title: A novel C5a-derived immunobiotic peptide reduces Streptococcus agalactiae colonization through targeted bacterial killing.
abstract: Streptococcus agalactiae (group B Streptococcus [GBS]) is a Gram-positive bacterium that colonizes the cervicovaginal tract in approximately 25% of healthy women. Although colonization is asymptomatic, GBS can be vertically transmitted to newborns peripartum, causing severe disease such as pneumonia and meningitis. Current prophylaxis, consisting of late gestation screening and intrapartum antibiotics, has failed to completely prevent transmission, and GBS remains a leading cause of neonatal sepsis and meningitis in the United States. Lack of an effective vaccine and emerging antibiotic resistance necessitate exploring novel therapeutic strategies. We have employed a host-directed immunomodulatory therapy using a novel peptide, known as EP67, derived from the C-terminal region of human complement component C5a. Previously, we have demonstrated in vivo that EP67 engagement of the C5a receptor (CD88) effectively limits staphylococcal infection by promoting cytokine release and neutrophil infiltration. Here, using our established mouse model of GBS vaginal colonization, we observed that EP67 treatment results in rapid clearance of GBS from the murine vagina. However, this was not dependent on functional neutrophil recruitment or CD88 signaling, as EP67 treatment reduced the vaginal bacterial load in mice lacking CD88 or the major neutrophil receptor CXCr2. Interestingly, we found that EP67 inhibits GBS growth in vitro and in vivo and that antibacterial activity was specific to Streptococcus species. Our work establishes that EP67-mediated clearance of GBS is likely due to direct bacterial killing rather than to enhanced immune stimulation. We conclude that EP67 may have potential as a therapeutic to control GBS vaginal colonization.
authors: Department of Biology and Center for Microbial Sciences, San Diego State University, San Diego, California, USA.
authors: Courtney K
authors: CK
authors: Cavaco
authors: Kathryn A
authors: KA
authors: Patras
authors: Jaime E
authors: JE
authors: Zlamal
authors: Marilyn L
authors: ML
authors: Thoman
authors: Edward L
authors: EL
authors: Morgan
authors: Sam D
authors: SD
authors: Sanderson
authors: Kelly S
authors: KS
authors: Doran
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D015169:Colony Count, Microbial; D015936:Complement C5a / Q000737:chemistry*; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000276:immunology; D060737:Reproductive Tract Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D013045:Species Specificity; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000187:drug effects* / Q000254:growth & development; D014621:Vagina / Q000187:drug effects / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D044087:Receptor, Anaphylatoxin C5a; D023063:Receptors, Interleukin-8B; D015936:Complement C5a
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