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FEMS Microbiology Reviews Jul 2023Bacillus thuringiensis (Bt) proteins are an environmentally safe and effective alternative to chemical pesticides and have been used as biopesticides, with great... (Review)
Review
Bacillus thuringiensis (Bt) proteins are an environmentally safe and effective alternative to chemical pesticides and have been used as biopesticides, with great commercial success, for over 50 years. Global agricultural production is predicted to require a 70% increase until 2050 to provide for an increasing population. In addition to agriculture, Bt proteins are utilized to control human vectors of disease-namely mosquitoes-which account for >700 000 deaths annually. The evolution of resistance to Bt pesticial toxins threatens the progression of sustainable agriculture. Whilst Bt protein toxins are heavily utilized, the exact mechanisms behind receptor binding and toxicity are unknown. It is critical to gain a better understanding of these mechanisms in order to engineer novel toxin variants and to predict, and prevent, future resistance evolution. This review focuses on the role of carbohydrate binding in the toxicity of the most utilized group of Bt pesticidal proteins-three domain Cry (3D-Cry) toxins.
Topics: Animals; Humans; Insecticides; Endotoxins; Bacterial Proteins; Hemolysin Proteins; Mosquito Vectors; Bacillus thuringiensis Toxins; Bacillus thuringiensis; Glycoconjugates
PubMed: 37279443
DOI: 10.1093/femsre/fuad026 -
Medical Mycology Jan 2013Hemolysins are a class of proteins defined by their ability to lyse red cells but have been described to exhibit pleiotropic functions. These proteins have been... (Review)
Review
Hemolysins are a class of proteins defined by their ability to lyse red cells but have been described to exhibit pleiotropic functions. These proteins have been extensively studied in bacteria and more recently in fungi. Within the last decade, a number of studies have characterized fungal hemolysins and revealed a fascinating yet diverse group of proteins. The purpose of this review is to provide a synopsis of the known fungal hemolysins with an emphasis on those belonging to the aegerolysin protein family. New insight and perspective into fungal hemolysins in biotechnology and health are additionally presented.
Topics: Biotechnology; Fungal Proteins; Fungi; Health; Hemolysin Proteins; Hemolysis; Virulence Factors
PubMed: 22769586
DOI: 10.3109/13693786.2012.698025 -
Journal of Thrombosis and Haemostasis :... Jun 2022Toxins are key virulence determinants of pathogens and can impair the function of host immune cells, including platelets. Insights into pathogen toxin interference with...
BACKGROUND
Toxins are key virulence determinants of pathogens and can impair the function of host immune cells, including platelets. Insights into pathogen toxin interference with platelets will be pivotal to improve treatment of patients with bacterial bloodstream infections.
MATERIALS AND METHODS
In this study, we deciphered the effects of Staphylococcus aureus toxins α-hemolysin, LukAB, LukDE, and LukSF on human platelets and compared the effects with the pore forming toxin pneumolysin of Streptococcus pneumoniae. Activation of platelets and loss of platelet function were investigated by flow cytometry, aggregometry, platelet viability, fluorescence microscopy, and intracellular calcium release. Thrombus formation was assessed in whole blood.
RESULTS
α-hemolysin (Hla) is known to be a pore-forming toxin. Hla-induced calcium influx initially activates platelets as indicated by CD62P and αIIbβ3 integrin activation, but also induces finally alterations in the phenotype of platelets. In contrast to Hla and pneumolysin, S. aureus bicomponent pore-forming leukocidins LukAB, LukED, and LukSF do not bind to platelets and had no significant effect on platelet activation and viability. The presence of small amounts of Hla (0.2 µg/ml) in whole blood abrogates thrombus formation indicating that in systemic infections with S. aureus the stability of formed thrombi is impaired. Damage of platelets by Hla was not neutralized by intravenous immune globulins.
CONCLUSION
Our findings might be of clinical relevance for S. aureus induced endocarditis. Stabilizing the aortic-valve thrombi by inhibiting Hla-induced impairment of platelets might reduce the risk for septic (micro-)embolization.
Topics: Bacterial Proteins; Calcium; Hemolysin Proteins; Humans; Leukocidins; Staphylococcal Infections; Staphylococcus aureus; Thrombosis
PubMed: 35303391
DOI: 10.1111/jth.15703 -
Clinical Microbiology Reviews Jan 2000This article reviews the literature regarding the structure and function of two types of exotoxins expressed by Staphylococcus aureus, pyrogenic toxin superantigens... (Review)
Review
This article reviews the literature regarding the structure and function of two types of exotoxins expressed by Staphylococcus aureus, pyrogenic toxin superantigens (PTSAgs) and hemolysins. The molecular basis of PTSAg toxicity is presented in the context of two diseases known to be caused by these exotoxins: toxic shock syndrome and staphylococcal food poisoning. The family of staphylococcal PTSAgs presently includes toxic shock syndrome toxin-1 (TSST-1) and most of the staphylococcal enterotoxins (SEs) (SEA, SEB, SEC, SED, SEE, SEG, and SEH). As the name implies, the PTSAgs are multifunctional proteins that invariably exhibit lethal activity, pyrogenicity, superantigenicity, and the capacity to induce lethal hypersensitivity to endotoxin. Other properties exhibited by one or more staphylococcal PTSAgs include emetic activity (SEs) and penetration across mucosal barriers (TSST-1). A detailed review of the molecular mechanisms underlying the toxicity of the staphylococcal hemolysins is also presented.
