Clostridium perfringens extracellular toxins and enzymes: 20 and counting

2015 ◽  
Vol 36 (3) ◽  
pp. 114 ◽  
Author(s):  
Sarah A Revitt-Mills ◽  
Julian I Rood ◽  
Vicki Adams

Clostridium perfringens is a Gram-positive, anaerobic bacterium that is widely distributed in the environment; it is found in soil and commonly inhabits the gastrointestinal tract of humans and animals1,2. The ubiquitous nature of this bacterium has resulted in it becoming a major cause of histotoxic and enteric diseases3. The success of C. perfringens as both a pathogen and a commensal bacterium lies in its ability to produce a large number of potent toxins and extracellular enzymes4. This diverse toxin repertoire results in a broad range of diseases including gas gangrene, various enterotoxaemias, food poisoning and necrotic enteritis4–6. Since 2007, six new toxins have been identified, adding to the ever-increasing range of potential C. perfringens virulence determinants. This paper briefly reviews the plethora of toxins and extracellular enzymes produced by C. perfringens, highlighting their importance in disease and strain classification as well as introducing the latest additions to the ever increasing C. perfringens toxin family.

2019 ◽  
Vol 75 (01) ◽  
pp. 6161-2019
Author(s):  
NINA KOZIEŁ ◽  
ELŻBIETA KUKIER ◽  
KRZYSZTOF KWIATEK

Clostridium perfringens is one of the most widespread anaerobic spore forming bacteria found in the environment. The toxotype A of the species inhabits the gastrointestinal tract of birds and mammals exhibiting pathogenic properties in the immunocompromised host. The virulence determinants of C. perfringens are toxins and extracellular enzymes which cause gas gangrene, enteritis necroticans, food poisoning, and non-food borne gastrointestinal infections in humans. The young animals suffer from enterotoxaemia, dysentery and necrotic enteritis due to the anaerobic spore forming bacilli. This article reviews the epidemiological significance of C. perfringens and its disease diagnostics, taking into account all known to date virulence determinants of the microorganism.


1968 ◽  
Vol 14 (6) ◽  
pp. 705-709 ◽  
Author(s):  
A. H. W. Hauschild ◽  
F. S. Thatcher

Classical and food-poisoning strains of Clostridium perfringens type A were tested for their capacity to produce gas gangrene in guinea pigs.The virulence of food-poisoning strains producing heat-sensitive spores and showing beta hemolysis on sheep-blood agar was comparable to that of the classical strains. The most virulent strains of both groups produced fatal infection with only three to five vegetative cells. Of 13 food-poisoning, heat-sensitive strains showing no beta hemolysis, only three were lethal when a minimum of 4 × 104 to 4 × 108 cells was injected. None of the food-poisoning, heat-resistant strains produced fatal infection with cell numbers up to 4 × 108. The groups of strains showed a correlation between virulence and formation of alpha toxin in liquid culture.It is concluded that a number of heat-sensitive, beta-hemolytic strains of C. perfringens may cause gas gangrene as well as food poisoning, and that the current subdivision of C. perfringens type A strains into classical and food-poisoning groups is no longer tenable.


2019 ◽  
Vol 9 (1-2) ◽  
pp. 127-133
Author(s):  
Luke R. Cypher ◽  
Christopher Sullivan ◽  
Ryan Jones ◽  
Angelina Phillips

Acute intravascular hemolysis is a rare and often lethal complication of Clostridium perfringens septicemia.Clostridium perfringens is an anaerobic, gram-positive spore-forming rod which is commonly implicated in cases of food poisoning, gas gangrene, and severe hemolytic anemia in humans via the alpha-toxin (phospholipase C). We report an interesting and rare case of a 72-year-old woman who developed massive intravascular hemolysis secondary to C perfringens bacteremia in the setting of poorly differentiated high-grade endometrial malignancy.


