Local Inflammation Exacerbates the Severity of Staphylococcus aureus Skin Infection

Department of Pediatrics, University of Chicago, Chicago, Illinois, United States of America.
PLoS ONE (Impact Factor: 3.23). 07/2013; 8(7):e69508. DOI: 10.1371/journal.pone.0069508
Source: PubMed


Staphylococcus aureus is the leading cause of skin infections. In a mouse model of S. aureus skin infection, we found that lesion size did not correlate with bacterial burden. Athymic nude mice had smaller skin lesions that contained lower levels of myeloperoxidase, IL-17A, and CXCL1, compared with wild type mice, although there was no difference in bacterial burden. T cell deficiency did not explain the difference in lesion size, because TCR βδ (-/-) mice did not have smaller lesions, and adoptive transfer of congenic T cells into athymic nude mice prior to infection did not alter lesion size. The differences observed were specific to the skin, because mortality in a pneumonia model was not different between wild type and athymic nude mice. Thus, the clinical severity of S. aureus skin infection is driven by the inflammatory response to the bacteria, rather than bacterial burden, in a T cell independent manner.

Download full-text


Available from: Anita Chong, Jan 16, 2015
19 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The therapeutic efficacy of two novel short antimicrobial and anti-inflammatory peptides (RR and RRIKA) was evaluated in a mouse model of staphylococcal skin infection. RR (2%) and RRIKA (2%) significantly reduced the bacterial counts and the levels of proinflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, in methicillin-resistant Staphylococcus aureus USA 300-0114 skin lesions. Furthermore, the combined therapy of RRIKA (1%) and lysostaphin (0.5%) had significantly higher antistaphylococcal and anti-inflammatory activity compared to monotherapy. This study supports the potential use of these peptides for topical treatment of methicillin-resistant Staphylococcus aureus skin infections.
    Drug Design, Development and Therapy 10/2014; 8:1979-83. DOI:10.2147/DDDT.S72129 · 3.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Staphylococcus aureus (S. aureus) is a virulent bacterium that abundantly colonizes inflammatory skin diseases. Since S. aureus infections occur in an impaired skin barrier, it is important to understand the protective mechanism through cutaneous immune responses against S. aureus infections and the interaction with Staphylococcal virulence factors. In this review, we summarize not only the pathogenesis and key elements of S. aureus skin infections, but also the cutaneous immune system against its infections and colonization. The information obtained from this area may provide the groundwork for further immunomodulatory therapies or vaccination strategies to prevent S. aureus infections.
    03/2014; 4(1):39-46. DOI:10.15280/jlm.2014.4.1.39
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The seriousness of microbial resistance combined with the lack of new antimicrobials have increased the interest in the development of antimicrobial peptides (AMPs) as novel therapeutics. In this study, we evaluated the antimicrobial activity of two short synthetic peptides, namely RRIKA and RR. These peptides exhibited potent antimicrobial activity against Staphylococcus aureus and their antimicrobial effects were significantly enhanced by addition of three amino acids in the C terminus, which consequently increased the amphipathicity, hydrophobicity and net charge. Moreover, RRIKA and RR demonstrated a significant and rapid bactericidal effect against clinical and drug-resistant Staphylococcus isolates including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), vancomycin-resistant S. aureus (VRSA), linezolid-resistant S. aureus and methicillin-resistant S. epidermidis. In contrast to many natural AMPs; RRIKA and RR retained their activity in the presence of physiological concentrations of NaCl and MgCl2. Both RRIKA and RR enhanced the killing of lysostaphin over 1000-fold and eradicated MRSA and VRSA isolates within 20 minutes. Furthermore, the peptides presented were superior in reducing adherent biofilms of S. aureus and S. epidermidis when compared to conventional antibiotics. Our findings indicate that the staphylocidal effects of our peptides were through permeabilization of the bacterial membrane, leading to leakage of cytoplasmic contents and cell death. Furthermore, peptides were not toxic to HeLa cells at 4 to 8 fold their antimicrobial concentrations. The potent and salt-insensitive antimicrobial activities of these peptides present an attractive therapeutic candidate for treatment of multidrug-resistant S. aureus infections.
    Antimicrobial Agents and Chemotherapy 05/2014; 58(7). DOI:10.1128/AAC.02578-14 · 4.48 Impact Factor
Show more