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Keywords = alpha-hemolysin

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28 pages, 10223 KiB  
Article
Theoretical Study of Sphingomyelinases from Entamoeba histolytica and Trichomonas vaginalis Sheds Light on the Evolution of Enzymes Needed for Survival and Colonization
by Fátima Berenice Ramírez-Montiel, Sairy Yarely Andrade-Guillen, Ana Laura Medina-Nieto, Ángeles Rangel-Serrano, José A. Martínez-Álvarez, Javier de la Mora, Naurú Idalia Vargas-Maya, Claudia Leticia Mendoza-Macías, Felipe Padilla-Vaca and Bernardo Franco
Pathogens 2025, 14(1), 32; https://doi.org/10.3390/pathogens14010032 - 5 Jan 2025
Viewed by 1377
Abstract
The path to survival for pathogenic organisms is not straightforward. Pathogens require a set of enzymes for tissue damage generation and to obtain nourishment, as well as a toolbox full of alternatives to bypass host defense mechanisms. Our group has shown that the [...] Read more.
The path to survival for pathogenic organisms is not straightforward. Pathogens require a set of enzymes for tissue damage generation and to obtain nourishment, as well as a toolbox full of alternatives to bypass host defense mechanisms. Our group has shown that the parasitic protist Entamoeba histolytica encodes for 14 sphingomyelinases (SMases); one of them (acid sphingomyelinase 6, aSMase6) is involved in repairing membrane damage and exhibits hemolytic activity. The enzymatic characterization of aSMase6 has been shown to be activated by magnesium ions but not by zinc, as shown for the human aSMase, and is strongly inhibited by cobalt. However, no structural data are available for the aSMase6 enzyme. In this work, bioinformatic analyses showed that the protist aSMases are diverse enzymes, are evolutionarily related to hemolysins derived from bacteria, and showed a similar overall structure as parasitic, free-living protists and mammalian enzymes. AlphaFold3 models predicted the occupancy of cobalt ions in the active site of the aSMase6 enzyme. Cavity blind docking showed that the substrate is pushed outward of the active site when cobalt is bound instead of magnesium ions. Additionally, the structural models of the aSMase6 of E. histolytica showed a loop that is absent from the rest of the aSMases, suggesting that it may be involved in hemolytic activity, as demonstrated experimentally using the recombinant proteins of aSMase4 and aSMase6. Trichomonas vaginalis enzymes show a putative transmembrane domain and seem functionally different from E. histolytica. This work provides insight into the future biochemical analyses that can show mechanistic features of parasitic protists sphingomyelinases, ultimately rendering these enzymes potential therapeutic targets. Full article
(This article belongs to the Special Issue Computational Approaches in Mechanisms of Pathogenesis)
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19 pages, 13924 KiB  
Article
Purinergic Receptor Antagonists Inhibit Hemolysis Induced by Clostridium perfringens Alpha Toxin
by Zishuo Guo, Nan Yue, Ming Chen, Jiaxin Li, Ruomei Lv, Jing Wang, Tingting Liu, Jing Huang, Shan Gao, Yanwei Li, Bing Yuan, Jinglin Wang, Lin Kang, Bin Ji and Wenwen Xin
Pathogens 2024, 13(6), 454; https://doi.org/10.3390/pathogens13060454 - 27 May 2024
Cited by 1 | Viewed by 1421
Abstract
Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in [...] Read more.
Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for Staphylococcus aureus β-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis. Full article
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15 pages, 6695 KiB  
Article
Interaction of Carbon Nanotubes, Capped Carbon Nanotubes, CNT2–5, C60, C70, HO-C60, [C60]2, and [C60]3 Fullerenes with Virulence Factors of Gram-Negative and Gram-Positive Bacteria: Potential Applications for 3D-Printed Scaffolds
by Mehran Alavi, Morahem Ashengroph and M. R. Mozafari
Inorganics 2024, 12(3), 77; https://doi.org/10.3390/inorganics12030077 - 1 Mar 2024
Cited by 6 | Viewed by 3248
Abstract
The antimicrobial application of carbon nanomaterials, such as carbon nanotubes (CNTs), capped CNTs, CNT2–5, C60, C70, HO-C60, [C60]2, and [C60]3 fullerenes, is increasing, owing to their low cytotoxicity [...] Read more.
