JAC Advance Access originally published online on March 26, 2008
Journal of Antimicrobial Chemotherapy 2008 61(6):1266-1269; doi:10.1093/jac/dkn106
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Original research |
Increased resistance to cationic antimicrobial peptide LL-37 in methicillin-resistant strains of Staphylococcus aureus
1 Department of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan 2 Department of Immunology, The Forsyth Institute, Boston, MA 02115-3799, USA 3 Department of Pathology and Laboratory Medicine, Hiroshima Prefectural Hospital, Hiroshima 734-8530, Japan 4 Department of Internal Medicine, Hiroshima Prefectural Hospital, Hiroshima 734-8530, Japan 5 Department of Dermatology, Ehime University School of Medicine, Onsen-gun, Ehime 791-0295, Japan
Received 13 September 2007; returned 13 December 2007; revised 10 February 2008; accepted 20 February 2008
* Corresponding author. Tel: +81-99-275-6150; Fax: +81-99-275-6158; E-mail: hkomatsu{at}denta.hal.kagoshima-u.ac.jp
Objectives: 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 β-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.
Keywords: cathelicidin family peptide , human β-defensin , clinical isolates , antibiotic susceptibility , innate immunity
Present address: Department of Oral Microbiology, Kagoshima University, Graduate School of Medicine and Dental Services, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
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