The Gut Bacterium Bacteroides thetaiotaomicron Influences the Virulence Potential of the Enterohemorrhagic Escherichia coli O103:H25

Abstract

Enterohemorrhagic E. coli (EHEC) is associated with severe gastrointestinal disease. Upon entering the gastrointestinal tract, EHEC is exposed to a fluctuating environment and a myriad of other bacterial species. To establish an infection, EHEC strains have to modulate their gene expression according to the GI tract environment. In order to explore the interspecies interactions between EHEC and an human intestinal commensal, the global gene expression profile was determined of EHEC O103:H25 (EHEC NIPH-11060424) co-cultured with B. thetaiotaomicron (CCUG 10774) or grown in the presence of spent medium from B. thetaiotaomicron. Microarray analysis revealed that approximately 1% of the EHEC NIPH-11060424 genes were significantly up-regulated both in co-culture (30 genes) and in the presence of spent medium (44 genes), and that the affected genes differed between the two conditions. In co-culture, genes encoding structural components of the type three secretion system were among the most affected genes with an almost 4-fold up-regulation, while the most affected genes in spent medium were involved in chemotaxis and were more than 3-fold up-regulated. The operons for type three secretion system (TTSS) are located on the Locus of enterocyte effacement (LEE) pathogenicity island, and qPCR showed that genes of all five operons (LEE1-LEE5) were up-regulated. Moreover, an increased adherence to HeLa cells was observed in EHEC NIPH-11060424 exposed to B. thetaiotaomicron. Expression of stx2 genes, encoding the main virulence factor of EHEC, was down-regulated in both conditions (co-culture/spent medium). These results show that expression of EHEC genes involved in colonization and virulence is modulated in response to direct interspecies contact between cells, or to diffusible factors released from B. thetaiotaomicron. Such interspecies interactions could allow the pathogen to recognize its predilection site and modulate its behaviour accordingly, thus increasing the efficiency of colonization of the colon mucosa, facilitating its persistence and increasing its virulence potential.

Coculture of Escherichia coli O157:H7 with a Nonpathogenic E. coli Strain Increases Toxin Production and Virulence in a Germfree Mouse Model

“…A further exploration of the interactions between E. coli O157:H7 and the plethora of bacterial species present in the gut is needed to appreciate how the gut microbiome affects the virulence of this foodborne pathogen. It was also shown previously that fecal Bacteroides thetaiotaomicron alters Stx2 expression (40)(41)(42), although two studies (40,42) report decreases while one (41) report shows Hematoxylin-and eosin-stained renal sections from mice infected with either C600 or PA2 and PA2 plus C600. The mice were scored as described in Materials and Methods.…”

Modulation of Enterohaemorrhagic Escherichia coli Survival and Virulence in the Human Gastrointestinal Tract

“…This is mediated by inhibition of the lytic cycle via the SOS response regulator RecA. Interestingly, similar results were obtained when EHEC O157:H7 was cultured in medium conditioned by the predominant species of the Bacteroides phylum B. thetaiotaomicron only [108,118]. Furthermore, Cordonnier and colleagues demonstrated that reduced Stx2 production was dependent on internalization of vitamin B 12 by B. thetaiotaomicron as a mutant deficient in an outer membrane receptor of vitamin B 12 was unable to repress the Stx2 production.…”

“…Several studies have shown that Lactobacillus and Bifidobacterium species decrease EHEC adhesion to intestinal epithelial cells in vitro by different mechanisms including direct competition for binding sites at the enterocyte surface [97,98,99,100,101], production of molecules modulating expression of adhesins [102,103,104] and stimulation of mucus production, thereby preventing access to the epithelial surface [105,106]. Conversely, in vitro co-culture of EHEC O157:H7 and O103:H25 and the commensal strain Bacteroides thetaiotaomicron led to increased expression of all LEE operons [107,108], increased epithelial adhesion and formation of A/E lesions. The same effect was observed following co-incubation of EHEC O157:H7 and Enterococcus faecalis , a commensal strain belonging to the phylum Firmicutes [107].…”

Distinctive Gut Microbiota Is Associated with Diarrheagenic Escherichia coli Infections in Chilean Children

“…Bacteroides tethaiotaomicron , a predominant member of the gut microbiota in healthy subjects, enhanced the expression of several genes of STEC reference strain in co-culture experiments, including virulence genes located in the LEE pathogenicity island. Moreover, an increase of A/E lesions and STEC adherence to epithelial cells was found (Curtis et al, 2014 ; Iversen et al, 2015 ). Considering the above, further studies should focus on the role of species described here as indicative of DEC group in the pathogenicity of DEC pathotypes.…”

“…However, this phenomenon is not completely understood for DEC, as most studies have focused on molecular mechanism occurring inside the bacteria, with only a few evaluating environmental factors, such as, gut microbiota (Pacheco and Sperandio, 2015 ; Singh et al, 2015 ). In the last years, several groups have focused on the role components of the gut microbiota and its association with diarrheal disease caused by enteric pathogens, including DEC strains (Nelson et al, 2012 ; Curtis et al, 2014 ; Iversen et al, 2015 ; Lindsay et al, 2015 ).…”