The antimicrobial application of carbon nanomaterials, such as carbon nanotubes (CNTs), capped CNTs, CNT2–5, C60, C70, HO-C60, [C60]2, and [C60]3 fullerenes, is increasing, owing to their low cytotoxicity properties compared to other nanomaterials such as metallic nanoparticles. Enhanced mechanical properties and antibacterial activity can be caused by the incorporation of CNTs in 3-dimensional (3D) printed nanocomposites (NCs). The interruption of the bacterial membrane resulting from the cylindrical shape and high aspect ratio properties has been found to be the most prominent antibacterial mechanism of CNTs. However, the unraveling interaction of CNTs, capped CNTs, CNT2–5, C60, C70, HO-C60, [C60]2, and [C60]3 fullerenes with virulence factors of the main bacterial pathogenesis has not yet been understood. Therefore, in the present study, interactions of these carbon-based nanomaterials with the eight virulence factors, including protein kinase A and (ESX)-secreted protein B of Mycobacterium tuberculosis, pseudomonas elastase and exotoxin A of Pseudomonas aeruginosa, alpha-hemolysin and penicillin-binding protein 2a of Staphylococcus aureus, and shiga toxin 2a and heat-labile enterotoxin of Escherichia coli, were evaluated with the molecular docking method of AutoDock Vina. This study disclosed that the binding affinity was highest for CNT2–5 and [C60]3 toward alpha-hemolysin, with binding energies of −32.7 and −26.6 kcal/mol, respectively. The stability of the CNT2–5–alpha-hemolysin complex at different times was obtained according to the normal mode analysis of ElNémo and iMOD servers. Full article
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21 pages, 3473 KiB  
Article
Investigation of Staphylococcus aureus Biofilm-Associated Toxin as a Potential Squamous Cell Carcinoma Therapeutic
by Zi Xin Ong, Bavani Kannan, Anthony R. J. Phillips and David L. Becker
Microorganisms 2024, 12(2), 293; https://doi.org/10.3390/microorganisms12020293 - 30 Jan 2024
Cited by 3 | Viewed by 2163
Abstract
Cancer therapies developed using bacteria and their components have been around since the 19th century. Compared to traditional cancer treatments, the use of bacteria-derived compounds as cancer therapeutics could offer a higher degree of specificity, with minimal off-target effects. Here, we explored the [...] Read more.
Cancer therapies developed using bacteria and their components have been around since the 19th century. Compared to traditional cancer treatments, the use of bacteria-derived compounds as cancer therapeutics could offer a higher degree of specificity, with minimal off-target effects. Here, we explored the use of soluble bacteria-derived toxins as a potential squamous cell carcinoma (SCC) therapeutic. We optimized a protocol to generate Staphylococcus aureus biofilm-conditioned media (BCM), where soluble bacterial products enriched in the development of biofilms were isolated from a bacterial culture and applied to SCC cell lines. Bioactive components of S. aureus ATCC 29213 (SA29213) BCM display selective toxicity towards cancerous human skin SCC-12 at low doses, while non-cancerous human keratinocyte HaCaT and fibroblast BJ-5ta are minimally affected. SA29213 BCM treatment causes DNA damage to SCC-12 and initiates Caspase 3-dependent-regulated cell death. The use of the novel SA29213 bursa aurealis transposon mutant library led to the identification of S. aureus alpha hemolysin as the main bioactive compound responsible for the observed SCC-12-specific toxicity. The antibody neutralisation of Hla eradicates the cytotoxicity of SA29213 BCM towards SCC-12. Hla displays high SCC-12-specific toxicity, which is exerted primarily through Hla-ADAM10 interaction, Hla oligomerisation, and pore formation. The high target specificity and potential to cause cell death in a controlled manner highlight SA29213 Hla as a good candidate as an alternative SCC therapeutic. Full article
(This article belongs to the Section Biofilm)
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13 pages, 4670 KiB  
Article
Diflunisal Attenuates Virulence Factor Gene Regulation and Phenotypes in Staphylococcus aureus
by Liana C. Chan, Mihyun Park, Hong K. Lee, Siyang Chaili, Yan Q. Xiong, Arnold S. Bayer, Richard A. Proctor and Michael R. Yeaman
Antibiotics 2023, 12(5), 902; https://doi.org/10.3390/antibiotics12050902 - 13 May 2023
Cited by 6 | Viewed by 2165
Abstract
Virulence factor expression is integral to pathogenicity of Staphylococcus aureus. We previously demonstrated that aspirin, through its major metabolite, salicylic acid (SAL), modulates S. aureus virulence phenotypes in vitro and in vivo. We compared salicylate metabolites and a structural analogue for their [...] Read more.
