Inhibition of Helicobacter pylori growth by Actinomyces oris and the implications for gastric carcinogenesis

Alfawaz, Dana (2023). Inhibition of Helicobacter pylori growth by Actinomyces oris and the implications for gastric carcinogenesis. University of Birmingham. Ph.D.

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Abstract

H. pylori infection is the causative agent of intestinal-type gastric adenocarcinoma. The emergence of multidrug resistant H. pylori strains increases the burden of H. pylori infection and decreases the effectiveness of the current antimicrobial treatments. H. pylori abundance in the stomach decreases with the progression to gastric adenocarcinoma and is replaced by other members of the gastrointestinal tract and oral microbiome, including Actinomyces oris. The aim of this project was to understand the interaction between H. pylori and A. oris in vitro using co-culture systems. An oral A. oris isolate completely inhibited H. pylori in a co-culture assay and significantly decreased the growth of the related bacterium, Campylobacter jejuni. A gastric A. oris isolate and Actinomyces viscosus also inhibited H. pylori growth. The inhibition was shown to be mediated by two or more secreted factors of molecular weights both lower and higher than 5 kDa. These inhibitors are heat-resistant, acid-independent, sensitive to proteolytic activity and secreted in the stationary phase of growth. A. oris culture supernatant did not affect the growth of a panel of Gram-positive and Gram-negative bacterial species. Mass spectrometry analysis of A. oris culture supernatant revealed that it contains a 34 kDa protein of an uncharacterised function that has a lysozyme domain and a G5 domain. Analysis of the genomes of the Actinomyces strains used in the study with AntiSMASH and BAGEL4 databases indicates that they harbour putative biosynthetic gene clusters of three bacteriocins; Linocin_M18, Lanthipeptide and Sactipeptide. In conclusion, Actinomyces species produce inhibitors of H. pylori growth. Further work should focus on conclusive identification of the inhibitor and exploiting its potential as a novel antimicrobial against H. pylori infection.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):