Current developments in lantibiotic discovery for treating Clostridium difficile infection

Source: Expert Opinion on Drug Discovery - Category: Drugs & Pharmacology Authors: Source Type: research

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AbstractDespite improvements in hospital infection prevention and control, healthcare associated infections (HAIs) remain a challenge with significant patient morbidity, mortality, and cost for the healthcare system. In this review, we use a One Health framework (human, animal, and environmental health) to explain the epidemiology, demonstrate key knowledge gaps in infection prevention policy, and explore improvements to control Gram-positive pathogens in the healthcare environment. We discuss patient and healthcare worker interactions with the hospital environment that can lead to transmission of the most common Gram-posi...
Source: Antimicrobial Resistance and Infection Control - Category: Infectious Diseases Source Type: research
Publication date: Available online 30 May 2020Source: American Journal of Infection ControlAuthor(s): Hiroki Kitagawa, Minako Mori, Toshinori Hara, Seiya Kashiyama, Norifumi Shigemoto, Hiroki Ohge
Source: American Journal of Infection Control - Category: Infectious Diseases Source Type: research
Abstract The yeast Saccharomyces boulardii CNCM I-745 is a unique, non-bacterial microorganism classified as a probiotic agent. In this review article, at first, we briefly summarized the mechanisms responsible for its probiotic properties, e.g. adhesion to and elimination of enteropathogenic microorganisms and their toxins; extracellular cleavage of pathogens' virulent factors; trophic and anti-inflammatory effects on the intestinal mucosa. The efficacy of S. boulardii administration was tested in variety of human diseases. We discussed the results of S. boulardii CNCM I-745 use in the treatment or prevention of ...
Source: Current Microbiology - Category: Microbiology Authors: Tags: Curr Microbiol Source Type: research
AbstractPurpose of ReviewSyndromic gastrointestinal (GI) panels are molecular tests that evaluate stool specimens for multiple enteric pathogens simultaneously, including viruses, bacteria, and parasites. The Luminex xTAG GI panel includes 14 microbial targets and the Biofire FilmArray GI panel includes 22. The purpose of this scoping review was to describe clinical use of these two commercially available syndromic GI panels.Recent FindingsCompared with conventional testing, syndromic panels increase the number of potential pathogens identified by two- to fivefold. Syndromic panels were associated with non-reproducible res...
Source: Current Infectious Disease Reports - Category: Infectious Diseases Source Type: research
CotE is a coat protein that is present in the spores of Clostridium difficile, an obligate anaerobic bacterium and a pathogen that is a leading cause of antibiotic-associated diarrhoea in hospital patients. Spores serve as the agents of disease transmission, and CotE has been implicated in their attachment to the gut epithelium and subsequent colonization of the host. CotE consists of an N-terminal peroxiredoxin domain and a C-terminal chitinase domain. Here, a C-terminal fragment of CotE comprising residues 349 – 712 has been crystallized and its structure has been determined to reveal a core eight-stranded β -...
Source: Acta Crystallographica Section F - Category: Biochemistry Authors: Tags: Clostridium difficile spores CotE glycosyl hydrolase 3D domain swapping research communications Source Type: research
AbstractPurposeExisting clinical or microbiological scores are not sensitive enough to obtain prompt identification of patients at risk of complicatedClostridium difficile infection (CDI). Our aim was to use a CDI animal model to evaluate 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET) as a marker of severe course of infection.ProceduresCDI was induced with cefoperazone for 10  days followed by clindamycin 1 day beforeC. difficile inoculation. Mice were divided into wild type (n = 6), antibiotic without infection (ACn = 4), h001-infected (n = 5...
Source: Molecular Imaging and Biology - Category: Molecular Biology Source Type: research
Currently available diagnostic tests for Clostridioides difficile infection (CDI) lack specificity or sensitivity, which has led to guideline recommendations for multistep testing algorithms. Ultrasensitive assays for detection of C. difficile toxins provide measurements of disease-specific markers at very low concentrations. These assays may show improved accuracy compared to that of current testing methods and offer a potential standalone solution for CDI diagnosis, although large studies of clinical performance and accuracy are lacking.
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Minireviews Source Type: research
Abstract Chromosomal resistance to metronidazole has emerged in clinical Clostridioides difficile, but the genetic mechanisms remain unclear. This is further hindered by the inability to generate spontaneous metronidazole-resistant mutants in the lab to interpret genetic variations in clinical isolates. We therefore constructed a mismatch repair mutator, in non-toxigenic ATCC 700057, to survey the mutational landscape for de novo resistance mechanisms. In separate experimental evolutions, the mutator adopted a deterministic path to resistance, with truncation of ferrous iron transporter FeoB1 as a first-step mecha...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
AbstractBackgroundThe global epidemic of nosocomial diarrhea caused byClostridioides (Clostridium) difficile started in 2000, with high mortality rates and emergence of a new hypervirulent strain NAP1/BI/027. The aim of this study was to assess the presence of ribotype 027 and otherC. difficile ribotypes in a Serbian University Hospital, compare the temporal variability of ribotypes 3  years apart, as well as to compare clinical, demographic and laboratory characteristics and disease outcome among patients infected with 027 and non-027 ribotype. This was a prospective observational cohort study addressing 4-month inte...
Source: Gut Pathogens - Category: Microbiology Source Type: research
The study by Miranda-Katz et al from Kaiser Permanente Northern California approximates the true incidence of community-associated Clostridioides difficile diarrheal disease —13.7 cases per 100 000 per year for the population aged 1 to 17 years.
Source: The Journal of Pediatrics - Category: Pediatrics Authors: Tags: The Editors' Perspectives Source Type: research
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