Virulence factor expression is integral to pathogenicity of Staphylococcus aureus. We previously demonstrated that aspirin, through its major metabolite, salicylic acid (SAL), modulates S. aureus virulence phenotypes in vitro and in vivo. We compared salicylate metabolites and a structural analogue for their ability to modulate S. aureus virulence factor expression and phenotypes: (i) acetylsalicylic acid (ASA, aspirin); (ii) ASA metabolites, salicylic acid (SAL), gentisic acid (GTA) and salicyluric acid (SUA); or (iii) diflunisal (DIF), a SAL structural analogue. None of these compounds altered the growth rate of any strain tested. ASA and its metabolites SAL, GTA and SUA moderately impaired hemolysis and proteolysis phenotypes in multiple S. aureus strain backgrounds and their respective deletion mutants. Only DIF significantly inhibited these virulence phenotypes in all strains. The kinetic profiles of ASA, SAL or DIF on expression of hla (alpha hemolysin), sspA (V8 protease) and their regulators (sigB, sarA, agr (RNAIII)) were assessed in two prototypic strain backgrounds: SH1000 (methicillin-sensitive S. aureus; MSSA) and LAC-USA300 (methicillin-resistant S. aureus; MRSA). DIF induced sigB expression which is coincident with the significant inhibition of RNAIII expression in both strains and precedes significant reductions in hla and sspA expression. The inhibited expression of these genes within 2 h resulted in the durable suppression of hemolysis and proteolysis phenotypes. These results indicate that DIF modulates the expression of key virulence factors in S. aureus via a coordinated impact on their relevant regulons and target effector genes. This strategy may hold opportunities to develop novel antivirulence strategies to address the ongoing challenge of antibiotic-resistant S. aureus. Full article
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15 pages, 3357 KiB  
Article
Effect of Essential Oil from Lippia origanoides on the Transcriptional Expression of Genes Related to Quorum Sensing, Biofilm Formation, and Virulence of Escherichia coli and Staphylococcus aureus
by Andrés Martínez, Elena E. Stashenko, Rodrigo Torres Sáez, German Zafra and Claudia Ortiz
Antibiotics 2023, 12(5), 845; https://doi.org/10.3390/antibiotics12050845 - 3 May 2023
Cited by 19 | Viewed by 3651
Abstract
Microbial infections resistant to conventional antibiotics constitute one of the most important causes of mortality in the world. In some bacterial species, such as Escherichia coli and Staphylococcus aureus pathogens, biofilm formation can favor their antimicrobial resistance. These biofilm-forming bacteria produce a compact [...] Read more.
