Review

Authors: Irina V Pinchuk, Ellen J Beswick, Victor E Reyes...

Staphylococcus aureus (S. aureus) is a Gram positive bacterium that is carried by about one third of the general population and is responsible for common and serious diseases. These diseases include food poisoning and toxic shock syndrome, which are caused by exotoxins produced by S. aureus. Of the more than 20 Staphylococcal enterotoxins, SEA and SEB are the best characterized and are also regarded as superantigens because of their ability to bind to class II MHC molecules on antigen presenting cells and stimulate large populations of T cells that share variable regions on the β chain of the T cell receptor. The result of this massive T cell activation is a cytokine bolus leading to an acute toxic shock. These proteins are highly resistant to denaturation, which allows them to remain intact in contaminated food and trigger disease outbreaks. A recognized problem is the emergence of multi-drug resistant strains of S. aureus and these are a concern in the clinical setting as they are a common cause of antibiotic-associated diarrhea in hospitalized patients. In this review, we provide an overview of the current understanding of these proteins.

Topics: Animals; Biological Warfare Agents; Diarrhea; Enterotoxins; Humans; Staphylococcal Food Poisoning; Staphylococcus aureus; Superantigens

PubMed: 22069679
DOI: 10.3390/toxins2082177

Review

Authors: John C Freedman, Archana Shrestha, Bruce A McClane...

Clostridium perfringens enterotoxin (CPE) is responsible for causing the gastrointestinal symptoms of several C. perfringens food- and nonfood-borne human gastrointestinal diseases. The enterotoxin gene (cpe) is located on either the chromosome (for most C. perfringens type A food poisoning strains) or large conjugative plasmids (for the remaining type A food poisoning and most, if not all, other CPE-producing strains). In all CPE-positive strains, the cpe gene is strongly associated with insertion sequences that may help to assist its mobilization and spread. During disease, CPE is produced when C. perfringens sporulates in the intestines, a process involving several sporulation-specific alternative sigma factors. The action of CPE starts with its binding to claudin receptors to form a small complex; those small complexes then oligomerize to create a hexameric prepore on the membrane surface. Beta hairpin loops from the CPE molecules in the prepore assemble into a beta barrel that inserts into the membrane to form an active pore that enhances calcium influx, causing cell death. This cell death results in intestinal damage that causes fluid and electrolyte loss. CPE is now being explored for translational applications including cancer therapy/diagnosis, drug delivery, and vaccination.

Topics: Animals; Enterotoxins; Gastrointestinal Diseases; Humans; Vaccines

PubMed: 26999202
DOI: 10.3390/toxins8030073

Authors: Jieun Jung, Hyeonsuk Jin, Seungmi Seo...

This study aims to investigate the enterotoxin profiles and antibiotic susceptibility of isolated from garlic chives and environmental samples. A total of 103 isolates were used to identify enterotoxin genes, including , and . The hemolysin BL enterotoxin complex () was detected in 38 isolates (36.9%), and the non-hemolytic enterotoxin complex () was detected in 8 (7.8%) isolates. Forty-five isolates (43.7%) had and genes. was resistant to β-lactam antibiotics and susceptible to non-β-lactam antibiotics. However, some strains showed intermediate resistance to β-lactam and non-β-lactam antibiotics. isolated from garlic chives showed intermediate resistance to cefotaxime (7.7%), rifampin (15.4%), clindamycin (30.8%), erythromycin (7.7%), and tetracycline (7.7%). isolates from the agricultural environment were moderately resistant to cefotaxime (18.9%), rifampin (15.6%), clindamycin (12.2%), erythromycin (4.4%), and tetracycline (5.6%). Moreover, isolates from garlic chives and cultivation environments could change their antibiotic resistance profile from susceptible to intermediate-resistant to rifampin, clindamycin, erythromycin, and tetracycline and exhibit multidrug resistance. These results indicate that continuous monitoring of contamination in the produce and agricultural environment might be needed to ensure the safety of consuming fresh vegetables.