2016 ◽  
Vol 199 (2) ◽  
Author(s):  
Nozomu Obana ◽  
Kouji Nakamura ◽  
Nobuhiko Nomura

ABSTRACT RNase Y is a major endoribonuclease that plays a crucial role in mRNA degradation and processing. We study the role of RNase Y in the Gram-positive anaerobic pathogen Clostridium perfringens, which until now has not been well understood. Our study implies an important role for RNase Y-mediated RNA degradation and processing in virulence gene expression and the physiological development of the organism. We began by constructing an RNase Y conditional knockdown strain in order to observe the importance of RNase Y on growth and virulence. Our resulting transcriptome analysis shows that RNase Y affects the expression of many genes, including toxin-producing genes. We provide data to show that RNase Y depletion repressed several toxin genes in C. perfringens and involved the virR-virS two-component system. We also observe evidence that RNase Y is indispensable for processing and stabilizing the transcripts of colA (encoding a major toxin collagenase) and pilA2 (encoding a major pilin component of the type IV pili). Posttranscriptional regulation of colA is known to be mediated by cleavage in the 5′ untranslated region (5′UTR), and we observe that RNase Y depletion diminishes colA 5′UTR processing. We show that RNase Y is also involved in the posttranscriptional stabilization of pilA2 mRNA, which is thought to be important for host cell adherence and biofilm formation. IMPORTANCE RNases have important roles in RNA degradation and turnover in all organisms. C. perfringens is a Gram-positive anaerobic spore-forming bacterial pathogen that produces numerous extracellular enzymes and toxins, and it is linked to digestive disorders and disease. A highly conserved endoribonuclease, RNase Y, affects the expression of hundreds of genes, including toxin genes, and studying these effects is useful for understanding C. perfringens specifically and RNases generally. Moreover, RNase Y is involved in processing specific transcripts, and we observed that this processing in C. perfringens results in the stabilization of mRNAs encoding a toxin and bacterial extracellular apparatus pili. Our study shows that RNase activity is associated with gene expression, helping to determine the growth, proliferation, and virulence of C. perfringens.


2009 ◽  
Vol 77 (10) ◽  
pp. 4421-4428 ◽  
Author(s):  
Martina Chiarezza ◽  
Dena Lyras ◽  
Sacha J. Pidot ◽  
Marietta Flores-Díaz ◽  
Milena M. Awad ◽  
...  

ABSTRACT The essential toxin in Clostridium perfringens-mediated gas gangrene or clostridial myonecrosis is alpha-toxin, although other toxins and extracellular enzymes may also be involved. In many bacterial pathogens extracellular sialidases are important virulence factors, and it has been suggested that sialidases may play a role in gas gangrene. C. perfringens strains have combinations of three different sialidase genes, two of which, nanI and nanJ, encode secreted sialidases. The nanI and nanJ genes were insertionally inactivated by homologous recombination in derivatives of sequenced strain 13 and were shown to encode two functional secreted sialidases, NanI and NanJ. Analysis of these derivatives showed that NanI was the major sialidase in this organism. Mutation of nanI resulted in loss of most of the secreted sialidase activity, and the residual activity was eliminated by subsequent mutation of the nanJ gene. Only a slight reduction in the total sialidase activity was observed in a nanJ mutant. Cytotoxicity assays using the B16 melanoma cell line showed that supernatants containing NanI or overexpressing NanJ enhanced alpha-toxin-mediated cytotoxicity. Finally, the ability of nanI, nanJ, and nanIJ mutants to cause disease was assessed in a mouse myonecrosis model. No attenuation of virulence was observed for any of these strains, providing evidence that neither the NanI sialidase nor the NanJ sialidase is essential for virulence.


2008 ◽  
Vol 212 (S 1) ◽  
Author(s):  
CA Hanke ◽  
R Hentschel ◽  
R Berner ◽  
A Superti-Furga ◽  
KD Rückauer ◽  
...  

2020 ◽  
pp. 16-18
Author(s):  
V. M. Lykhman ◽  
O. M. Shevchenko ◽  
Ye. O. Bilodid ◽  
Igor Vladimirovich Volchenko ◽  
I. A. Kulyk ◽  
...  

