Guldbrandsenerlandsen8055

gallisepticum Vaccination appears to protect the structural and functional integrity of the tracheal mucosa 2 weeks after infection with M. gallisepticum. Copyright © 2020 American Society for Microbiology.Legionella pneumophila, the etiological agent of Legionnaires' Disease, employs an arsenal of hundreds of Dot/Icm-translocated effector proteins to facilitate replication within eukaryotic phagocytes. Several effectors, called metaeffectors, function to regulate the activity of other Dot/Icm-translocated effectors during infection. The metaeffector Lpg2505 is essential for L. pneumophila intracellular replication only when its cognate effector, SidI, is present. SidI is a cytotoxic effector that interacts with the host translation factor eEF1A and potently inhibits eukaryotic protein translation by an unknown mechanism. Here, we evaluated the impact of Lpg2505 on SidI-mediated phenotypes and investigated the mechanism of SidI function. We determined that Lpg2505 binds with nanomolar affinity to SidI and suppresses SidI-mediated inhibition of protein translation. SidI binding to eEF1A and Lpg2505 is not mutually exclusive and these proteins bind distinct regions of SidI. We also discovered that SidI possesses GDP-dependent glycosyl hydrolase activity and that this activity is regulated by Lpg2505. We have therefore renamed Lpg2505, MesI (Metaeffector of SidI). This work reveals novel enzymatic activity for SidI and provides insight into how intracellular replication of L. pneumophila is regulated by a metaeffector. Copyright © 2020 American Society for Microbiology.In high-income countries, the leading causes of death are non-communicable diseases (NCD), such as obesity, cancer and cardiovascular disease. An important feature of most NCDs is inflammation-induced gut dysbiosis characterized by a shift in the microbial community structure from obligate to facultative anaerobes such as Proteobacteria. This microbial imbalance can contribute to disease pathogenesis by either a depletion in or the production of microbiota derived metabolites. However, little is known about the mechanism by which inflammation mediated changes in host physiology disrupt the microbial ecosystem in our large intestine leading to disease. Recent work by our group suggests that during gut homeostasis, epithelial hypoxia derived from PPARγ-dependent β-oxidation of microbiota-derived short-chain fatty acids limits oxygen availability in the colon, thereby maintaining a balanced microbial community. During inflammation, disruption in gut anaerobiosis drives an expansion of facultative anaerobic Enterobacteriaceae, regardless of their pathogenic potential. Therefore, our research group is currently exploring the concept that dysbiosis-associated expansion of Enterobacteriaceae can be viewed as a microbial signature of epithelial dysfunction and may play a greater role in different models of NCDs, including diet-induced obesity, atherosclerosis and inflammation-associated colorectal cancer. Copyright © 2020 American Society for Microbiology.Bovine Digital Dermatitis (BDD), an infectious disease of the bovine foot with a predominant treponemal aetiology, is a leading cause of lameness in dairy and beef herds worldwide. BDD is poorly responsive to antimicrobial therapy and exhibits a relapsing clinical course; an effective vaccine is therefore urgently sought. Using a 'reverse vaccinology' approach, the present study surveyed the genomes of the three BDD-associated Treponema phylogroups for putative β-barrel outer membrane proteins and considered their potential as vaccine candidates. Selection criteria included the presence of a signal peptidase I cleavage site, a predicted β-barrel fold and cross-phylogroup homology. Four candidate genes were overexpressed in Escherichia coli BL21 (DE3), refolded and purified. Consistent with their classification as β-barrel OMPs, circular dichroism spectroscopy revealed the adoption of a predominantly β-sheet secondary structure. These recombinant proteins, when screened for their ability to adhere to immobilised ECM components, exhibited a diverse range of ligand specificities. All four proteins specifically and dose-dependently adhered to bovine fibrinogen. One recombinant protein was identified as a candidate diagnostic antigen (disease specificity, 75%). Finally, when adjuvanted with aluminium hydroxide and administered to BDD-naïve calves using a prime-boost vaccination protocol, these proteins were immunogenic, eliciting specific IgG antibodies. In summary, we present the description of four putative treponemal β-barrel OMPs that exhibit the characteristics of multispecific adhesins. The observed interactions with fibrinogen may be critical to host colonisation and dissemination and it is hypothesised that vaccination-induced antibody blockade of these interactions will impede treponemal virulence and thus be of therapeutic value. selleck kinase inhibitor Copyright © 2020 Staton et al.Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacterium that infects the human gastrointestinal tract, causing a wide range of disorders that vary in severity from mild diarrhea to toxic megacolon and/or death. Over the past decade, incidence, severity, and costs associated with C. difficile infection (CDI) have increased dramatically in both the pediatric and adult populations. The factors driving this rapidly evolving epidemiology remain largely unknown but are likely due in part to previously unappreciated host, microbiota, and environmental factors. In this review, we will cover the risks and challenges of CDI in adult and pediatric populations and examine asymptomatic colonization in infants. We will also discuss the emerging role for diet, pharmaceutical drugs, and pathogen-microbiota interactions in C. difficile pathogenesis, and discuss the impact of host-microbiota interactions in the manifestation of C. difficile-associated disease. Finally, we highlight new areas of research and novel strategies that may shed light on this complex infection and provide insights into the future of microbiota-based therapeutics for CDI. Copyright © 2020 American Society for Microbiology.