Comparative genomic analysis of \(\textit{Klebsiella}\) and \(\textit{E. coli}\) diversity: assessing the impacts of travel, animal husbandry practices and lifestyle

Maganga, Ruth Samson (2024). Comparative genomic analysis of \(\textit{Klebsiella}\) and \(\textit{E. coli}\) diversity: assessing the impacts of travel, animal husbandry practices and lifestyle. University of Birmingham. Ph.D.

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Abstract

Antimicrobial resistance is a significant public health problem which is further exacerbated by the increasing prevalence of resistant pathogens, particularly of bacterial origin, which cannot be effectively treated with existing antimicrobials. In East Africa this is a critical problem due to limited resources available to combat it. Currently there is very limited whole-genome sequencing (WGS) data addressing antimicrobial resistance genes (AMR) patterns and the underlying mechanisms of transfer of resistance genes. In the present study we employ WGS to shed light on the complex dynamics of AMR in Gram-negative opportunistic pathogens (\(\textit{Escherichia coli}\) and \(\textit{Klebsiella pneumoniae}\)) in East Africa. Here, AMR patterns were investigated before and after travel, in the context of animal husbandry, as well as in distinct communities with varying lifestyles. Consequently, this study provides insights into the AMR patterns in these three situations at genomic level while also contributing to the relatively scarce WGS data existing literature in East Africa.

Short-term colonisation of different \(\textit{K. pneumoniae}\) species were observed pre- and post-travel, which lead us to suggest that travel may have an impact on composition of gut microbiota. Moreover, acquisition of AMR was mostly seen in multidrug-resistant (MDR) \(\textit{Klebsiella variicola}\) strains both pre- and post-travel. Resistance genes in these strains were mainly associated with plasmids, giving weight to the important role of mobile genetic elements in the spread of AMR. Our study did not find evidence for widespread acquisition of ESBL-producing strains but found that colonization by MDR strains was common. Furthermore, the majority of \(\textit{K. variicola}\) strains were closely related, suggesting a common source and/or transmission between individuals in the study population.

In a second study, significant proportion of \(\textit{E. coli}\) strains from livestock exhibiting resistance to antimicrobials were observed, that were commonly employed in animal husbandry. Further analysis of the data revealed a higher prevalence of MDR in poultry compared to pigs. This was attributed to varying antibiotic use between the two animal husbandry systems and context-specific variation in diseases prevalence. Upon further exploration of the data, sharing of strains between animal groups were seen, revealing evidence of different AMR reservoirs being shared between poultry and pigs. These findings emphasise the importance of adopting a One Health approach that considers the well-being of different animal groups, humans, and the environment.

Further to this, \(\textit{E. coli}\) MAGs from previously published studies were reconstructed to conduct a comparative study so that we can understand the difference in gut \(\textit{E. coli}\) diversity between the Hadza and the general population in Tanzania. Three \(\textit{E. coli}\) MAGs were successfully reconstructed following metagenomic analysis of the sequences. No evidence of resistance was found and virulence genes in the identified MAGs. However, this may have been attributed to quality of the data. Further observation of the data revealed variation in genes linked aromatic amino acid metabolism between \(\textit{E. coli}\) MAGs derived from the two communities, notably the absence of \(\textit{proC}\), \(\textit{aroA}\) and \(\textit{trpD}\) genes in the Hadza.

In summary, our study emphasizes the importance of considering local conditions in AMR research. Additionally, it sheds light on the transmission of resistant bacteria between different animal species, as well as the identification of genetic elements that contribute to the spread of AMR. Our findings underscore the importance of monitoring and targeted interventions that are adapted to environments. Moreover, our study supports the adoption of a One Health approach that integrates local practices, animal care and human behaviour to combat the growing problem of AMR, in Sub Saharan Africa.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):