scholarly journals TcsL Is an Essential Virulence Factor inClostridium sordelliiATCC 9714

2011 ◽  
Vol 79 (3) ◽  
pp. 1025-1032 ◽  
Author(s):  
Glen P. Carter ◽  
Milena M. Awad ◽  
Yibai Hao ◽  
Tennille Thelen ◽  
Ingrid L. Bergin ◽  
...  

ABSTRACTClostridium sordelliiis an important pathogen of humans and animals, causing a range of diseases, including myonecrosis, sepsis, and shock. Although relatively rare in humans, the incidence of disease is increasing, and it is associated with high mortality rates, approaching 70%. Currently, very little is known about the pathogenesis ofC. sordelliiinfections or disease. Previous work suggested that the lethal large clostridial glucosylating toxin TcsL is the major virulence factor, but a lack of genetic tools has hindered our ability to conclusively assign a role for TcsL or, indeed, any of the other putative virulence factors produced by this organism. In this study, we have developed methods for the introduction of plasmids intoC. sordelliiusing RP4-mediated conjugation fromEscherichia coliand have successfully used these techniques to insertionally inactivate thetcsLgene in the reference strain ATCC 9714, using targetron technology. Virulence testing revealed that the production of TcsL is essential for the development of lethal infections byC. sordelliiATCC 9714 and also contributes significantly to edema seen during uterine infection. This study represents the first definitive identification of a virulence factor inC. sordelliiand opens the way for in-depth studies of this important human pathogen at the molecular level.

2005 ◽  
Vol 71 (11) ◽  
pp. 7224-7228 ◽  
Author(s):  
Tina Lütke-Eversloh ◽  
Gregory Stephanopoulos

ABSTRACT In order to get insights into the feedback regulation by tyrosine of the Escherichia coli chorismate mutase/prephenate dehydrogenase (CM/PDH), which is encoded by the tyrA gene, feedback-inhibition-resistant (fbr) mutants were generated by error-prone PCR. The tyrA fbr mutants were selected by virtue of their resistance toward m-fluoro-d,l-tyrosine, and seven representatives were characterized on the biochemical as well as on the molecular level. The PDH activities of the purified His6-tagged TyrA proteins exhibited up to 35% of the enzyme activity of TyrAWT, but tyrosine did not inhibit the mutant PDH activities. On the other hand, CM activities of the TyrAfbr mutants were similar to those of the TyrAWT protein. Analyses of the DNA sequences of the tyrA genes revealed that tyrA fbr contained amino acid substitutions either at Tyr263 or at residues 354 to 357, indicating that these two sites are involved in the feedback inhibition by tyrosine.


2018 ◽  
Vol 6 (11) ◽  
pp. 2023-2029 ◽  
Author(s):  
Sayed Yousef Mojtahedi ◽  
Aliakbar Rahbarimanesh ◽  
Leila Khedmat ◽  
Anahita Izadi

AIM: The objective of this study was to evaluate the frequency of risk factors for bacteremia in children less than 15 years of age was determined in Bahrami Hospital during 2013-2016. METHODS: This study conducted on 84 children aged 3 months’ to15 years old, who hospitalised in the pediatrics ward and the PICU in Bahrami Hospital from 2012 to 2016. Our study consisted of 46 boys (54.2%) and 38 girls. Moreover, 24.1% of subjects (20 patients) were entered in the study as young as three months old, followed by three months to three years (49.4 %; 41 subjects), and 3 to 15 years of age (26.5%; 22 individuals). RESULTS: The average hospitalization duration was determined to be 15.30 ± 8.75 days. Moreover, our results revealed that a history of blood transfusion in 11.2% of patients. On the other hand, 35.7% of cases were determined to be positive for blood cultures. The microorganisms reported from positive blood cultures include Enterobacter (81.48%), Escherichia coli (11.11%) and Klebsiella (3.70%). Also, 50% of patients were hospitalised in the internal ward, 12% received immunosuppressive drugs, and 96.4% of the patients had a history of vaccination. CONCLUSION: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.


Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 98 ◽  
Author(s):  
Òscar Gulías ◽  
Giselle McKenzie ◽  
Miquel Bayó ◽  
Montserrat Agut ◽  
Santi Nonell

The emergence of multidrug-resistant bacteria is a growing problem and alternative therapies are being sought to effectively address this issue. The aim of this study is to assess a range of Escherichia coli strains’ susceptibility to Methylene Blue-mediated antimicrobial photodynamic therapy and determine if this is affected by their antibiotic-resistance profile. Two reference and twenty-four uropathogenic clinical E. coli strains were used in this study. All were tested in vitro for antimicrobial susceptibility against sixteen antibiotics. Strains underwent photodynamic treatments using the photosensitizer Methylene Blue with red light and tested in both planktonic and biofilm state. It was found that reference strain ATCC 25922 was susceptible to all tested antibiotics whereas reference strain ATCC 35218 showed resistance only to Ampicillin. With the exception of strains number 16 and 22, all of the isolated strains were multidrug-resistant according to the criteria established by the European Centre for Disease Prevention and Control and the Centre for Disease Control and Prevention, where acquired non-susceptibility to at least one agent in three or more antimicrobial categories is outlined. Photodynamic therapy induced more than 3 log10 colony-forming units’ reduction to all strains in planktonic state. Whereas when tested in biofilm state, two and a half times the original dose of methylene blue was necessary to cause a 3 log10 antimicrobial effect. There were statistically significant differences in susceptibility among the strains tested in both the planktonic and biofilm experiments. Nevertheless, antimicrobial photodynamic therapy could inactivate all multidrug-resistant strains in the planktonic and biofilm state.


