Conventional wisdom holds that microbes support their growth in vertebrate hosts by exploiting a large variety of nutrients. We show here that use of a specific nutrient (ethanolamine) confers a marked growth advantage on Salmonella enterica serovar Typhimurium ( S. Typhimurium) in the lumen of the inflamed intestine. In the anaerobic environment of the gut, ethanolamine supports little or no growth by fermentation. However, S. Typhimurium is able to use this carbon source by inducing the gut to produce a respiratory electron acceptor (tetrathionate), which supports anaerobic growth on ethanolamine. The gut normally converts ambient hydrogen sulfide to thiosulfate, which it then oxidizes further to tetrathionate during inflammation. Evidence is provided that S. Typhimurium's growth advantage in an inflamed gut is because of its ability to respire ethanolamine, which is released from host tissue, but is not utilizable by competing bacteria. By inducing intestinal inflammation, S. Typhimurium sidesteps nutritional competition and gains the ability to use an abundant simple substrate, ethanolamine, which is provided by the host.

Helicobacter hepaticus causes chronic hepatitis and liver cancer in mice. It is the prototype enterohepatic Helicobacter species and a close relative of Helicobacter pylori, also a recognized carcinogen. Here we report the complete genome sequence of H. hepaticus ATCC51449. H. hepaticus has a circular chromosome of 1,799,146 base pairs, predicted to encode 1,875 proteins. A total of 938, 953, and 821 proteins have orthologs in H. pylori, Campylobacter jejuni, and both pathogens, respectively. H. hepaticus lacks orthologs of most known H. pylori virulence factors, including adhesins, the VacA cytotoxin, and almost all cag pathogenicity island proteins, but has orthologs of the C. jejuni adhesin PEB1 and the cytolethal distending toxin (CDT). The genome contains a 71-kb genomic island (HHGI1) and several genomic islets whose G؉C content differs from the rest of the genome. HHGI1 encodes three basic components of a type IV secretion system and other virulence protein homologs, suggesting a role of HHGI1 in pathogenicity. The genomic variability of H. hepaticus was assessed by comparing the genomes of 12 H. hepaticus strains with the sequenced genome by microarray hybridization. Although five strains, including all those known to have caused liver disease, were indistinguishable from ATCC51449, other strains lacked between 85 and 229 genes, including large parts of HHGI1, demonstrating extensive variation of genome content within the species.genomics ͉ pathogenicity island ͉ evolution

Chemotaxis enhances the fitness of Salmonella enterica serotype Typhimurium (S. Typhimurium) during colitis. However, the chemotaxis receptors conferring this fitness advantage and their cognate signals generated during inflammation remain unknown. Here we identify respiratory electron acceptors that are generated in the intestinal lumen as by-products of the host inflammatory response as in vivo signals for methyl-accepting chemotaxis proteins (MCPs). Three MCPs, including Trg, Tsr and Aer, enhanced the fitness of S. Typhimurium in a mouse colitis model. Aer mediated chemotaxis towards electron acceptors (energy taxis) in vitro and required tetrathionate respiration to confer a fitness advantage in vivo. Tsr mediated energy taxis towards nitrate but not towards tetrathionate in vitro and required nitrate respiration to confer a fitness advantage in vivo. These data suggest that the energy taxis receptors Tsr and Aer respond to distinct in vivo signals to confer a fitness advantage upon S. Typhimurium during inflammation by enabling this facultative anaerobic pathogen to seek out favorable spatial niches containing host-derived electron acceptors that boost its luminal growth.

Background All soft and solid surface structures in the oral cavity are covered by the acquired pellicle followed by bacterial colonization. This applies for natural structures as well as for restorative or prosthetic materials; the adherent bacterial biofilm is associated among others with the development of caries, periodontal diseases, peri-implantitis, or denture-associated stomatitis. Accordingly, there is a considerable demand for novel materials and coatings that limit and modulate bacterial attachment and/or propagation of microorganisms. Objectives and findings The present paper depicts the current knowledge on the impact of different physicochemical surface characteristics on bioadsorption in the oral cavity. Furthermore, it was carved out which strategies were developed in dental research and general surface science to inhibit bacterial colonization and to delay biofilm formation by low-fouling or “easy-to-clean” surfaces. These include the modulation of physicochemical properties such as periodic topographies, roughness, surface free energy, or hardness. In recent years, a large emphasis was laid on micro- and nanostructured surfaces and on liquid repellent superhydrophic as well as superhydrophilic interfaces. Materials incorporating mobile or bound nanoparticles promoting bacteriostatic or bacteriotoxic properties were also used. Recently, chemically textured interfaces gained increasing interest and could represent promising solutions for innovative antibioadhesion interfaces. Due to the unique conditions in the oral cavity, mainly in vivo or in situ studies were considered in the review. Conclusion Despite many promising approaches for modulation of biofilm formation in the oral cavity, the ubiquitous phenomenon of bioadsorption and adhesion pellicle formation in the challenging oral milieu masks surface properties and therewith hampers low-fouling strategies. Clinical relevance Improved dental materials and surface coatings with easy-to-clean properties have the potential to improve oral health, but extensive and systematic research is required in this field to develop biocompatible and effective substances.

