Investigating the association between short chain fatty acid antimicrobials and Escherichia coli virulence

Fallata, Ghaith Mohammed (2023) Investigating the association between short chain fatty acid antimicrobials and Escherichia coli virulence. PhD thesis, University of Glasgow.

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Antibiotic resistance in bacteria is often attributed to the excessive use of antibiotics in the agricultural and food processing sectors. Globally, antibiotics are also widely used as growth supplements in livestock, and this practice has led to an increase in multidrug-resistant microbes, raising concerns regarding the use of human-use antibiotics in livestock and food-producing animals. Due to their desirable properties, antibiotic alternatives such as organic acids have recently replaced antibiotics as antimicrobials and preventatives. As a breakdown product of non-digestible carbohydrates, some organic acids, such as propionic acid (PA) and formic acid (FA), are naturally present in the human and animal guts, and they serve crucial roles in regulating the host immune responses.

Moreover, a study revealed that long-term exposure of adherent-invasive Escherichia coli (AIEC), a bacterial pathotype linked with Crohn's disease, to PA significantly altered its phenotype, resulting in enhanced adherence and invasion of epithelial cells and increased persistence through biofilm formation. In addition, it remains unclear what makes AIEC pathogenic, but it was proposed that environmental factors such as organic acids have a role in altering AIEC phenotype which could make the strains more pathogenic. Therefore, organic acids and alterations of the AIEC phenotype were investigated. Since AIEC is evolutionarily and phylogenetically related to avian pathogenic Escherichia coli (APEC), and APEC strains are more often exposed to organic acids such as PA and FA due to their widespread use in feeds, the impact of FA and PA on APEC strains was also investigated.

In the investigation of organic acids and their association with phenotypic alteration of AIEC and APEC, several methods were used, such as Next-Generation Sequencing and an in vitro fermentation gut model, along with several assays to determine organic acids effects. The results revealed that PA can alter the phenotype of AIEC and increase its virulence in traits such as adhesion, invasion and biofilm formation. In addition, AIEC adapted to PA showed a significant increase in net replication within immune cells when ethanolamine is present, ethanolamine being a carbon source that becomes increasingly available during intestinal inflammation. However, FA has a different effect on AIEC and APEC strains. The gene expression of AIEC adapted to FA revealed that FA has inhibitory effects in contrast to PA. Additionally, an in vitro fermentation gut model indicated that more E. coli can be recovered from the fermentation when PA is present as opposed to FA.

In conclusion, organic acids can alter AIEC and APEC phenotypes, and some of these alterations could lead to the emergence of virulent strains of bacteria. The finding that PA increased the virulence of AIEC raises concerns about its long-term effects since it is used as an antibacterial in various food and agricultural sectors. Also, the findings show that FA is a more effective antibacterial for E. coli. However, APEC strains responded differently to the FA, meaning additional research is required to identify specific FA effects on APEC strains.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Supervisor's Name: Wall, Dr. Daniel
Date of Award: 2023
Depositing User: Theses Team
Unique ID: glathesis:2023-83533
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 13 Apr 2023 13:20
Last Modified: 13 Apr 2023 13:22
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