D-histidine combated biofilm formation and enhanced the effect of amikacin against Pseudomonas aeruginosa in vitro

Arch Microbiol. 2024 Mar 11;206(4):148. doi: 10.1007/s00203-024-03918-4.

Abstract

Pseudomonas aeruginosa is an opportunistic gram-negative pathogenic microorganism that poses a significant challenge in clinical treatment. Antibiotics exhibit limited efficacy against mature biofilm, culminating in an increase in the number of antibiotic-resistant strains. Therefore, novel strategies are essential to enhance the effectiveness of antibiotics against Pseudomonas aeruginosa biofilms. D-histidine has been previously identified as a prospective anti-biofilm agent. However, limited attention has been directed towards its impact on Pseudomonas aeruginosa. Therefore, this study was undertaken to explore the effect of D-histidine on Pseudomonas aeruginosa in vitro. Our results demonstrated that D-histidine downregulated the mRNA expression of virulence and quorum sensing (QS)-associated genes in Pseudomonas aeruginosa PAO1 without affecting bacterial growth. Swarming and swimming motility tests revealed that D-histidine significantly reduced the motility and pathogenicity of PAO1. Moreover, crystal violet staining and confocal laser scanning microscopy demonstrated that D-histidine inhibited biofilm formation and triggered the disassembly of mature biofilms. Notably, D-histidine increased the susceptibility of PAO1 to amikacin compared to that in the amikacin-alone group. These findings underscore the efficacy of D-histidine in combating Pseudomonas aeruginosa by reducing biofilm formation and increasing biofilm disassembly. Moreover, the combination of amikacin and D-histidine induced a synergistic effect against Pseudomonas aeruginosa biofilms, suggesting the potential utility of D-histidine as a preventive strategy against biofilm-associated infections caused by Pseudomonas aeruginosa.

Keywords: Pseudomonas aeruginosa; Biofilm; D-amino acid; D-histidine; Quorum sensing.

MeSH terms

  • Amikacin* / metabolism
  • Amikacin* / pharmacology
  • Amikacin* / therapeutic use
  • Anti-Bacterial Agents / chemistry
  • Biofilms
  • Histidine / metabolism
  • Histidine / pharmacology
  • Histidine / therapeutic use
  • Humans
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa
  • Quorum Sensing
  • Virulence Factors / metabolism

Substances

  • Amikacin
  • Histidine
  • Anti-Bacterial Agents
  • Virulence Factors