Topics: Exotoxins; Hemolysin Proteins; Humans; Leukocidins; Staphylococcal Infections; Staphylococcus aureus
PubMed: 10627489
DOI: 10.1128/CMR.13.1.16 -
Microbiology and Immunology Nov 2021The genus Streptococcus infects a broad range of hosts, including humans. Some species, such as S. pyogenes, S. agalactiae, S. pneumoniae, and S. mutans, are recognized... (Review)
Review
The genus Streptococcus infects a broad range of hosts, including humans. Some species, such as S. pyogenes, S. agalactiae, S. pneumoniae, and S. mutans, are recognized as the major human pathogens, and their pathogenicity toward humans has been investigated. However, many of other streptococcal species have been recognized as opportunistic pathogens in humans, and their clinical importance has been underestimated. In our previous study, the Anginosus group streptococci (AGS) and Mitis group streptococci (MGS) showed clear β-hemolysis on blood agar, and the factors responsible for the hemolysis were homologs of two types of β-hemolysins, cholesterol-dependent cytolysin (CDC) and streptolysin S (SLS). In contrast to the regular β-hemolysins produced by streptococci (typical CDCs and SLSs), genetically, structurally, and functionally atypical β-hemolysins have been observed in AGS and MGS. These atypical β-hemolysins are thought to affect and contribute to the pathogenic potential of opportunistic streptococci mainly inhabiting the human oral cavity. In this review, we introduce the diverse characteristics of β-hemolysin produced by opportunistic streptococci, focusing on the species/strains belonging to AGS and MGS, and discuss their pathogenic potential.
Topics: Hemolysin Proteins; Hemolysis; Humans; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes
PubMed: 34591320
DOI: 10.1111/1348-0421.12936 -
Journal of Food Protection Feb 2018The growth and hemolytic activity profiles of two Vibrio parahaemolyticus strains (ATCC 17802 and ATCC 33847) in shrimp, oyster, freshwater fish, pork, chicken, and egg...
The growth and hemolytic activity profiles of two Vibrio parahaemolyticus strains (ATCC 17802 and ATCC 33847) in shrimp, oyster, freshwater fish, pork, chicken, and egg fried rice were investigated, and a prediction system for accurate microbial risk assessment was developed. The two V. parahaemolyticus strains displayed a similar growth and hemolysin production pattern in the foods at 37°C. Growth kinetic parameters showed that V. parahaemolyticus displayed higher maximum specific growth rate and shorter lag time values in shrimp > freshwater fish > egg fried rice> oyster > chicken > pork. Notably, there was a similar number of V. parahaemolyticus in all of these samples at the stationary phase. The hemolytic activity of V. parahaemolyticus in foods increased linearly with time ( R > 0.97). The rate constant ( K) of hemolytic activity was higher in shrimp, oyster, freshwater fish, and egg fried rice than in pork and chicken. Significantly higher hemolytic activity of V. parahaemolyticus was evident in egg fried rice > shrimp > freshwater fish > chicken > oyster > pork. The above-mentioned results indicate that V. parahaemolyticus could grow well regardless of the food type and that contrary to current belief, it displayed a higher hemolytic activity in some nonseafood products (freshwater fish, egg fried rice, and chicken) than in one seafood (oyster). The prediction system consisting of the growth model and hemolysin production algorithm reported here will fill a gap in predictive microbiology and improve significantly the accuracy of microbial risk assessment of V. parahaemolyticus.
Topics: Animals; Food Microbiology; Hemolysin Proteins; Vibrio parahaemolyticus
PubMed: 29360402
DOI: 10.4315/0362-028X.JFP-17-308 -
Toxins Jun 2013The Bacillus cereus sensu lato group contains diverse Gram-positive spore-forming bacteria that can cause gastrointestinal diseases and severe eye infections in humans.... (Review)
Review
The Bacillus cereus sensu lato group contains diverse Gram-positive spore-forming bacteria that can cause gastrointestinal diseases and severe eye infections in humans. They have also been incriminated in a multitude of other severe, and frequently fatal, clinical infections, such as osteomyelitis, septicaemia, pneumonia, liver abscess and meningitis, particularly in immuno-compromised patients and preterm neonates. The pathogenic properties of this organism are mediated by the synergistic effects of a number of virulence products that promote intestinal cell destruction and/or resistance to the host immune system. This review focuses on the pore-forming haemolysins produced by B. cereus: haemolysin I (cereolysin O), haemolysin II, haemolysin III and haemolysin IV (CytK). Haemolysin I belongs to the cholesterol-dependent cytolysin (CDC) family whose best known members are listeriolysin O and perfringolysin O, produced by L. monocytogenes and C. perfringens respectively. HlyII and CytK are oligomeric ß-barrel pore-forming toxins related to the α-toxin of S. aureus or the ß-toxin of C. perfringens. The structure of haemolysin III, the least characterized haemolytic toxin from the B. cereus, group has not yet been determined.