Microbial infections resistant to conventional antibiotics constitute one of the most important causes of mortality in the world. In some bacterial species, such as Escherichia coli and Staphylococcus aureus pathogens, biofilm formation can favor their antimicrobial resistance. These biofilm-forming bacteria produce a compact and protective matrix, allowing their adherence and colonization to different surfaces, and contributing to resistance, recurrence, and chronicity of the infections. Therefore, different therapeutic alternatives have been investigated to interrupt both cellular communication routes and biofilm formation. Among these, essential oils (EO) from Lippia origanoides thymol-carvacrol II chemotype (LOTC II) plants have demonstrated biological activity against different biofilm-forming pathogenic bacteria. In this work, we determined the effect of LOTC II EO on the expression of genes associated with quorum sensing (QS) communication, biofilm formation, and virulence of E. coli ATCC 25922 and S. aureus ATCC 29213. This EO was found to have high efficacy against biofilm formation, decreasing—by negative regulation—the expression of genes involved in motility (fimH), adherence and cellular aggregation (csgD), and exopolysaccharide production (pgaC) in E. coli. In addition, this effect was also determined in S. aureus where the L. origanoides EO diminished the expression of genes involved in QS communication (agrA), production of exopolysaccharides by PIA/PNG (icaA), synthesis of alpha hemolysin (hla), transcriptional regulators of the production of extracellular toxins (RNA III), QS and biofilm formation transcriptional regulators (sarA) and global regulators of biofilm formation (rbf and aur). Positive regulation was observed on the expression of genes encoding inhibitors of biofilm formation (e.g., sdiA and ariR). These findings suggest that LOTCII EO can affect biological pathways associated with QS communication, biofilm formation, and virulence of E. coli and S. aureus at subinhibitory concentrations and could be a promising candidate as a natural antibacterial alternative to conventional antibiotics. Full article
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14 pages, 7400 KiB  
Article
Lysine Inhibits Hemolytic Activity of Staphylococcus aureus and Its Application in Food Model Contaminated with Staphylococcus aureus
by Yangli Wan, Xiaowen Wang, Tianyi Bai, Xuting Zheng, Liu Yang, Qianhong Li and Xin Wang
Toxins 2022, 14(12), 867; https://doi.org/10.3390/toxins14120867 - 9 Dec 2022
Cited by 8 | Viewed by 3008
Abstract
Alpha-hemolysin (Hla) is one of the important exotoxins of Staphylococcus aureus (S. aureus) and can be used as a target to reduce the virulence of S. aureus. This study explored the inhibitory effect of Lysine (Lys) on Hla and its application [...] Read more.
Alpha-hemolysin (Hla) is one of the important exotoxins of Staphylococcus aureus (S. aureus) and can be used as a target to reduce the virulence of S. aureus. This study explored the inhibitory effect of Lysine (Lys) on Hla and its application in food safety. Lys significantly inhibited the expression of Hla at sub-inhibitory concentrations and directly interacted with Hla to interfere with its oligomerization and thus significantly inhibited its hemolytic activity. Notably, Lys attenuated S. aureus damage to mouse small intestine and Caco-2 cells and delayed mouse mortality. In the food model, Lys inhibited the expression of Hla of S. aureus and had no significant effect on the sensory score. Moreover, Lys had no obvious damage effect on the main organs of mice, which indicated that Lys has good biocompatibility and has the potential to be used in the food industry as an anti-S. aureus preparation. Full article
(This article belongs to the Special Issue Foodborne Toxins: Advanced Detection and Toxicity)
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8 pages, 1057 KiB  
Article
Staphylococcus aureus Alpha-Toxin in Deep Tracheal Aspirates—Preliminary Evidence for Its Presence in the Lungs of Sepsis Patients
by Sabine Ziesemer, Sven-Olaf Kuhn, Anke Hahnenkamp, Manuela Gerber, Elvira Lutjanov, Matthias Gruendling and Jan-Peter Hildebrandt
Toxins 2022, 14(7), 450; https://doi.org/10.3390/toxins14070450 - 30 Jun 2022
Cited by 1 | Viewed by 2774
Abstract
The pore forming alpha-toxin (hemolysin A, Hla) of Staphylococcus aureus (S. aureus) is a major virulence factor with relevance for the pathogenicity of this bacterium, which is involved in many cases of pneumonia and sepsis in humans. Until now, the presence [...] Read more.
