The Type VI Secretion system of Klebsiella pneumoniae

: a weapon for antimicrobial warfare

Abstract

The Type VI Secretion system (T6SS) is a protein secretion apparatus, utilised by Gram-negative bacteria to introduce toxins into a wide range of prey. This prey can include other bacteria within the same species, of a different species and even other eukaryotic cells. The T6SS has been shown in the case of many bacteria to contribute to host colonisation, virulence and competition with other microbes. Given that the focus of this research, Klebsiella pneumoniae, is a critical concern of the WHO, this research will contribute to the limited knowledge about Klebsiella infection biology, in a pathogen of global health concern.

The objectives of this research are therefore, to discern the functionality of the T6SS in a hypervirulent clinical isolate of K. pneumoniae Kp52145. Preliminary data from Lery et al. 2014, predicted the presence of 3 clusters of T6SS genes within the genome of Kp52145 and the main objective of this research is to characterise these clusters in the context of antibacterial competition. This includes how the T6SS of Kp52145 contributes to intraspecies/ interspecies competition and to identify molecular mechanisms by which lebsiella can compete with other bacteria. Other pertinent objectives of this research are to identify the molecular mechanisms by which mutations in specific lipid A residues can impact the function of the T6SS. A further objective is to describe a novel regulator in Klebsiella species which activates the T6SS and may define two distinct
strategies for T6SS function in K. pneumoniae. Through a bioinformatics-based approach coupled with molecular microbiology, this research contributes to the understanding of this novel bacterial virulence factors.

Date of Award	Dec 2024
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Miguel A. Valvano (Supervisor), Jose Bengoechea (Supervisor) & Paul Moynagh (Supervisor)