Topics: Anti-Bacterial Agents; Bacillus cereus; Cefotaxime; Chive; Clindamycin; Enterotoxins; Erythromycin; Food Microbiology; Garlic; Hemolysin Proteins; Lactams; Rifampin; Tetracyclines

PubMed: 36231461
DOI: 10.3390/ijerph191912159

Review

Authors: M Podkowik, J Y Park, K S Seo...

Staphylococci are a worldwide cause of human and animal infections including life-threatening cases of bacteraemia, wound infections, pyogenic lesions, and mastitis. Enterotoxins produced by some staphylococcal species were recognized as causative agents of staphylococcal food poisoning (SFP), being also able to interrupt human and animal immune responses. Only enterotoxins produced by Staphylococcus aureus were as yet well characterized. Much less is known about enterotoxigenic potential of coagulase-negative species of genus Staphylococcus (CNS). The pathogenic role of CNS and their enterotoxigenicity in developing SFP has not been well established. Although it has been reported that enterotoxigenic CNS strains have been associated with human and animal infections and food poisoning, most of research lacked a deeper insight into structure of elements encoding CNS enterotoxins. Recent studies provided us with strong evidence for the presence and localization of enterotoxin-coding elements in CNS genomes and production of enterotoxins. Thus, the importance of pathogenic potential of CNS as a source of staphylococcal enterotoxins has been highlighted in human and animal infections as well as in food poisoning.

Topics: Animals; Coagulase; Enterotoxins; Humans; Staphylococcal Food Poisoning; Staphylococcal Infections; Staphylococcus

PubMed: 23500613
DOI: 10.1016/j.ijfoodmicro.2013.02.005

Review

Authors: Cassidy Prince, Jasna Kovac

Bacillus cereus sensu lato () includes foodborne pathogens, as well as beneficial microorganisms, such as bioinsecticides. Some of the beneficial and commercially used B. cereus strains have been shown to carry enterotoxin genes, the products of which can cause toxicoinfection in humans. Furthermore, recent epidemiological reports indicated that some bioinsecticidal strains have been linked with foodborne illness outbreaks. This demonstrates the need for improved surveillance of B. cereus which includes characterization of isolates' virulence capacity. However, the prediction of virulence capacity of B. cereus strains is challenging. Genetic screening for enterotoxin gene presence has proven to be insufficient for accurate discrimination between virulent and avirulent strains, given that nearly all B. cereus strains carry at least one enterotoxin gene. Furthermore, complex regulatory networks governing the expression of enterotoxins, and potential synergistic interactions between enterotoxins and other virulence factors make the prediction of toxicoinfection based on isolates' genome sequences challenging. In this review, we summarize and synthesize the current understanding of the regulation of enterotoxins associated with the B. cereus toxicoinfection and identify gaps in the knowledge that need to be addressed to facilitate identification of genetic markers predictive of cytotoxicity and toxicoinfection.

Topics: Bacillus cereus; Enterotoxins; Food Microbiology; Foodborne Diseases; Humans; Virulence; Virulence Factors

PubMed: 35730937
DOI: 10.1128/aem.00405-22

Authors: William L Johnson, Michael Sohn, Collynn F Woeller...

PURPOSE

Staphylococcus aureus is an important cause of corneal infections (keratitis). To better understand the virulence mechanisms mediating keratitis, a recent comparative genomics study revealed that a set of secreted enterotoxins were found with higher prevalence among ocular versus non-ocular S. aureus clinical infection isolates, suggesting a key role for these toxins in keratitis. Although well known to cause toxic shock syndrome and S. aureus food poisoning, enterotoxins have not yet been shown to mediate virulence in keratitis.

