Current developments in lantibiotic discovery for treating Clostridium difficile infection

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

Related Links:

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
Authors: Mateu L, Fernández-Rivas G, Sopena N Abstract Clostridioides difficile is the main cause of healthcare-associated diarrhoea in adults. The incidence of C.difficile infection (CDI) has increased in recent years. The risk of recurrence of CDI is 15%-25% in a first episode and this risk is increased in subsequent episodes. Toxigenic culture and cytotoxicity tests are the reference techniques for the microbiological diagnosis of CDI. These are laborious and slow techniques and therefore they have been replaced in clinical practice by the application of a multi-step algorithm that includes the detection ...
Source: Medicina Clinica - Category: General Medicine Tags: Med Clin (Barc) Source Type: research
Clostridioides difficile infection (CDI) is associated with increasing morbidity and mortality posing an urgent threat to public health. Recurrence of CDI after successful treatment with antibiotics is high, thus necessitating discovery of novel therapeutics against this enteric pathogen. Administration of the secondary bile acid ursodeoxycholic acid (UDCA; ursodiol) inhibits the life cycles of various strains of C. difficile in vitro, suggesting that the FDA-approved formulation of UDCA, known as ursodiol, may be able to restore colonization resistance against C. difficile in vivo. However, the mechanism(s) by which ursod...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Bacterial Infections Source Type: research
This study explores the effect of age on cellular and cytokine immune responses during C. difficile infection. Young mice (2 to 3 months old) and aged mice (22 to 28 months old) were rendered susceptible to C. difficile infection with the antibiotic cefoperazone and then infected with C. difficile strains with varied disease-causing potentials. We observe that the host age and the infecting C. difficile strain influenced the severity of disease associated with infection. Tissue-specific CD45+ immune cell responses occurred at the time of peak disease severity in the ceca and colons of all mice infected with a high-virulenc...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Host Response and Inflammation Source Type: research
More News: Clostridium Difficile | Drugs & Pharmacology