The pore forming alpha-toxin (hemolysin A, Hla) of Staphylococcus aureus (S. aureus) is a major virulence factor with relevance for the pathogenicity of this bacterium, which is involved in many cases of pneumonia and sepsis in humans. Until now, the presence of Hla in the body fluids of potentially infected humans could only be shown indirectly, e.g., by the presence of antibodies against Hla in serum samples or by hemolysis testing on blood agar plates of bacterial culture supernatants of the clinical isolates. In addition, nothing was known about the concentrations of Hla actually reached in the body fluids of the infected hosts. Western blot analyses on 36 samples of deep tracheal aspirates (DTA) isolated from 22 hospitalized sepsis patients using primary antibodies against different epitopes of the Hla molecule resulted in the identification of six samples from five patients containing monomeric Hla (approx. 33 kDa). Two of these samples showed also signals at the molecular mass of heptameric Hla (232 kDa). Semiquantitative analyses of the samples revealed that the concentrations of monomeric Hla ranged from 16 to 3200 ng/mL. This is, to our knowledge, the first study directly showing the presence of S. aureus Hla in samples of airway surface liquid in human patients. Full article
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21 pages, 17721 KiB  
Review
Platelets, Bacterial Adhesins and the Pneumococcus
by Kristin Jahn, Thomas P. Kohler, Lena-Sophie Swiatek, Sergej Wiebe and Sven Hammerschmidt
Cells 2022, 11(7), 1121; https://doi.org/10.3390/cells11071121 - 25 Mar 2022
Cited by 17 | Viewed by 5786
Abstract
Systemic infections with pathogenic or facultative pathogenic bacteria are associated with activation and aggregation of platelets leading to thrombocytopenia and activation of the clotting system. Bacterial proteins leading to platelet activation and aggregation have been identified, and while platelet receptors are recognized, induced [...] Read more.
Systemic infections with pathogenic or facultative pathogenic bacteria are associated with activation and aggregation of platelets leading to thrombocytopenia and activation of the clotting system. Bacterial proteins leading to platelet activation and aggregation have been identified, and while platelet receptors are recognized, induced signal transduction cascades are still often unknown. In addition to proteinaceous adhesins, pathogenic bacteria such as Staphylococcus aureus and Streptococcus pneumoniae also produce toxins such as pneumolysin and alpha-hemolysin. They bind to cellular receptors or form pores, which can result in disturbance of physiological functions of platelets. Here, we discuss the bacteria-platelet interplay in the context of adhesin–receptor interactions and platelet-activating bacterial proteins, with a main emphasis on S. aureus and S. pneumoniae. More importantly, we summarize recent findings of how S. aureus toxins and the pore-forming toxin pneumolysin of S. pneumoniae interfere with platelet function. Finally, the relevance of platelet dysfunction due to killing by toxins and potential treatment interventions protecting platelets against cell death are summarized. Full article
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13 pages, 2674 KiB  
Article
In Silico Prediction and Design of Uropathogenic Escherichia coli Alpha-Hemolysin Generate a Soluble and Hemolytic Recombinant Toxin
by Bruna De Lucca Caetano, Marta de Oliveira Domingos, Miriam Aparecida da Silva, Jessika Cristina Alves da Silva, Juliana Moutinho Polatto, Fabio Montoni, Leo Kei Iwai, Daniel Carvalho Pimenta, Hugo Vigerelli, Paulo Cesar Gomes Vieira, Rita de Cassia Ruiz, José Salvatore Patané and Roxane Maria Fontes Piazza
Microorganisms 2022, 10(1), 172; https://doi.org/10.3390/microorganisms10010172 - 14 Jan 2022
Cited by 1 | Viewed by 3358
Abstract
The secretion of α-hemolysin by uropathogenic Escherichia coli (UPEC) is commonly associated with the severity of urinary tract infections, which makes it a predictor of poor prognosis among patients. Accordingly, this toxin has become a target for diagnostic tests and therapeutic interventions. However, [...] Read more.
