Differential Effects of "Resurrecting" Csp Pseudoproteases during Clostridioides difficile Spore Germination.

Differential Effects of "Resurrecting" Csp Pseudoproteases during Clostridioides difficile Spore Germination. Biochem J. 2020 Apr 03;: Authors: Donnelly ML, Forster ER, Rohlfing AE, Shen A Abstract Clostridioides difficileis a spore-forming bacterial pathogen that is the leading cause of hospital-acquired gastroenteritis. C. difficileinfections begin when its spore form germinates in the gut upon sensing bile acids. These germinants induce a proteolytic signaling cascade controlled by three members of the subtilisin-like serine protease family, CspA, CspB, and CspC. Notably, even though CspC and CspA are both pseudoproteases, they are nevertheless required to sense germinants and activate the protease, CspB. Thus, CspC and CspA are part of a growing list of pseudoenzymes that play important roles in regulating cellular processes. However, despite their importance, the structural properties of pseudoenzymes that allow them to function as regulators remain poorly understood. Our recently solved crystal structure of CspC revealed that its pseudoactive site residues align closely with the catalytic triad of CspB, suggesting that it might be possible to "resurrect" the ancestral protease activity of the CspC and CspA pseudoproteases. Here, we demonstrate that restoring the catalytic triad to these pseudoproteases fails to resurrect their protease activity. We further show that the pseudoactive site substitutions differentially affect the s...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research

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Clostridium difficile infection (CDI) has an increasing pediatric prevalence worldwide. However, molecular characteristics of C. difficile in Chinese children with acute gastroenteritis have not been reported.
Source: BMC Infectious Diseases - Category: Infectious Diseases Authors: Tags: Research article Source Type: research
AbstractIn acute gastroenteritis (AGE), identification of the infectious agent is important for patient management. Since symptoms do not reliably identify the agent, microbiological diagnostics are important. Conventional methods lack sensitivity and often take days. Multiplex PCR panels offer fast and sensitive alternatives. Our aim was to assess the performance of the new QIAstat Gastrointestinal Panel (GIP) detecting 24 different gastroenteric pathogens from stool in Cary-Blair transport medium (Adenovirus F 40/41, Astrovirus, Norovirus GI/GII, Rotavirus A, Sapovirus,Campylobacter spp.,Clostridium difficile,Plesiomonas...
Source: European Journal of Clinical Microbiology and Infectious Diseases - Category: Microbiology Source Type: research
Clostridioides (Clostridium) difficile infection (CDI) is the most common causative pathogen of health care-associated gastrointestinal infections; however, due to the overlap of clinical symptoms with those of other causes of acute gastroenteritis, the selection of the most appropriate laboratory test is difficult. From April to October 2018, 640 stool samples requested for CDI testing were examined using the mariPOC CDI and Gastro test (ArcDia), which allows the detection of C. difficile glutamate dehydrogenase (GDH) and toxin A/B, norovirus genogroups GI and GII.4, rotavirus, adenovirus, and Campylobacter spp. In parall...
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Immunoassays Source Type: research
In conclusion, the large diversity of agent combinations and disease situations detected in neonatal diarrhea outbreaks of this study stand for a more personalized diagnosis and management advice at a farm level.
Source: Veterinary Microbiology - Category: Veterinary Research Source Type: research
CONCLUSIONS: Current literature show similar risks for bacterial pathogens. Studies are limited for viral and parasitic pathogens. The evaluated risk-factors for PI-IBS varied among the included studies and the existing evidence is insufficient to identify pathogen-specific risk factors. PMID: 31112663 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
This study provides new insight into the characterization of foodborne C. perfringens and highlights the potential of WGS for the investigation of FBOs. Introduction Clostridium perfringens is a Gram-positive, spore-forming, anaerobic, rod-shaped bacterium, known as an important causative agent of foodborne and non-foodborne gastroenteritis (Grass et al., 2013). The ability of this bacterium to form resistant spores contributes to its survival in many environmental niches, including soil, sewage, foods, and the intestinal microbiota of humans and animals (Xiao, 2014; Li et al., 2016). C. perfringens can cause necro...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Conclusion: In our experience using the PCR- Biofire assay we show that this approach is feasible and can be used safely to tailor therapy in immunocompromised patients. In all cases, E.Coli was found, most frequently STEC (Shiga-like toxin producing E. coli). Using this approach enable us to identify new pathogens causing diarrhea in immunocompromised patients, extremely quickly. These preliminary results reveal the need for more clinical experience using the Biofire FilmArray as a diagnostic test for patients with MM and other haematological malignancies, who present acutely with severe diarrhea.DisclosuresTadmor: NOVART...
Source: Blood - Category: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections Source Type: research
We examined epidemiologic features of all health care–associated outbreak investigations at an academic hospital during a 5-year period.MethodsHealth care–associated outbreak investigations at an academic hospital (2012-2016) were retrospectively reviewed through data on comprehensive hospital-wide surveillance and pulsed-field gel electrophoresis (PFGE) analysis.ResultsFifty-one health care–associated outbreaks (annual range, 8-15), including 26 (51%) outbreaks in intensive care units (ICUs), and 263 infected-colonized patients involved in these outbreaks were identified. The frequency of pathogens varie...
Source: American Journal of Infection Control - Category: Infectious Diseases Source Type: research
Conclusions This study demonstrated epidemiologic characteristics of multiple outbreaks between ICUs and non-ICUs and the value of molecular typing in understanding the epidemiology of health care–associated outbreaks.
Source: American Journal of Infection Control - Category: Infectious Diseases Source Type: research
The FilmArray GI panel (BioFire Diagnostics, Salt Lake City, UT) is a multiplex, on-demand, sample-to-answer, real-time PCR assay for the syndromic diagnosis of infectious gastroenteritis that has become widely adopted and, in some instances, has replaced conventional stool culture and parasite exams. Conventional testing has historically been restricted among hospitalized patients due to low diagnostic yield, but it is not known whether use of the FilmArray GI panel should be circumscribed. Cary-Blair stool samples submitted for FilmArray GI panel in adult patients admitted to an academic hospital from August 2015 to Janu...
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Bacteriology Source Type: research
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