Increased resistance to cationic antimicrobial peptide LL-37 in methicillin-resistant strains of Staphylococcus aureus.
OBJECTIVE
The susceptibility of clinical isolates of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), to host-derived cationic antimicrobial peptides was investigated.


METHODS
We examined the susceptibility of 190 clinical strains of methicillin-susceptible S. aureus (MSSA) and 304 strains of MRSA to two different classes of cationic antimicrobial peptides: LL-37 and human beta-defensin-3 (hBD3). Out of the total 494 clinical strains, a random selection of 54 S. aureus strains was examined to establish the relationship between the net charge, or zeta potential, of each strain and its susceptibility to hBD3 or LL-37. To further confirm bacterial susceptibility to either hBD3 or LL-37, we concurrently measured: (i) percentage survival after in vitro bacterial exposure and (ii) MBCs for both MRSA and MSSA strains.


RESULTS
Of the 54 randomly selected S. aureus strains, those MRSA strains resistant to LL-37 showed significantly higher zeta potentials than those susceptible to LL-37 (P < 0.05). In contrast, there was no difference in bacterial zeta potentials for MRSA strains that showed either resistance or susceptibility to hBD3. In addition, resistance to LL-37, but not to hBD3, as determined by either percentage survival or MBC, was significantly elevated in highly methicillin-resistant strains of S. aureus when compared with MSSA strains (P < 0.01).


CONCLUSIONS
Clinical strains of MRSA, but not MSSA, that demonstrated an increased net charge also showed elevated resistance to LL-37, but not to hBD3.
Ouhara
Kazuhisa
K
Department of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Komatsuzawa
Hitoshi
H
Kawai
Toshihisa
T
Nishi
Hiromi
H
Fujiwara
Tamaki
T
Fujiue
Yoshihiro
Y
Kuwabara
Masao
M
Sayama
Koji
K
Hashimoto
Koji
K
Sugai
Motoyuki
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D023083:beta-Defensins / Q000494:pharmacology; D054804:Cathelicidins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C422950:DEFB103A protein, human; D023083:beta-Defensins; D054804:Cathelicidins