The secretion of α-hemolysin by uropathogenic Escherichia coli (UPEC) is commonly associated with the severity of urinary tract infections, which makes it a predictor of poor prognosis among patients. Accordingly, this toxin has become a target for diagnostic tests and therapeutic interventions. However, there are several obstacles associated with the process of α-hemolysin purification, therefore limiting its utilization in scientific investigations. In order to overcome the problems associated with α-hemolysin expression, after in silico prediction, a 20.48 kDa soluble α-hemolysin recombinant denoted rHlyA was constructed. This recombinant is composed by a 182 amino acid sequence localized in the aa542–723 region of the toxin molecule. The antigenic determinants of the rHlyA were estimated by bioinformatics analysis taking into consideration the tertiary form of the toxin, epitope analysis tools, and solubility inference. The results indicated that rHlyA has three antigenic domains localized in the aa555–565, aa600–610, and aa674–717 regions. Functional investigation of rHlyA demonstrated that it has hemolytic activity against sheep red cells, but no cytotoxic effect against epithelial bladder cells. In summary, the results obtained in this study indicate that rHlyA is a soluble recombinant protein that can be used as a tool in studies that aim to understand the mechanisms involved in the hemolytic and cytotoxic activities of α-hemolysin produced by UPEC. In addition, rHlyA can be applied to generate monoclonal and/or polyclonal antibodies that can be utilized in the development of diagnostic tests and therapeutic interventions. Full article
(This article belongs to the Section Molecular Microbiology and Immunology)
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12 pages, 3717 KiB  
Article
Suppressing Alpha-Hemolysin as Potential Target to Screen of Flavonoids to Combat Bacterial Coinfection
by Shangwen He, Qian Deng, Bingbing Liang, Feike Yu, Xiaohan Yu, Dawei Guo, Xiaoye Liu and Hong Dong
Molecules 2021, 26(24), 7577; https://doi.org/10.3390/molecules26247577 - 14 Dec 2021
Cited by 12 | Viewed by 3493
Abstract
The rapid emergence of bacterial coinfection caused by cytosolic bacteria has become a huge threat to public health worldwide. Past efforts have been devoted to discover the broad-spectrum antibiotics, while the emergence of antibiotic resistance encourages the development of antibacterial agents. In essence, [...] Read more.
The rapid emergence of bacterial coinfection caused by cytosolic bacteria has become a huge threat to public health worldwide. Past efforts have been devoted to discover the broad-spectrum antibiotics, while the emergence of antibiotic resistance encourages the development of antibacterial agents. In essence, bacterial virulence is a factor in antibiotic tolerance. However, the discovery and development of new antibacterial drugs and special antitoxin drugs is much more difficult in the antibiotic resistance era. Herein, we hypothesize that antitoxin hemolytic activity can serve as a screening principle to select antibacterial drugs to combat coinfection from natural products. Being the most abundant natural drug of plant origins, flavonoids were selected to assess the ability of antibacterial coinfections in this paper. Firstly, we note that four flavonoids, namely, baicalin, catechin, kaempferol, and quercetin, have previously exhibited antibacterial abilities. Then, we found that baicalin, kaempferol, and quercetin have better inhibitions of hemolytic activity of Hla than catechin. In addition, kaempferol and quercetin, have therapeutic effectivity for the coinfections of Staphylococcus aureus and Pseudomonas aeruginosa in vitro and in vivo. Finally, our results indicated that kaempferol and quercetin therapied the bacterial coinfection by inhibiting S. aureus α-hemolysin (Hla) and reduced the host inflammatory response. These results suggest that antitoxins may play a promising role as a potential target for screening flavonoids to combat bacterial coinfection. Full article
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17 pages, 3483 KiB  
Article
Solution Structures of Bacillus anthracis Protective Antigen Proteins Using Small Angle Neutron Scattering and Protective Antigen 63 Ion Channel Formation Kinetics
by Ariel Michelman-Ribeiro, Kenneth A. Rubinson, Vitalii Silin and John J. Kasianowicz
Toxins 2021, 13(12), 888; https://doi.org/10.3390/toxins13120888 - 11 Dec 2021
Cited by 2 | Viewed by 3730
Abstract
We are studying the structures of bacterial toxins that form ion channels and enable macromolecule transport across membranes. For example, the crystal structure of the Staphylococcus aureus α-hemolysin (α-HL) channel in its functional state was confirmed using neutron reflectometry (NR) with the protein [...] Read more.