Topics: Bacillus cereus; Bacterial Toxins; Hemolysin Proteins; Protein Conformation
PubMed: 23748204
DOI: 10.3390/toxins5061119 -
Toxins May 2015The anaerobic bacterium Clostridium perfringens expresses multiple toxins that promote disease development in both humans and animals. One such toxin is perfringolysin O... (Review)
Review
The anaerobic bacterium Clostridium perfringens expresses multiple toxins that promote disease development in both humans and animals. One such toxin is perfringolysin O (PFO, classically referred to as θ toxin), a pore-forming cholesterol-dependent cytolysin (CDC). PFO is secreted as a water-soluble monomer that recognizes and binds membranes via cholesterol. Membrane-bound monomers undergo structural changes that culminate in the formation of an oligomerized prepore complex on the membrane surface. The prepore then undergoes conversion into the bilayer-spanning pore measuring approximately 250-300 Å in diameter. PFO is expressed in nearly all identified C. perfringens strains and harbors interesting traits that suggest a potential undefined role for PFO in disease development. Research has demonstrated a role for PFO in gas gangrene progression and bovine necrohemorrhagic enteritis, but there is limited data available to determine if PFO also functions in additional disease presentations caused by C. perfringens. This review summarizes the known structural and functional characteristics of PFO, while highlighting recent insights into the potential contributions of PFO to disease pathogenesis.
Topics: Animals; Bacterial Toxins; Cell Membrane; Clostridium perfringens; Hemolysin Proteins; Humans
PubMed: 26008232
DOI: 10.3390/toxins7051702 -
FEMS Microbiology Reviews Sep 2014Group B streptococcus [(GBS or Streptococcus agalactiae)] is a leading cause of neonatal meningitis and septicaemia. Most clinical isolates express simultaneously a... (Review)
Review
Group B streptococcus [(GBS or Streptococcus agalactiae)] is a leading cause of neonatal meningitis and septicaemia. Most clinical isolates express simultaneously a β-haemolysin/cytolysin and a red polyenic pigment, two phenotypic traits important for GBS identification in medical microbiology. The genetic determinants encoding the GBS haemolysin and pigment have been elucidated and the molecular structure of the pigment has been determined. The cyl operon involved in haemolysin and pigment production is regulated by the major two-component system CovS/R, which coordinates the expression of multiple virulence factors of GBS. Genetic analyses indicated strongly that the haemolysin activity was due to a cytolytic toxin encoded by cylE. However, the biochemical nature of the GBS haemolysin has remained elusive for almost a century because of its instability during purification procedures. Recently, it has been suggested that the haemolytic and cytolytic activity of GBS is due to the ornithine rhamnopolyenic pigment and not to the CylE protein. Here we review and summarize our current knowledge of the genetics, regulation and biochemistry of these twin GBS phenotypic traits, including their functions as GBS virulence factors.
Topics: Animals; Bacterial Proteins; Hemolysin Proteins; Humans; Multigene Family; Operon; Pigments, Biological; Streptococcal Infections; Streptococcus agalactiae; Virulence Factors
PubMed: 24617549
DOI: 10.1111/1574-6976.12071 -
Toxins Jun 2019Cytolytic leukotoxins of the repeat in toxin (RTX) family are large proteins excreted by gram-negative bacterial pathogens through the type 1 secretion system (T1SS)....
Cytolytic leukotoxins of the repeat in toxin (RTX) family are large proteins excreted by gram-negative bacterial pathogens through the type 1 secretion system (T1SS). Due to low yields and poor stability in cultures of the original pathogens, it is useful to purify recombinant fatty-acylated RTX cytolysins from inclusion bodies produced in . Such preparations are, however, typically contaminated by high amounts of lipopolysaccharide (LPS or endotoxin). We report a simple procedure for purification of large amounts of biologically active and endotoxin-free RTX toxins. It is based on the common feature of RTX cytolysins that are T1SS-excreted as unfolded polypeptides and fold into a biologically active toxin only upon binding of calcium ions outside of the bacterial cell. Mimicking this process, the RTX proteins are solubilized from inclusion bodies with buffered 8 M urea, bound onto a suitable chromatographic medium under denaturing conditions and the contaminating LPS is removed through extensive on-column washes with buffers containing 6 to 8 M urea and 1% Triton X-100 or Triton X-114. Extensive on-column rinsing with 8 M urea buffer removes residual detergent and the eluted highly active RTX protein preparations then contain only trace amounts of LPS. The procedure is exemplified using four prototypic RTX cytolysins, the CyaA and the hemolysins of (HlyA), (RtxA), and (ApxIA).
Topics: Animals; Bacterial Proteins; Cell Line, Tumor; Cell Survival; Cytotoxins; Detergents; Erythrocytes; Escherichia coli; Hemolysin Proteins; Hemolysis; Humans; Lipopolysaccharides; Octoxynol; Sheep; THP-1 Cells; Urea
PubMed: 31212877
DOI: 10.3390/toxins11060336