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The mucosal surface in the intestinal tract is a complex ecosystem composed of gastrointestinal epithelium, immune cells and resident bacterial flora. In this environment, bacteria are either in get in touch with with intestinal surfaces or embedded in hostproduced mucus [1]. Genome-wide analyses performed on intestinal microbiota provided insights into useful metabolic activities following establishment of productive commensal or symbiotic relationships together with the host [4]. These studies also showed that the absence of an intact microbiota drastically increases susceptibility to pathogens, underlining the truth that colonization of mucosa and competition with commensal bacterial flora is often the initial step in most intestinal infections [80]. This long-known but ill-understood protection offered by commensals against pathogens is typically described as being colonization resistance, the barrier impact, bacterial antagonism orbacterial interference [1,103]. Numerous mechanisms have been proposed for explaining colonization resistance, which includes: direct competition for nutrients; prevention of access to adherence web pages; limitation of pathogen proliferation by means of production of inhibitory substances or situations; or stimulation of host natural immune defenses [10,14,15]. However, the complexity of bacterial interactions inside the host and the absence of relevant models has severely hindered identification of molecular facts on how commensal bacteria interfere with pathogens [13,16]. Due to these shortcomings, evaluation of competitive bacterial interactions that contribute to restricting pathogen establishment inside the intestinal flora has almost exclusively focused on secreted inhibitory substances (colicins, microcins, toxins) developed in liquid or strong medium or brought to light in competitors experiments performed lots of decades ago [13].Anacetrapib Lately, interest in bacterial group behavior drew attention to biofilms, swarms, aggregates and dense bacterial cultures asPLOS A single | www.Osilodrostat (phosphate) plosone.PMID:23746961 orgColonization Resistance in E. coli Biofilmsmodels for studying competitive and synergistic interactions [1726]. Indeed, contemplating the biofilm-like structure of vertebrate bacterial flora, controlled biofilm communities could allow direct experimental investigations of some aspects of molecular events leading to pathogen establishment in a multispecies context [16,27,28]. Right here we’ve developed an in vitro-to-in vivo method to studying colonization resistance. We made use of dynamic and controlled mixed in vitro biofilm models to investigate how populations of commensal Escherichia coli, a predominant facultative anaerobe with the intestinal microbiota, are colonized by a pathogenic diarrheagenic enteroaggregative E. coli [9,29,30]. Gene expression profiling demonstrated that pathogen entry into commensal biofilm triggers certain genetic responses, a number of them also induced upon colonization by an unrelated bacterial pathogen, Klebsiella pneumoniae. Systematic functional evaluation led to identification of genes involved in stopping incoming pathogens from settling and increasing inside commensal biofilm. Finally, we explored the in vivo relevance of a subset of identified colonization resistance genes and demonstrated their implication in manage of the commensal/ pathogen ratio within the mouse gut environment. This study hence provides new concepts and procedures for investigating.