We are studying the structures of bacterial toxins that form ion channels and enable macromolecule transport across membranes. For example, the crystal structure of the Staphylococcus aureus α-hemolysin (α-HL) channel in its functional state was confirmed using neutron reflectometry (NR) with the protein reconstituted in membranes tethered to a solid support. This method, which provides sub-nanometer structural information, could also test putative structures of the Bacillus anthracis protective antigen 63 (PA63) channel, locate where B. anthracis lethal factor and edema factor toxins (LF and EF, respectively) bind to it, and determine how certain small molecules can inhibit the interaction of LF and EF with the channel. We report here the solution structures of channel-forming PA63 and its precursor PA83 (which does not form channels) obtained with small angle neutron scattering. At near neutral pH, PA83 is a monomer and PA63 a heptamer. The latter is compared to two cryo-electron microscopy structures. We also show that although the α-HL and PA63 channels have similar structural features, unlike α-HL, PA63 channel formation in lipid bilayer membranes ceases within minutes of protein addition, which currently precludes the use of NR for elucidating the interactions between PA63, LF, EF, and potential therapeutic agents. Full article
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18 pages, 1417 KiB  
Article
Genome Analysis of the Janthinobacterium sp. Strain SLB01 from the Diseased Sponge of the Lubomirskia baicalensis
by Sergei I. Belikov, Ivan S. Petrushin and Lubov I. Chernogor
Curr. Issues Mol. Biol. 2021, 43(3), 2220-2237; https://doi.org/10.3390/cimb43030156 - 11 Dec 2021
Cited by 4 | Viewed by 3731
Abstract
The strain Janthinobacterium sp. SLB01 was isolated from the diseased freshwater sponge Lubomirskia baicalensis (Pallas, 1776) and the draft genome was published previously. The aim of this work is to analyze the genome of the Janthinobacterium sp. SLB01 to search for pathogenicity factors [...] Read more.
The strain Janthinobacterium sp. SLB01 was isolated from the diseased freshwater sponge Lubomirskia baicalensis (Pallas, 1776) and the draft genome was published previously. The aim of this work is to analyze the genome of the Janthinobacterium sp. SLB01 to search for pathogenicity factors for Baikal sponges. We performed genomic analysis to determine virulence factors, comparing the genome of the strain SLB01 with genomes of other related J. lividum strains from the environment. The strain Janthinobacterium sp. SLB01 contained genes encoding violacein, alpha-amylases, phospholipases, chitinases, collagenases, hemolysin, and a type VI secretion system. In addition, the presence of conservative clusters of genes for the biosynthesis of secondary metabolites of tropodithietic acid and marinocine was found. We present genes for antibiotic resistance, including five genes encoding various lactamases and eight genes for penicillin-binding proteins, which are conserved in all analyzed strains. Major differences were found between the Janthinobacterium sp. SLB01 and J. lividum strains in the spectra of genes for glycosyltransferases and glycoside hydrolases, serine hydrolases, and trypsin-like peptidase, as well as some TonB-dependent siderophore receptors. Thus, the study of the analysis of the genome of the strain SLB01 allows us to conclude that the strain may be one of the pathogens of freshwater sponges. Full article
(This article belongs to the Section Molecular Microbiology)
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13 pages, 935 KiB  
Article
First Report of Antimicrobial Susceptibility and Virulence Gene Characterization Associated with Staphylococcus aureus Carriage in Healthy Camels from Tunisia
by Faten Ben Chehida, Haythem Gharsa, Wafa Tombari, Rachid Selmi, Sana Khaldi, Monia Daaloul, Karim Ben Slama and Lilia Messadi
Animals 2021, 11(9), 2754; https://doi.org/10.3390/ani11092754 - 21 Sep 2021
Cited by 8 | Viewed by 3460
Abstract
A total of 318 nasal and rectal swabs were collected from 159 apparently healthy camels (Camelus dromedarius) randomly selected from five regions in southern and central Tunisia and screened for Staphylococcus aureus carriage. Staphylococcus spp. were recovered from 152 of 159 [...] Read more.
