%0 Journal Article
%T A Novel Innate Immune-Enhancement Strategy Combined with IVIG Rescues Mice from Fatal Staphylococcus aureus Septicemia
%A Gowrisankar Rajam
%A Gabrielle M. Hammons
%A George M. Carlone
%A Jacquelyn S. Sampson
%A Edwin W. Ades
%J International Journal of Microbiology
%D 2011
%I Hindawi Publishing Corporation
%R 10.1155/2011/725483
%X Staphylococcus aureus (SA) is a major community-acquired pathogen. The emergence of drug-resistant strains like, methicillin-resistant SA (MRSA), poses stiff challenges to therapeutic intervention. Passive immune-therapy with specific antibodies is being actively examined to treat fulminant infections with limited success. In this study, we demonstrate that P4, a 28-amino acid peptide, derived from pneumococcal surface adhesin A along with pathogen-specific antibody (IVIG; P4 therapy) is successful in enhancing the opsonophagocytic killing (OPK) of S. aureus in vitro. We questioned if it is possible to expand P4 therapy to treat staphylococcal infections in vivo. P4 therapy in combination with IVIG rescued 7/10 morbidly ill S. aureus-infected mice while only 2/10 survived in the control group. 1. Introduction Staphylococcus aureus, a gram-positive bacterium, is a commensal organism known to cause a wide range of hospital- and community-acquired infections. It is also recognized for immune evasion mechanisms and its ability to develop multi-antibiotic resistance. The burden of staphylococcal disease has increased worldwide with the emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) [1, 2]. Incidence of S. aureus bacteremia in the United States ranges between 20 and 40 cases per 100,000 with the case fatality rates ranging from 19 to 24% [3]. CA-MRSA rates have doubled in USA from the year 2000 to 2006 [4]. The major threats are the increase in the drug resistance in S. aureus, the spread among community isolates, and the limited new drugs with demonstrable efficacy on the drug-resistant isolates [3]. To address these challenges, we need to develop new tools and/or to retune old tools with new techniques. Therapeutic antibodies (passive immunotherapy) which can enhance the host immune systemĄ¯s ability to overcome S. aureus infection are ideal candidates to be evaluated as alternatives to combating this infection [5]. P4, a 28-amino acid peptide derived from pneumococcal surface adhesin A, has enhanced in vitro opsonophagocytosis in the presence of pathogen-specific IgG and rescued mice from life-threatening pneumococcal infection (P4-therapy) [6¨C8]. Recently, we have shown that P4-therapy can also be used to rescue mice from serious secondary pneumococcal infection following H1N1 viral infection in mice [9]. We questioned if it is possible to use P4 therapy to treat staphylococcal infections in vivo? 2. Materials and Methods 2.1. Peptide Synthesis The amino acid sequence of the peptide designated as P4 was previously
%U http://www.hindawi.com/journals/ijmicro/2011/725483/