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Outer membrane protein I of Pseudomonas aeruginosa is a target of cationic antimicrobial peptide/protein

Yu-Min Lin1, Shih-Jung Wu, Ting-Wei Chang

  • 1Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.

The Journal of Biological Chemistry
|January 27, 2010
PubMed

Insights

Pseudomonas aeruginosa outer membrane protein I (OprI) mediates susceptibility to human ribonuclease 7 (hRNase 7) and other cationic antimicrobial peptides (AMPs). This discovery reveals a new target for developing drugs against antibiotic-resistant bacteria.

Area of Science:

  • Microbiology and Immunology
  • Bacterial Pathogenesis
  • Antimicrobial Drug Discovery

Background:

  • Cationic antimicrobial peptides/proteins (AMPs) are crucial for innate immunity against microbial infections.
  • Pseudomonas aeruginosa is a significant opportunistic pathogen, often exhibiting antibiotic resistance.
  • Lipopolysaccharide (LPS) is typically considered the primary binding site for cationic AMPs on Gram-negative bacteria.

Purpose of the Study:

  • To identify the specific target of human ribonuclease 7 (hRNase 7) and alpha-helical cationic AMPs on Pseudomonas aeruginosa.
  • To elucidate the mechanism by which OprI influences bacterial susceptibility to these antimicrobial agents.
  • To explore OprI as a potential therapeutic target for combating antibiotic-resistant infections.

Main Methods:

  • Investigated the role of outer membrane protein I (OprI) in P. aeruginosa susceptibility to hRNase 7 and alpha-helical cationic AMPs.
  • Assessed the inhibitory effects of exogenous OprI and anti-OprI antibodies on antimicrobial activity.
  • Analyzed the consequences of OprI modification and internalization by hRNase 7 on bacterial membrane permeability and metabolite leakage.
  • Predicted the structural features of OprI involved in binding and anchoring.

Main Results:

  • Outer membrane protein I (OprI), not lipopolysaccharide, was identified as the key factor determining P. aeruginosa susceptibility to hRNase 7 and alpha-helical cationic AMPs.
  • Antimicrobial activity was significantly inhibited by the presence of OprI or antibodies targeting OprI.
  • hRNase 7-mediated modification and internalization of OprI led to increased bacterial membrane permeability and metabolite release.
  • OprI possesses structural elements, including an N-terminal loop and a C-terminal lysine, facilitating binding and anchoring.

Conclusions:

  • OprI represents a novel target for alpha-helical cationic AMPs, offering a new mechanism of antimicrobial action against P. aeruginosa.
  • Targeting OprI could be a viable strategy for developing new therapeutics against antibiotic-resistant bacterial infections.
  • These findings challenge the traditional view of LPS as the sole initial binding site for cationic AMPs.

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