A hierarchical control of fimbrial gene expression limits laboratory grown cultures of Salmonella enterica serovar typhimurium (S. typhimurium) to the production of type I fimbriae encoded by the fimAICDHF operon. Here we show that an unlikely culprit, namely the 5 0 -untranslated region (5 0 -UTR) of a messenger (m)RNA, coordinated the regulation. Binding of CsrA to the 5 0 -UTR of the pefACDEF transcript was required for expression of plasmid-encoded fimbriae. The 5 0 -UTR of the fimAICDHF transcript cooperated with two small untranslated RNAs, termed CsrB and CsrC, in antagonizing the activity of the RNA binding protein CsrA. Through this post-transcriptional mechanism, the 5 0 -UTR of the fimAICDHF transcript prevented production of PefA, the major structural subunit of plasmidencoded fimbriae. This regulatory mechanism limits the costly expression of plasmid-encoded fimbriae to host environments in a mouse model. Collectively, our data suggest that the 5 0 -UTR of an mRNA coordinates a hierarchical control of fimbrial gene expression in S. typhimurium.

BackgroundThe MYC protein controls cellular functions such as differentiation, proliferation, and apoptosis. In response to genotoxic agents, cells overexpressing MYC undergo apoptosis. However, the MYC-regulated effectors acting upstream of the mitochondrial apoptotic pathway are still unknown.Principal FindingsIn this study, we demonstrate that expression of Myc is required to activate the Ataxia telangiectasia mutated (ATM)-dependent DNA damage checkpoint responses in rat cell lines exposed to ionizing radiation (IR) or the bacterial cytolethal distending toxin (CDT). Phosphorylation of the ATM kinase and its downstream effectors, such as histone H2AX, were impaired in the myc null cell line HO15.19, compared to the myc positive TGR-1 and HOmyc3 cells. Nuclear foci formation of the Nijmegen Breakage Syndrome (Nbs) 1 protein, essential for efficient ATM activation, was also reduced in absence of myc. Knock down of the endogenous levels of MYC by siRNA in the human cell line HCT116 resulted in decreased ATM and CHK2 phosphorylation in response to irradiation. Conversely, cell death induced by UV irradiation, known to activate the ATR-dependent checkpoint, was similar in all the cell lines, independently of the myc status.ConclusionThese data demonstrate that MYC contributes to the activation of the ATM-dependent checkpoint responses, leading to cell death in response to specific genotoxic stimuli.

Adhesins are crucial virulence factors of pathogenic bacteria involved in colonization, transmission and pathogenesis. Many bacterial genomes contain the information for a surprisingly large number of diverse adhesive structures. One prominent example is the invasive and facultative intracellular pathogen Salmonella enterica with an adhesiome of up to 20 adhesins. Such large repertoire of adhesins contributes to colonization of a broad range of host species and may allow adaptation to various environments within the host, as well as in non-host environments. For S. enterica, only few members of the adhesiome are functionally expressed under laboratory conditions, and accordingly the structural and functional understanding of the majority of adhesins is sparse. We have devised a simple and versatile approach to functionally express all adhesins of S. enterica serotype Typhimurium, either within Salmonella or within heterologous hosts such as Escherichia coli. We demonstrate the surface expression of various so far cryptic adhesins and show ultrastructural features using atomic force microscopy and transmission electron microscopy. In summary, we report for the first time the expression of the entire adhesiome of S. enterica serotype Typhimurium.

Delivery of microbial products into the mammalian cell cytosol by bacterial secretion systems is a strong stimulus for triggering pro-inflammatory host responses. Here we show that Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, tightly regulates expression of the invasion-associated type III secretion system (T3SS-1) and thus fails to activate these innate immune signaling pathways. The S. Typhi regulatory protein TviA rapidly repressed T3SS-1 expression, thereby preventing RAC1-dependent, RIP2-dependent activation of NF-κB in epithelial cells. Heterologous expression of TviA in S. enterica serovar Typhimurium (S. Typhimurium) suppressed T3SS-1-dependent inflammatory responses generated early after infection in animal models of gastroenteritis. These results suggest that S. Typhi reduces intestinal inflammation by limiting the induction of pathogen-induced processes through regulation of virulence gene expression.