The experimental results demonstrate that both LR-11 and DR-11 exhibit potent antibacterial activity across a broad spectrum of bacterial strains. LR-11 and DR-11 both exhibit a MIC of 4&#xa0;µg/mL against <i>Staphylococcus aureus</i>. Notably, DR-11 also exhibited an MIC of 4&#xa0;µg/mL against <i>Pseudomonas aeruginosa</i>, <i>Enterococcus faecalis</i>, and <i>carbapenem-resistant Pseudomonas aeruginosa</i>. Although both peptides demonstrated comparable antibacterial activity against Staphylococcus aureus, DR-11 displayed a broader antimicrobial spectrum against the aforementioned test strains. The inhibition rates of LR-11 and DR-11 against bacterial biofilms were 92.25% and 90.45%, respectively, highlighting their efficacy in combating bacterial biofilms. Surface plasmon resonance (SPR) analysis revealed binding affinity (K<sub>D</sub> value) between BamA and LR-11 and DR-11 was 5.428E<sup>−5</sup>M and 1.767E<sup>−5</sup>M, respectively, reaching micromolar levels. In silkworm disease models, LR-11 and DR-11 exhibited significant antibacterial activity against pathogenic Enterococcus species, markedly prolonging the survival of infected individuals. In a murine model of diabetic wound infection, DR-11 significantly accelerated wound healing through its antimicrobial action. Collectively, these findings demonstrate that LR-11 and DR-11 are broad-spectrum AMPs capable of inhibiting both susceptible and drug-resistant bacterial strains, highlighting their potential for wide-ranging applications in clinical medicine and agriculture.</p>

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Design of AMPs Targeting BamA as a Potential Target and Research on Their Antimicrobial Mechanisms

  • 期刊论文

  • 发表日期：

    2026年3月31日

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  • Hongyou Chen,
  • Xu Zou,
  • Peiqi Peng,
  • Mingtao Peng,
  • Haoran Liang,
  • Minghe Luo,
  • Tao Wang,
  • Ning Zhang,
  • Qing Zhang,
  • Yuanqiang Wang

摘要

The emergence of antimicrobial drug-resistant pathogens poses a significant threat to human health, amidst the escalating risk of infectious diseases. BamA, a critical protein in bacterial outer membrane assembly and toxicity regulation, has emerged as a promising target for novel antimicrobial strategies. In this study, we designed two antimicrobial peptides (AMPs), namely LR-11 and DR-11, by targeting the BamA protein. The experimental results demonstrate that both LR-11 and DR-11 exhibit potent antibacterial activity across a broad spectrum of bacterial strains. LR-11 and DR-11 both exhibit a MIC of 4 µg/mL against Staphylococcus aureus. Notably, DR-11 also exhibited an MIC of 4 µg/mL against Pseudomonas aeruginosa, Enterococcus faecalis, and carbapenem-resistant Pseudomonas aeruginosa. Although both peptides demonstrated comparable antibacterial activity against Staphylococcus aureus, DR-11 displayed a broader antimicrobial spectrum against the aforementioned test strains. The inhibition rates of LR-11 and DR-11 against bacterial biofilms were 92.25% and 90.45%, respectively, highlighting their efficacy in combating bacterial biofilms. Surface plasmon resonance (SPR) analysis revealed binding affinity (KD value) between BamA and LR-11 and DR-11 was 5.428E−5M and 1.767E−5M, respectively, reaching micromolar levels. In silkworm disease models, LR-11 and DR-11 exhibited significant antibacterial activity against pathogenic Enterococcus species, markedly prolonging the survival of infected individuals. In a murine model of diabetic wound infection, DR-11 significantly accelerated wound healing through its antimicrobial action. Collectively, these findings demonstrate that LR-11 and DR-11 are broad-spectrum AMPs capable of inhibiting both susceptible and drug-resistant bacterial strains, highlighting their potential for wide-ranging applications in clinical medicine and agriculture.