Among urgent surgical diseases of abdominal cavity, an acute intestinal obstruction is the most difficult to be diagnosed and treated. Leading factor, determining the development of pathophysiological processes is considered to be the progressive manifestations of enteric insufficiency syndrome, resulting in intestinal barrier impairment, negative changes in ecology of intestinal flora, increased endotoxins. To identify the small intestine microflora in acute intestinal obstruction and determine the role of dysbiotic disorders in clinical manifestations of main pathological process, a study was conducted in 60 patients with mechanical intestinal obstruction. The small intestine has a relatively rare microflora, consisting mainly of gram−positive facultative aerobic microorganisms, streptococci, lactobacilli. The distal ileum in nearly 30−55 % of healthy people contains scanty microflora, and yet the flora of this area differs from the microbial population of the higher gastrointestinal tract due to higher concentration of gram−negative bacteria. Optional−anaerobic coliform bacilli, anaerobic bifidobacteria and fusobacteria, bacteroids, the number of which starts exceeding the one of gram−positive species, are presented in significant quantities. Distal to the ileocecal valve there are significant changes in the microflora quantitative and species composition. Obligatory anaerobic bacteria become the predominant part of microflora, exceeding the number of aerobic and facultative anaerobic bacteria. The bacterial flora in different parts of gastrointestinal tract has its own specifics and is quite constant, as a result of the interaction of many factors, regulating the bacterial population in small intestine. The most important among them are: acidity of gastric juice, normal peristaltic activity of the intestine, bacterial interactions and immune mechanisms. Disorders of the intestine motor and evacuation function with its obstruction lead to slow passage of the chyme and contamination of the upper gastrointestinal tract with new types of microbes. There is a syndrome of small intestine excessive colonization, which means an increased concentration of bacterial populations in it, similar in species composition to the colon microflora. Pathological intra−intestinal contents become a source of endogenous infection and re−infection of the patient, leads to internal digestive disorders, which is manifested by syndrome of malabsorption of proteins, carbohydrates and vitamins. Key words: acute intestinal obstruction, small intestinal microflora, conditionally pathogenic microorganisms, intestinal biocenosis.


Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 245
Author(s):  
Hiroshi Sekiya ◽  
Maho Okada ◽  
Eiji Tamai ◽  
Toshi Shimamoto ◽  
Tadashi Shimamoto ◽  
...  

Clostridium perfringens is an often-harmful intestinal bacterium that causes various diseases ranging from food poisoning to life-threatening fulminant disease. Potential treatments include phage-derived endolysins, a promising family of alternative antimicrobial agents. We surveyed the genome of the C. perfringens st13 strain and identified an endolysin gene, psa, in the phage remnant region. Psa has an N-terminal catalytic domain that is homologous to the amidase_2 domain, and a C-terminal domain of unknown function. psa and gene derivatives encoding various Psa subdomains were cloned and expressed in Escherichia coli as N-terminal histidine-tagged proteins. Purified His-tagged full-length Psa protein (Psa-his) showed C. perfringens-specific lytic activity in turbidity reduction assays. In addition, we demonstrated that the uncharacterized C-terminal domain has cell wall-binding activity. Furthermore, cell wall-binding measurements showed that Psa binding was highly specific to C. perfringens. These results indicated that Psa is an amidase endolysin that specifically lyses C. perfringens; the enzyme’s specificity is highly dependent on the binding of the C-terminal domain. Moreover, Psa was shown to have a synergistic effect with another C. perfringens-specific endolysin, Psm, which is a muramidase that cleaves peptidoglycan at a site distinct from that targeted by Psa. The combination of Psa and Psm may be effective in the treatment and prevention of C. perfringens infections.


Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 266
Author(s):  
Thea Neumann ◽  
Maren Krüger ◽  
Jasmin Weisemann ◽  
Stefan Mahrhold ◽  
Daniel Stern ◽  
...  

Clostridium perfringens enterotoxin (CPE) regularly causes food poisoning and antibiotic-associated diarrhea; therefore, reliable toxin detection is crucial. To this aim, we explored stationary and mobile strategies to detect CPE either exclusively by monoclonal antibodies (mAbs) or, alternatively, by toxin-enrichment via the cellular receptor of CPE, claudin-4, and mAb detection. Among the newly generated mAbs, we identified nine CPE-specific mAbs targeting five distinct epitopes, among them mAbs recognizing CPE bound to claudin-4 or neutralizing CPE activity in vitro. In surface plasmon resonance experiments, all mAbs and claudin-4 revealed excellent affinities towards CPE, ranging from 0.05 to 2.3 nM. Integrated into sandwich enzyme-linked immunosorbent assays (ELISAs), the most sensitive mAb/mAb and claudin-4/mAb combinations achieved similar detection limits of 0.3 pg/mL and 1.0 pg/mL, respectively, specifically detecting recombinant CPE from spiked feces and native CPE from 30 different C. perfringens culture supernatants. The implementation of mAb- and receptor-based ELISAs into a mobile detection platform enabled the fast detection of CPE, which will be helpful in clinical laboratories to diagnose diarrhea of assumed bacterial origin. In conclusion, we successfully employed an endogenous receptor and novel high affinity mAbs for highly sensitive and specific CPE-detection. These tools will be useful for both basic and applied research.


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