Role of mucus-bacteria interactions in Enterotoxigenic Escherichia coli (ETEC) H10407 virulence and interplay with human microbiome

Abstract

The intestinal mucus layer has a dual role in human health constituting a well-known microbial niche that supports gut microbiota maintenance but also acting as a physical barrier against enteric pathogens. Enterotoxigenic Escherichia coli (ETEC), the major agent responsible for traveler’s diarrhea, is able to bind and degrade intestinal mucins, representing an important but understudied virulent trait of the pathogen. Using a set of complementary in vitro approaches simulating the human digestive environment, this study aimed to describe how the mucus microenvironment could shape different aspects of the human ETEC strain H10407 pathophysiology, namely its survival, adhesion, virulence gene expression, interleukin-8 induction and interactions with human fecal microbiota. Using the TNO gastrointestinal model (TIM-1) simulating the physicochemical conditions of the human upper gastrointestinal (GI) tract, we reported that mucus secretion and physical surface sustained ETEC survival, probably by helping it to face GI stresses. When integrating the host part in Caco2/HT29-MTX co-culture model, we demonstrated that mucus secreting-cells favored ETEC adhesion and virulence gene expression, but did not impede ETEC Interleukin-8 (IL-8) induction. Furthermore, we proved that mucosal surface did not favor ETEC colonization in a complex gut microbial background simulated in batch fecal experiments. However, the mucus-specific microbiota was widely modified upon the ETEC challenge suggesting its role in the pathogen infectious cycle. Using multi-targeted in vitro approaches, this study supports the major role played by mucus in ETEC pathophysiology, opening avenues in the design of new treatment strategies.

Animal and In Vitro Models as Powerful Tools to Decipher the Effects of Enteric Pathogens on the Human Gut Microbiota

“…Caco-2, HT-29-MTX, T84, LS174T, and CCD 841 CoN are the most used cell lines for gastrointestinal in vitro models due to their specific properties [ 21 ]. For instance, Caco-2 and HT-29 cells, the latter able to secrete mucus, were co-cultured in the presence of enterotoxigenic E. coli (ETEC) H10407 to investigate the role of mucus in inducing and shaping ETEC gene expression [ 22 ]. The same cell lines were also used to test the effect of conditioned media and microbial by-products from in vitro-cultured microbiota on the human host mimicking intestinal inflammation and cell immunomodulation [ 23 ].…”

“…As regards ETEC, two in vitro models mimicking the intestinal mucosa were developed to selectively decipher the E. coli interactions with cultured mucus-adhering microbes [ 22 , 38 ]. The colonic mucus-associated microbiota of piglets was cultured in the MPigut-IVM system in the presence of the ETEC strain Ec105 [ 38 ].…”

Nanoarchitectonics of Bactericidal Coatings Based on CaCO3–Nanosilver Hybrids

“… 48 Mucin also promoted the growth of E. coli and P. aeruginosa as it can work as an additional energy source for these bacteria. 49 − 51 In the case of unloaded CaCO 3 , it did not considerably affect the growth of E. coli and P. aeruginosa . On the other hand, it promoted a reduction in the number of viable MRSA bacteria (41% less than the control).…”

“…coli and P. aeruginosa as it can work as an additional energy source for these bacteria. − In the case of unloaded CaCO 3 , it did not considerably affect the growth of E. coli and P.…”

Phage-encoded carbohydrate-interacting proteins in the human gut

“…StcE mediates EHEC pathogenesis by harshly degrading mucins in the mucosal lining of the human gut, exposing the epithelia to the pathogen (Grys et al, 2005). Other pathogens express similar virulent mucinases that contribute to disease states (Sauvaitre et al, 2022).…”