The Novel DNA Binding Mechanism of Ridinilazole, a Precision Antibiotic.

Clostridioides difficile infection (CDI) causes substantial morbidity and mortality worldwide with limited antibiotic treatment options. Ridinilazole is a precision bisbenzimidazole antibiotic being developed to treat CDI and reduce unacceptably high rates of infection recurrence in patients. Although in late clinical development, the precise mechanism of action by which ridinilazole elicits its bactericidal activity has remained elusive.

Moraxella-dominated pediatric nasopharyngeal microbiota associate with upper respiratory infection and sinusitis.

Background: Distinct bacterial upper airway microbiota structures have been described in pediatric populations, and relate to risk of respiratory viral infection and, exacerbations of asthma. We hypothesized that distinct nasopharyngeal (NP) microbiota structures exist in pediatric populations, relate to environmental exposures and modify risk of acute sinusitis or upper respiratory infection (URI) in children.

Methods: Bacterial 16S rRNA profiles from nasopharyngeal swabs (n = 354) collected longitudinally over a one-year period from 58 children, aged four to seven years, were analyzed and correlated with environmental variables, URI, and sinusitis outcomes.

High-density transposon libraries utilising outward-oriented promoters identify mechanisms of action and resistance to antimicrobials.

The use of bacterial transposon mutant libraries in phenotypic screens is a well-established technique for determining which genes are essential or advantageous for growth in conditions of interest. Standard, inactivating, transposon libraries cannot give direct information about genes whose over-expression gives a selective advantage. We report the development of a system wherein outward-oriented promoters are included in mini-transposons, generation of transposon mutant libraries in Escherichia coli and Pseudomonas aeruginosa and their use to probe genes important for growth under selection with the antimicrobial fosfomycin, and a recently-developed leucyl-tRNA synthase inhibitor.

A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis.

Microbial dysbiosis commonly occurs in patients with inflammatory bowel diseases (IBD). Exogenous causes of dysbiosis such as antibiotics and diet are well described, but host derived causes are understudied. A20 is a potent regulator of signals triggered by microbial pattern molecules, and A20 regulates susceptibility to intestinal inflammation in mice and in humans.

Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity.

The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites.

Nasopharyngeal microbiota composition of children is related to the frequency of upper respiratory infection and acute sinusitis.

Background: Upper respiratory infections (URI) and their complications are a major healthcare burden for pediatric populations. Although the microbiology of the nasopharynx is an important determinant of the complications of URI, little is known of the nasopharyngeal (NP) microbiota of children, the factors that affect its composition, and its precise relationship with URI.

Results: Healthy children (n = 47) aged 49-84 months from a prospective cohort study based in Wisconsin, USA, were examined.

Amelioration of DSS-induced murine colitis by VSL#3 supplementation is primarily associated with changes in ileal microbiota composition.

Inflammatory bowel diseases encompass gastrointestinal illnesses typified by chronic inflammation, loss of epithelial integrity and gastrointestinal microbiota dysbiosis. In an effort to counteract these characteristic perturbations, we used stem cells and/or a probiotic therapy in a murine model of Dextran Sodium Sulfate induced colitis to examine both their efficacy in ameliorating disease and impact on niche-specific microbial communities of the lower GI tract. Colitis was induced in C57BL/6 mice by administering 3% DSS in drinking water for 10 days prior to administering one of three treatment plans: daily probiotic (VSL#3) supplementation for 3 days, a single tail vein injection of 1x10 (6) murine mesenchymal stem cells, or both.

The effects of intestinal microbial community structure on disease manifestation in IL-10-/- mice infected with Helicobacter hepaticus.

Background: The aberrant inflammation that is the hallmark of the inflammatory bowel diseases (IBD) is associated with several factors, including changes in the intestinal microbiota. Here, we confirmed that an intestinal microbiota is needed for development of typhlocolitis in Helicobacter hepaticus infected IL-10-/- C57BL/6 mice, and investigated the role of the microbiota in modulating disease.

Results: We altered the murine microbiota by treatment with the antibiotics vancomycin or cefoperazone prior to H.

Probiotic strategies for treatment of respiratory diseases.

Recent advances in next-generation sequencing and phylogenetic microarray technologies have identified diverse, niche-specific microbial communities that comprise the human superorganism. Mucosal microbiome perturbation is a prominent feature of an increasing number of chronic inflammatory disorders, including respiratory diseases, and efforts are now focused on identifying novel microbe-based strategies to treat or manage these conditions. Considering the evidence for niche-specificity and the diversity of function that human microbial communities afford, the range of therapeutic species used to date in probiotic supplements is strikingly narrow and is limited to species typically of gastrointestinal origin.

Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis.

Persistent mucosal inflammation and microbial infection are characteristics of chronic rhinosinusitis (CRS). Mucosal microbiota dysbiosis is found in other chronic inflammatory diseases; however, the relationship between sinus microbiota composition and CRS is unknown. Using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, we demonstrate that the sinus microbiota of CRS patients exhibits significantly reduced bacterial diversity compared with that of healthy controls.

Role of the microbiota in inflammatory bowel diseases.

Studying the role of the human microbiome as it relates to human health status has revolutionized our view of microbial community contributions to a large number of diseases, particularly chronic inflammatory disorders. The lower gastrointestinal (GI) tract houses trillions of microbial cells representing a large diversity of species in relatively well-defined phylogenetic ratios that are associated with maintenance of key aspects of host physiology and immune homeostasis. It is not surprising, therefore, that many GI inflammatory diseases, including inflammatory bowel disease (IBD), are associated with substantial changes in the composition of these microbial assemblages, either as a cause or consequence of host inflammatory response.

Microbial ecology of the murine gut associated with the development of dextran sodium sulfate-induced colitis.

Background: Dextran sodium sulfate (DSS) is used to induce murine colitis. Although the exact mechanism by which DSS administration causes disease is unknown, evidence suggests that the resident bacteria play a role in the development of murine DSS colitis, analogous to their role in human inflammatory bowel diseases.

Methods: C57BL/6 mice received 5% DSS in the drinking water and were euthanized 3 days and 14 days after the initiation of DSS treatment.

A cross-sectional study of isolates from sputum samples from bacterial pneumonia patients in Trinidad.

We determined the frequency of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Gram-negative enteric bacteria (GNEB) in pneumonia patients, determined the antibiograms of these pathogens, and investigated the relationship between pneumonia and selected risk factors. Sputum and demographic data were collected from 124 pneumonia patients. Sputum was cultured for S.