Human Salivary Protein Histatin 5 Has Potent Bactericidal Activity against ESKAPE Pathogens

Frontiers in Cellular and Infection Microbiology

McCall, Andrew¹  Du, Han¹  Puri, Sumant¹  Norris, Hannah L.¹  Edgerton, Mira²  Russo, Thomas³ 

[1] Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA;The Department of Medicine, University at Buffalo, Buffalo, NY, USA;Veterans Administration Western New York Healthcare System, Buffalo, NY, USA

关键词: ESKAPE;    Antimicrobial peptide;    Histatin 5;    C;    ida albicans;    bactericidal activity;   

DOI  :  10.3389/fcimb.2017.00041

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter species) 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. Histantin 5 (Hst 5) is a salivary cationic histidine-rich peptide produced only in humans and higher primates. It has high antifungal activity against Candida albicans through an energy-dependent, non-lytic process; but its bactericidal effects are less known. We found Hst 5 has bactericidal activity against S. aureus (60-70% killing) and A. baumannii (85-90% killing) in 10 mM and 100 mM sodium phosphate buffer (NaPB), while killing of >99% of P. aeruginosa, 60-80% E. cloacae and 20-60% of E. faecium was found in 10 mM NaPB. Hst 5 killed 60% of biofilm cells of P. aeruginosa, but had reduced activity against biofilms of S. aureus and A. baumannii. Hst 5 killed 20% of K. pneumonia biofilm cells but not planktonic cells. Binding and uptake studies using FITC-labeled Hst 5 showed E. faecium and E. cloacae killing required Hst 5 internalization and was energy dependent, while bactericidal activity was rapid against P. aeruginosa and A. baumannii suggesting membrane disruption. Hst 5-mediated killing of S. aureus was both non-lytic and energy independent. Additionally, we found that spermidine conjugated Hst 5 (Hst5-Spd) had improved killing activity against E. faecium, E. cloacae and A. 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.

【 授权许可】

CC BY