Y. enterocolitica is a human pathogen that cause mostly food-borne yersiniosis, usually a diarrheal disease sometimes followed by post-infectious reactive arthritis. Yersiniosis is considered to be the third most common cause of gastroenteritis in Europe. In Finland both Y. pseudotuberculosis and Y. enterocolitica cause hundreds of human infections annually. The aim of the study is to characterize the intricate regulatory networks of Yersinia especially those that control the expression of the virulence factors. To achieve that goal three regulators (YbeY, RfaH and Hfq) were initially selected. The absence of ybeY gene in Y. enterocolitica serotype O:3 resulted in misprocessing of 16S rRNA, severe decrease of growth rate, disturbed regulation of the Yersinia virulence plasmid genes expression and affected the expression of small RNAs. Furthermore, the ybeY mutant displayed impairment of many virulence-related features, and decreased infectivity in the cell infection model. The study revealed that RfaH of Y. enterocolitica O:3 acts as a highly specific regulator that enhances the transcription of selected operons involved in biosynthesis of lipopolysaccharide. Furthermore, the transcriptomics study indicated that some changes seen in the rfaH mutant strain were actually due to indirect responses to the loss of O-antigen. Moreover, the lack of RfaH resulted in attenuated stress response and lower resistance to selected chemical compounds. The loss of Hfq caused impairment in growth, elongation of the bacterial cells, and decreased the resistance of bacteria to heat, acid and oxidative stresses, as well as attenuation in mouse infection experiments. Moreover, this study revealed that several alterations typical for the hfq-negative phenotype were due to derepression of the transcriptional factor RovM. In conclusion, all the studied mutations caused different alterations in gene regulatory networks and eventually led to a compromise in the virulence of Y. enterocolitica O:3. The studied mutants showed significant decrease in resistance to different environmental conditions and alterations in the bacterial physiology that contribute to vitality and ability to establish infection in host organism.
|Status||Publicerad - 2016|
|MoE-publikationstyp||G5 Doktorsavhandling (artikel)|
- 3111 Biomedicinska vetenskaper