New antimicrobials to target gut and food pathogens

Garcia-Gutierrez, Enriqueta (2019) New antimicrobials to target gut and food pathogens. Doctoral thesis, University of East Anglia.

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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.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Katherine Whittaker
Date Deposited: 14 Feb 2020 09:42
Last Modified: 14 Feb 2020 09:42


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