1887

Abstract

is a Gram-negative, murine-specific enteric pathogen that infects epithelial cells in the colon. It is closely related to the clinically relevant human pathogen, enterohemorrhagic (EHEC), a leading cause of haemorrhagic colitis and haemolytic uremic syndrome. We have previously reported that a novel antimicrobial peptide, wrwycr, compromises bacterial DNA repair and significantly reduces the survival of acid-stressed EHEC, suggesting an antimicrobial strategy for targeting the survival of ingested EHEC. This study examines the impact of peptide pretreatment on survival of the closely related murine pathogen, , before and after acid stress, using both and investigations. Peptide pretreatment of significantly and dramatically increases acid-stress-induced killing in a peptide-dose-dependent and time-dependent manner. Reduction in survival rates after brief pretreatment with peptide (25–65 µM) followed by 1 h at pH 3.5 ranges from 6 to 8 log fold relative to untreated , with no detectable bacteria after 65 µM peptide-acid treatment. Using a C57BL/6 mouse model of infection, peptide pretreatment of with wrwycr prior to orogastric gavage eliminates evidence of infection based on colonization levels, faecal scores, colonic histology, faecal microbiome and visual observation of overall animal health. These findings provide compelling evidence for the role of the peptide wrwycr as a potential strategy to control the growth and colonization of enteric pathogens.

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2016-09-01
2020-04-07
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