New antimicrobials to target gut and food pathogens

There is a pressing need for the discovery of new antimicrobials to fight antibiotic resistant bacteria. The aim of this thesis was the discovery and characterisation of new bacteriocins from two sources, fermented foods and human faeces, testing the hypothesis that bacteria from the same niche will produce antimicrobials uniquely suited to act in this niche. Isolates from culture collections and new isolates from food and faecal samples were screened against a panel of pathogens responsible for food spoilage and human disease. Promising candidates were selected for genome sequencing, antimicrobial characterisation and biological study. The genome of Lactobacillus gasseri LM19 showed the presence of antimicrobial genes encoding, among others, a new bacteriocin, gassericin M. L. gasseri LM19 could survive and express its bacteriocin genes under colonic conditions. Its administration modulated the effects of Clostridium perfringens on the gut microbiota composition. Streptococcus agalactiae DPC7040 was previously shown to produce the natural variant nisin P. MALDI-ToF analysis confirmed that nisin P is three amino acids shorter than nisin A and that two lanthionine rings were absent in 50% of molecules. This structure impacted on its antimicrobial activity, which was weaker than that of nisin A and nisin H in faecal fermentations. Staphylococcus epidermidis strains isolated from faecal samples were compared with skin isolates with respect to genomic and phenotypic traits. It was concluded that S. epidermidis has no specific genomic features to colonise different body sites but is likely to adapt its metabolism to the different conditions. Potential novel antimicrobials were found in Lactobacillus amylovorus and Lactobacillus crispatus isolates, which showed probiotic properties and interesting phenotypic differences between strains. Together, this work further demonstrates that fermented food and gut environments are valuable sources of new isolates, the study of which can yield new antimicrobials and give insights into bacterial ecology and evolution.