METHODS

A set of clinical isolate test strains, including a keratitis isolate that encodes five enterotoxins (sed, sej, sek, seq, ser), its corresponding enterotoxin deletion mutant and complementation strain, a keratitis isolate devoid of enterotoxins, and the non-ocular S. aureus strain USA300 along with its corresponding enterotoxin deletion and complementation strains, were evaluated for cellular adhesion, invasion and cytotoxicity in a primary corneal epithelial model as well as with microscopy. Additionally, strains were evaluated in an in vivo model of keratitis to quantify enterotoxin gene expression and measure disease severity.

RESULTS

We demonstrate that, although enterotoxins do not impact bacterial adhesion or invasion, they do elicit direct cytotoxicity in vitro toward corneal epithelial cells. In an in vivo model, sed, sej, sek, seq, ser were found to have variable gene expression across 72 hours of infection and test strains encoding enterotoxins resulted in increased bacterial burden as well as a reduced host cytokine response.

CONCLUSIONS

Our results support a novel role for staphylococcal enterotoxins in promoting virulence in S. aureus keratitis.

Topics: Humans; Enterotoxins; Keratitis; Staphylococcal Infections; Staphylococcus aureus; Virulence

PubMed: 37133835
DOI: 10.1167/iovs.64.5.5

Review

Authors: Philipp R Weiglmeier, Paul Rösch, Hanna Berkner...

Enterotoxigenic Escherichia coli (ETEC) associated diarrhea is responsible for roughly half a million deaths per year, the majority taking place in developing countries. The main agent responsible for these diseases is the bacterial heat-stable enterotoxin STa. STa is secreted by ETEC and after secretion binds to the intestinal receptor guanylyl cyclase C (GC-C), thus triggering a signaling cascade that eventually leads to the release of electrolytes and water in the intestine. Additionally, GC-C is a specific marker for colorectal carcinoma and STa is suggested to have an inhibitory effect on intestinal carcinogenesis. To understand the conformational events involved in ligand binding to GC-C and to devise therapeutic strategies to treat both diarrheal diseases and colorectal cancer, it is paramount to obtain structural information on the receptor ligand system. Here we summarize the currently available structural data and report on physiological consequences of STa binding to GC-C in intestinal epithelia and colorectal carcinoma cells.

Topics: Amino Acid Sequence; Bacterial Toxins; Binding Sites; Cell Line, Tumor; Colorectal Neoplasms; Diarrhea; Enterotoxigenic Escherichia coli; Enterotoxins; Escherichia coli Infections; Escherichia coli Proteins; Host-Pathogen Interactions; Humans; Ligands; Molecular Sequence Data; Protein Binding; Protein Structure, Tertiary; Receptors, Guanylate Cyclase-Coupled

PubMed: 22069681
DOI: 10.3390/toxins2092213

Review

Authors: Teresa Krakauer, Bradley G Stiles

Staphylococcus aureus plays an important role in numerous human cases of food poisoning, soft tissue, and bone infections, as well as potentially lethal toxic shock. This common bacterium synthesizes various virulence factors that include staphylococcal enterotoxins (SEs). These protein toxins bind directly to major histocompatibility complex class II on antigen-presenting cells and specific Vβ regions of T-cell receptors, resulting in potentially life-threatening stimulation of the immune system. Picomolar concentrations of SEs ultimately elicit proinflammatory cytokines that can induce fever, hypotension, multi-organ failure, and lethal shock. Various in vitro and in vivo models have provided important tools for studying the biological effects of, as well as potential vaccines/therapeutics against, the SEs. This review succinctly presents known physical and biological properties of the SEs, including various intervention strategies. In particular, SEB will often be portrayed as per biodefense concerns dating back to the 1960s.

Topics: Cytokines; Enterotoxins; Humans; Multiple Organ Failure; Shock; Staphylococcus aureus; Superantigens

PubMed: 23959032
DOI: 10.4161/viru.23905

Authors: Tanja Buchacher, Astrid Digruber, Markus Kranzler...

