Enhanced staphylolytic activity of the Staphylococcus aureus bacteriophage vB—SauS-philPLA88 virion-associated peptidoglycan hydrolase HydH5: fusions, deletions and synergy with LysH5
The United States of America; as Represented by the Secretary of Agriculture
发明人:
David M. Donovan,Lorena Rodriguez Rubio,Beatriz Martinez Fernandez,Ana Rodriguez,Pilar Garcia Suarez
申请号：
US14621120
公开号：
US09868943B2
申请日:
2015.02.12
申请国别(地区):
US
年份:
2018
代理人:
摘要：
Virion-associated peptidoglycan hydrolases have a potential as antimicrobial agents due to their ability to lyse Gram positive bacteria on contact. Fusion proteins HydH5SH3b and HydH5Lyso comprising full-length peptidoglycan hydrolase HydH5 from the Staphylococcus aureus bacteriophage vB_SauS-phi-IPLA88 in combination with the SH3b cell wall-binding domain from lysostaphin or full length lysostaphin, respectively, exhibited high lytic activity against live S. aureus cells. CHAPSH3b, a HydH5 CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) domain from truncated HydH5 in combination with the SH3b domain of lysostaphin, exhibited the highest lytic activity against live S. aureus cells. HydH5 and its derivative fusions lysed bovine and human S. aureus, methicillin-resistant S. aureus (MRSA) N315 strain, and human S. epidermidis strains in zymogram, plate lysis and turbidity reduction assays. HydH5 and its derivative fusions displayed antimicrobial synergy with the endolysin LysH5 (also encoded by vB_SauS-phi-IPLA88) in vitro suggesting the two enzymes have distinct cut sites and thus may be more efficient in combination for elimination of staphylococcal infections.