A total of 318 nasal and rectal swabs were collected from 159 apparently healthy camels (Camelus dromedarius) randomly selected from five regions in southern and central Tunisia and screened for Staphylococcus aureus carriage. Staphylococcus spp. were recovered from 152 of 159 camels studied (95.6%) and in total 258 swabs (81%) were positive. Among these isolates, 16 were coagulase positive Staphylococcus (CoPS) (6.2%) and were characterized by biochemical and molecular tests as S. aureus. These were isolated from 14 camels (8.8%) with co-carriage in nasal and rectal mucosa by two camels. All S. aureus isolates recovered were methicillin-susceptible Staphylococcus aureus (MSSA) and were characterized by spa typing and PFGE. Three different spa types were recovered: t729, t4013 and a spa type newly registered as t19687, which was the most common. PFGE analysis revealed seven different patterns and these were characterized by MLST, which revealed five different sequence types (ST6, ST88, ST3583 and two new sequences, ST6504 and ST6506). All isolates harbored different virulence genes, including hld, encoding delta hemolysin; lukE–lukD, encoding bicomponent leukotoxin LukE–LukD; the clfB gene, encoding clumping factor B; the laminin gene, encoding laminin-binding protein; and cap8, encoding capsule type 8. Fifteen isolates harbored hemolysin beta (hlb) and fourteen encoded hemolysin alpha (hla) and hemolysin G2 (hlgv). Adhesin factors, including clfA and fnbB, were detected in five and four isolates respectively. Binding proteins, including collagen (cbp) and elastin-binding protein (ebp), were detected in two S. aureus isolates while fibrinogen-binding protein (fib) was identified in four isolates. This study provides the first set of genotyping data on the population structure and presence of toxin genes of S. aureus strains in Tunisian camels. Full article
(This article belongs to the Special Issue Trends in Camel Health and Production)
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13 pages, 1664 KiB  
Article
Within-Host Adaptation of Staphylococcus aureus in a Bovine Mastitis Infection Is Associated with Increased Cytotoxicity
by Katharina Mayer, Martin Kucklick, Helene Marbach, Monika Ehling-Schulz, Susanne Engelmann and Tom Grunert
Int. J. Mol. Sci. 2021, 22(16), 8840; https://doi.org/10.3390/ijms22168840 - 17 Aug 2021
Cited by 7 | Viewed by 2830
Abstract
Within-host adaptation is a typical feature of chronic, persistent Staphylococcus aureus infections. Research projects addressing adaptive changes due to bacterial in-host evolution increase our understanding of the pathogen’s strategies to survive and persist for a long time in various hosts such as human [...] Read more.
Within-host adaptation is a typical feature of chronic, persistent Staphylococcus aureus infections. Research projects addressing adaptive changes due to bacterial in-host evolution increase our understanding of the pathogen’s strategies to survive and persist for a long time in various hosts such as human and bovine. In this study, we investigated the adaptive processes of S. aureus during chronic, persistent bovine mastitis using a previously isolated isogenic strain pair from a dairy cow with chronic, subclinical mastitis, in which the last variant (host-adapted, Sigma factor SigB-deficient) quickly replaced the initial, dominant variant. The strain pair was cultivated under specific in vitro infection-relevant growth-limiting conditions (iron-depleted RPMI under oxygen limitation). We used a combinatory approach of surfaceomics, molecular spectroscopic fingerprinting and in vitro phenotypic assays. Cellular cytotoxicity assays using red blood cells and bovine mammary epithelial cells (MAC-T) revealed changes towards a more cytotoxic phenotype in the host-adapted isolate with an increased alpha-hemolysin (α-toxin) secretion, suggesting an improved capacity to penetrate and disseminate the udder tissue. Our results foster the hypothesis that within-host evolved SigB-deficiency favours extracellular persistence in S. aureus infections. Here, we provide new insights into one possible adaptive strategy employed by S. aureus during chronic, bovine mastitis, and we emphasise the need to analyse genotype–phenotype associations under different infection-relevant growth conditions. Full article
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