BACKGROUND

Extracellular vesicles (EVs) from Gram-positive bacteria have gained considerable importance as a novel transport system of virulence factors in host-pathogen interactions. Bacillus cereus is a Gram-positive human pathogen, causing gastrointestinal toxemia as well as local and systemic infections. The pathogenicity of enteropathogenic B. cereus has been linked to a collection of virulence factors and exotoxins. Nevertheless, the exact mechanism of virulence factor secretion and delivery to target cells is poorly understood.

RESULTS

Here, we investigate the production and characterization of enterotoxin-associated EVs from the enteropathogenic B. cereus strain NVH0075-95 by using a proteomics approach and studied their interaction with human host cells in vitro. For the first time, comprehensive analyses of B. cereus EV proteins revealed virulence-associated factors, such as sphingomyelinase, phospholipase C, and the three-component enterotoxin Nhe. The detection of Nhe subunits was confirmed by immunoblotting, showing that the low abundant subunit NheC was exclusively detected in EVs as compared to vesicle-free supernatant. Cholesterol-dependent fusion and predominantly dynamin-mediated endocytosis of B. cereus EVs with the plasma membrane of intestinal epithelial Caco2 cells represent entry routes for delivery of Nhe components to host cells, which was assessed by confocal microscopy and finally led to delayed cytotoxicity. Furthermore, we could show that B. cereus EVs elicit an inflammatory response in human monocytes and contribute to erythrocyte lysis via a cooperative interaction of enterotoxin Nhe and sphingomyelinase.

CONCLUSION

Our results provide insights into the interaction of EVs from B. cereus with human host cells and add a new layer of complexity to our understanding of multicomponent enterotoxin assembly, offering new opportunities to decipher molecular processes involved in disease development. Video Abstract.

Topics: Humans; Enterotoxins; Bacillus cereus; Caco-2 Cells; Sphingomyelin Phosphodiesterase; Virulence Factors; Bacterial Proteins

PubMed: 37189133
DOI: 10.1186/s12964-023-01132-1

Authors: Paweł Kwiatkowski, Aleksandra Tabiś, Karol Fijałkowski...

The study aimed to examine the influence of a rotating magnetic field (RMF) of two different frequencies (5 and 50 Hz) on the expression of regulatory (, , ) and staphylococcal enterotoxin (SE-, , ) genes as well as the production of SEs (SEA, SEC, SEL) by the FRI913 strain cultured on a medium supplemented with a subinhibitory concentration of -anethole (TA). Furthermore, a theoretical model of interactions between the bacterial medium and bacterial cells exposed to RMF was proposed. Gene expression and SEs production were measured using quantitative real-time PCR and ELISA techniques, respectively. Based on the obtained results, it was found that there were no significant differences in the expression of regulatory and SE genes in bacteria simultaneously cultured on a medium supplemented with TA and exposed to RMF at the same time in comparison to the control (unexposed to TA and RMF). In contrast, when the bacteria were cultured on a medium supplemented with TA but were not exposed to RMF or when they were exposed to RMF of 50 Hz (but not to TA), a significant increase in and transcripts as compared to the unexposed control was found. Moreover, the decreased level of transcripts in bacteria cultured without TA but exposed to RMF of 50 Hz was also revealed. In turn, a significant increase in SEA and decrease in SEC and SEL production was observed in bacteria cultured on a medium supplemented with TA and simultaneously exposed to RMFs. It can be concluded, that depending on SE and regulatory genes expression as well as production of SEs, the effect exerted by the RMF and TA may be positive (i.e., manifests as the increase in SEs and/or regulatory gene expression of SEs production) or negative (i.e., manifests as the reduction in both aforementioned features) or none.

Topics: Allylbenzene Derivatives; Anisoles; Enterotoxins; Gene Expression; Humans; Magnetic Fields; Staphylococcal Infections; Staphylococcus aureus

PubMed: 35683006
DOI: 10.3390/ijms23116327