2015 ◽  
Vol 59 (11) ◽  
pp. 7054-7060 ◽  
Author(s):  
Jing Dong ◽  
Yong Zhang ◽  
Yutao Chen ◽  
Xiaodi Niu ◽  
Yu Zhang ◽  
...  

ABSTRACTShiga-like toxins (Stxs), produced by pathogenicEscherichia coli, are a major virulence factor involved in severe diseases in human and animals. These toxins are ribosome-inactivating proteins, and treatment for diseases caused by them is not available. Therefore, there is an urgent need for agents capable of effectively targeting this lethal toxin. In this study, we identified baicalin, a flavonoid compound used in Chinese traditional medicine, as a compound against Shiga-like toxin 2 (Stx2). We found that baicalin significantly improves renal function and reduces Stx2-induced lethality in mice. Further experiments revealed that baicalin induces the formation of oligomers by the toxin by direct binding. We also identified the residues important for such interactions and analyzed their roles in binding baicalin by biophysical and biochemical analyses. Our results establish baicalin as a candidate compound for the development of therapeutics against diseases caused by Stxs.


1999 ◽  
Vol 67 (6) ◽  
pp. 2776-2782 ◽  
Author(s):  
Adrian M. Whatmore ◽  
Samantha J. King ◽  
Neil C. Doherty ◽  
Daniel Sturgeon ◽  
Neil Chanter ◽  
...  

ABSTRACT Although often considered a strict human pathogen,Streptococcus pneumoniae has been reported to infect and cause pneumonia in horses, although the pathology appears restricted compared to that of human infections. Here we report on the molecular characterization of a group of S. pneumoniae isolates obtained from horses in England and Ireland. Despite being obtained from geographically distinct locations, the isolates were found to represent a tight clonal group, virtually identical to each other but genetically distinguishable from more than 120 divergent isolates of human S. pneumoniae. A comprehensive analysis of known pneumococcal virulence determinants was undertaken in an attempt to understand the pathogenicity of equine pneumococci. Surprisingly, equine isolates appear to lack activities associated with both the hemolytic cytotoxin pneumolysin, often considered a major virulence factor of pneumococci, and the major autolysin gene lytA, also considered an important virulence factor. In support of phenotypic data, molecular studies demonstrated a deletion of parts of the coding sequences of both lytA and ply genes in equine pneumococci. The implications of these findings for the evolution and pathogenicity of equine S. pneumoniae are discussed.


Author(s):  
Manfred E. Bayer

The first step in the infection of a bacterium by a virus consists of a collision between cell and bacteriophage. The presence of virus-specific receptors on the cell surface will trigger a number of events leading eventually to release of the phage nucleic acid. The execution of the various "steps" in the infection process varies from one virus-type to the other, depending on the anatomy of the virus. Small viruses like ØX 174 and MS2 adsorb directly with their capsid to the bacterial receptors, while other phages possess attachment organelles of varying complexity. In bacteriophages T3 (Fig. 1) and T7 the small conical processes of their heads point toward the adsorption site; a welldefined baseplate is attached to the head of P22; heads without baseplates are not infective.


Author(s):  
A.J. Verkleij

Freeze-fracturing splits membranes into two helves, thus allowing an examination of the membrane interior. The 5-10 rm particles visible on both monolayers are widely assumed to be proteinaceous in nature. Most membranes do not reveal impressions complementary to particles on the opposite fracture face, if the membranes are fractured under conditions without etching. Even if it is considered that shadowing, contamination or fracturing itself might obscure complementary pits', there is no satisfactory explanation why under similar physical circimstances matching halves of other membranes can be visualized. A prominent example of uncomplementarity is found in the erythrocyte manbrane. It is wall established that band 3 protein and possibly glycophorin represents these nonccmplanentary particles. On the other hand a number of membrane types show pits opposite the particles. Scme well known examples are the ";gap junction',"; tight junction, the luminal membrane of the bladder epithelial cells and the outer membrane of Escherichia coli.


Mathematics ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 600 ◽  
Author(s):  
Marco Montalva-Medel ◽  
Thomas Ledger ◽  
Gonzalo A. Ruz ◽  
Eric Goles

In Veliz-Cuba and Stigler 2011, Boolean models were proposed for the lac operon in Escherichia coli capable of reproducing the operon being OFF, ON and bistable for three (low, medium and high) and two (low and high) parameters, representing the concentration ranges of lactose and glucose, respectively. Of these 6 possible combinations of parameters, 5 produce results that match with the biological experiments of Ozbudak et al., 2004. In the remaining one, the models predict the operon being OFF while biological experiments show a bistable behavior. In this paper, we first explore the robustness of two such models in the sense of how much its attractors change against any deterministic update schedule. We prove mathematically that, in cases where there is no bistability, all the dynamics in both models lack limit cycles while, when bistability appears, one model presents 30% of its dynamics with limit cycles while the other only 23%. Secondly, we propose two alternative improvements consisting of biologically supported modifications; one in which both models match with Ozbudak et al., 2004 in all 6 combinations of parameters and, the other one, where we increase the number of parameters to 9, matching in all these cases with the biological experiments of Ozbudak et al., 2004.


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