title: Human Salivary Protein Histatin 5 Has Potent Bactericidal Activity against ESKAPE Pathogens.
abstract: ESKAPE (Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumanni,Pseudomonas aeruginosa, andEnterobacterspecies) pathogens have characteristic multiple-drug resistance and cause an increasing number of nosocomial infections worldwide. Peptide-based therapeutics to treat ESKAPE infections might be an alternative to conventional antibiotics. Histatin 5 (Hst 5) is a salivary cationic histidine-rich peptide produced only in humans and higher primates. It has high antifungal activity againstCandida albicansthrough an energy-dependent, non-lytic process; but its bactericidal effects are less known. We found Hst 5 has bactericidal activity againstS. aureus(60-70% killing) andA. baumannii(85-90% killing) in 10 and 100 mM sodium phosphate buffer (NaPB), while killing of >99% ofP. aeruginosa, 60-80%E. cloacaeand 20-60% ofE. faeciumwas found in 10 mM NaPB. Hst 5 killed 60% of biofilm cells ofP. aeruginosa, but had reduced activity against biofilms ofS. aureusandA. baumannii. Hst 5 killed 20% ofK. pneumoniabiofilm cells but not planktonic cells. Binding and uptake studies using FITC-labeled Hst 5 showedE. faecium and E. cloacaekilling required Hst 5 internalization and was energy dependent, while bactericidal activity was rapid againstP. aeruginosaandA. baumanniisuggesting membrane disruption. Hst 5-mediated killing ofS. aureuswas both non-lytic and energy independent. Additionally, we found that spermidine conjugated Hst 5 (Hst5-Spd) had improved killing activity againstE. faecium, E. cloacae, andA. baumannii. Hst 5 or its derivative has antibacterial activity against five out of six ESKAPE pathogens and may be an alternative treatment for these infections.
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo Buffalo, NY, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Du
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo Buffalo, NY, USA.
authors.forename: Sumant
authors.initials: S
authors.lastname: Puri
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo Buffalo, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: McCall
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo Buffalo, NY, USA.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Norris
authors.affiliation: Veterans Administration Western New York Healthcare SystemBuffalo, NY, USA; The Department of Medicine, University at BuffaloBuffalo, NY, USA; Department of Microbiology and Immunology, University at BuffaloBuffalo, NY, USA; The Witebsky Center for Microbial Pathogenesis, University at BuffaloBuffalo, NY, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Russo
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo Buffalo, NY, USA.
authors.forename: Mira
authors.initials: M
authors.lastname: Edgerton
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000502:physiology; D054808:Histatins / Q000378:metabolism*; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; C068075:HTN3 protein, human; D054808:Histatins
keywords: Candida albicans; ESKAPE; Histatin 5; antimicrobial peptide; bactericidal activity