Affiliation:
1. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
2. Laboratory of Bacterial Pathogenesis and Antimicrobial Resistance, Veterans Affairs Medical Center, Decatur, Georgia 30033
Abstract
ABSTRACT
Polyamines are biogenic polycationic molecules involved in key cellular functions. Extracellular polyamines found in bodily fluids or laboratory media can be imported by bacteria or bind to negatively charged bacterial surface structures, where they can impair binding of antimicrobials. We hypothesized that the presence of polyamines in fluids that bathe urogenital mucosal surfaces could alter the susceptibility of the sexually transmitted strict human pathogen
Neisseria gonorrhoeae
to mediators of the innate host defense. Herein we report that polyamines can significantly increase gonococcal resistance to two structurally diverse cationic antimicrobial peptides (polymyxin B and LL-37) but not to antibiotics that exert activity in the cytosol or periplasm (e.g., ciprofloxacin, spectinomycin, or penicillin). The capacity of polyamines to increase gonococcal resistance to cationic antimicrobial peptides was dose dependent, correlated with the degree of cationicity, independent of a polyamine transport system involving the polyamine permeases PotH and PotI, and was reversible. In addition, we found that polyamines increase gonococcal resistance to complement-mediated killing by normal human serum. We propose that polyamines in genital mucosal fluids may enhance gonococcal survival during infection by reducing bacterial susceptibility to host-derived antimicrobials that function in innate host defense.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference39 articles.
1. Bourgeon, F., B. Evrard, M. Brillard-Bourdet, D. Colleu, B. Jegou, and C. Pineau. 2004. Involvement of semenogelin-derived peptides in the antibacterial activity of human seminal plasma. Biol. Reprod.70:768-774.
2. Genetics of Serum Resistance in
Neisseria gonorrhoeae
: The
sac-1
Genetic Locus
3. Regulation of
mtrF
Expression in
Neisseria gonorrhoeae
and Its Role in High-Level Antimicrobial Resistance
4. Griffiss, J. M., G. A. Jarvis, J. P. O'Brien, M. M. Eads, and H. Schneider. 1991. Lysis of Neisseria gonorrhoeae initiated by binding of normal human IgM to a hexosamine-containing lipooligosaccharide epitope(s) is augmented by strain-specific, properdin-binding-dependent alternative complement pathway activation. J. Immunol.147:298-305.
5. Hall, S. H., K. G. Hamil, and F. S. French. 2002. Host defense proteins of the male reproductive tract. J. Androl.23:585-597.
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