Increased resistance to cationic antimicrobial peptide LL-37 in methicillin-resistant strains of Staphylococcus

Kazuhisa Ouhara1, Hitoshi Komatsuzawa, Toshihisa Kawai

  • 1Department of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.

Abstract

Insights

Methicillin-resistant Staphylococcus aureus (MRSA) with higher net charge shows increased resistance to the antimicrobial peptide LL-37, but not human beta-defensin-3 (hBD3). This finding is crucial for understanding MRSA infections and developing new treatments.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Biochemistry

Background:

  • Staphylococcus aureus, including methicillin-resistant strains (MRSA), poses a significant threat due to antimicrobial resistance.
  • Host-derived cationic antimicrobial peptides (CAPs) are crucial components of the innate immune system against bacterial pathogens.

Purpose of the Study:

  • To investigate the susceptibility of clinical Staphylococcus aureus isolates, including MRSA, to host-derived CAPs LL-37 and human beta-defensin-3 (hBD3).
  • To determine the relationship between bacterial net charge (zeta potential) and resistance to LL-37 and hBD3 in MRSA and methicillin-susceptible S. aureus (MSSA).

Main Methods:

  • Examined susceptibility of 190 MSSA and 304 MRSA clinical strains to LL-37 and hBD3.
  • Assessed zeta potential in 54 S. aureus strains to correlate with CAP susceptibility.
  • Measured percentage survival and Minimum Bactericidal Concentrations (MBCs) to confirm resistance.

Main Results:

  • MRSA strains resistant to LL-37 exhibited significantly higher zeta potentials compared to susceptible strains.
  • No significant difference in zeta potential was observed for MRSA strains resistant or susceptible to hBD3.
  • Resistance to LL-37, but not hBD3, was significantly elevated in highly methicillin-resistant S. aureus compared to MSSA.

Conclusions:

  • Increased net charge in clinical MRSA strains correlates with elevated resistance to LL-37, but not hBD3.
  • These findings highlight a potential mechanism of resistance to specific CAPs in MRSA.
  • Understanding these interactions may inform the development of novel therapeutic strategies against MRSA infections.

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