Molecular Mechanisms of Streptococcus Pyogenes Tissue Colonization and Invasion Antonin Weckel

Total Page:16

File Type:pdf, Size:1020Kb

Molecular Mechanisms of Streptococcus Pyogenes Tissue Colonization and Invasion Antonin Weckel Molecular mechanisms of Streptococcus pyogenes tissue colonization and invasion Antonin Weckel To cite this version: Antonin Weckel. Molecular mechanisms of Streptococcus pyogenes tissue colonization and invasion. Microbiology and Parasitology. Université Sorbonne Paris Cité, 2018. English. NNT : 2018US- PCB097. tel-02984777 HAL Id: tel-02984777 https://tel.archives-ouvertes.fr/tel-02984777 Submitted on 1 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Université Paris Descartes Ecole doctorale BioSPC Institut Cochin INSERM U1016 / Equipe Barrières et Pathogènes Molecular mechanisms of Streptococcus pyogenes tissue colonization and invasion By Antonin WECKEL PhD Thesis in Microbiology Directed by Agnès Fouet Thesis defense: 30th of October 2018 Jury members: Pr Anna NORRBY-TEGLUND Reviewer Dr Pascale SERROR Reviewer Pr François VANDENESCH Examiner Dr Philippe BOUSSO Examiner Dr Agnès FOUET PhD supervisor “We have to remember that what we observe is not nature herself, but nature exposed to our method of questioning” Werner Heisenberg Physics and Philosophy: The Revolution in Modern Science (1958) Acknowledgements I would like to thank Pascale Serror, Anna Norrby-Teglund, François Vandenesch and Philippe Bousso for having kindly accepted to be part of my defense jury, in particular to Anna Norrby- Teglund who came from Sweden for my defense. It has been 12 years now that I realized I want to work in life science research. Considering the beginning of my memories, this is more than half of my life having this idea stuck in my head. I want here to take the time to acknowledge all the people who contributed to this seed to grow into the doctor I’m about to become: the beauty of a flower resides less in the seed than in the quality of the environment it is exposed to during its growth. I consider that over the past years, I have been enlightened and watered by being surrounded by many wonderful people. While this dissertation and PhD are mine, this work belongs also to all of them. Thanks to Agnès and Claire for accepting me in the team and project. Agnès was a wonderful supervisor, always here when I needed her. I learned so much with her; she was a very good GPS during my PhD, I never felt lost and her directions were always correct. A very kind, upright and mindful boss. Thanks to Claire for always being kind and frank with me. Céline Méhats. Officially my “collaborator”. We had such a friendly and productive collaboration. You put so much energy into this project that started from nothing. You are a wonderful researcher and I am so glad I had the chance to work with you. Thanks to Thomas Guilbert. He gave me the knowledge, the curiosity, the will to work in microscopy. I never ever did microscopy before I met him and I still remember his first “lesson” on the microscope. He replied to several calls while I was such in a state in the L2 microscope during my night experiments. 9pm, 10pm. He was in bars, restaurants. He shouldn’t have replied. But I am so glad he did!! Thanks to Thierry Meylheuc for the SEM images. I will never forget the excitement of the first session with you, discovering the beautiful landscape of the infection at the nanometric level. Thanks to Magalie for all the help and support at the beginning of my PhD. Thanks to Samuel for being my biochemistry mentor and such a friendly colleague. Thanks to Constantin, my last year roommate, labmate, late evening-mate, weekend-mate and dissertation-mate. I am glad we had the opportunity to do our last year together, working next to you made everything easier to go through. Thanks to all past and current members of my team. Abdel, Asmaa, Anne-Sophie, Céline, Clara, Gerald, Julie and Lionel. A very nice environment and people to work in and with. Thanks to all the interns I had the chance or not to supervise. You learn a lot from your own mistakes, but also from those of others. Special thanks to Dorian, Quentin and Sandra. Thanks to the Donnadieu team. I owe you a lot, I had so much help and so many advice from all of you. I would not have done a 100th of what I did in microscopy without you. You always welcomed me and tried to help. Thanks to Elisa, Vincent, Emmanuel, Alain, Sarah, Chahrazade. Thanks to my former teacher and supervisors (Mr Poisson, Marie-Claude Serre, David Ermert and Anna Blom). You trusted me, and gave me all the knowledge and tools to start my PhD in the most comfortable way possible. Thanks to the people from the facilities I used during this PhD: Cybio, Proteomic facility and the Imag’IC facility. Thanks to Maryline Bajolle for her kindness and help. Thanks to Méchain building, Florian, Gaëlle, Christophe, Marina, Mickaël, Roy, Maxence, Ghina, Fanny, and all the people at the Institute I’ve been working for a couple of years . 1 Thanks to JeCCo and associates, Armelle, Stéphane, Marion, Gabrielle, Gabriel, Simon, Robin, Cyril, Mariangela, Rozenn, Anaïs, Vincent, Milica. Thanks for all this time releasing pressure from our day work and from the beer tap. I always think of Coralie, Béatrice, Nicolas and David as a special category of friends. We did secondary school together. I know them for more than 10 years. Thanks for all the time spent together and for being friends I wish to keep all my life. Who could have guessed while taking our daily lunch in the Agora we would ever be here for my PhD! ENS was a great opportunity on many aspects. Meeting Pierre, Aurélien, Noémie, Anne, Justine, Thomas, Valentine, Milena, Julia, Ralitza and Xavier was one of the best. So many parties, so many holidays and memories altogether. So much fun. Thank you all. Thanks to Mickael and Alex. Thanks for making me speak English and drinking beer on a regular base. You are true friends that always helped me through time of doubts. I have two brothers and a sister, Adrien, Amélie and Louis. I am so glad we had the opportunity to spend monthly time together for several years in Paris when we were reunited. Though we are no longer on the same continent, I know I have a wonderful family I can count on at any time in my life and this is invaluable. Thanks to all the members of my family, for their care and love, especially my godmother Corinne. Thanks to my grandfather for saying since I knew I wanted to do research: “A researcher who searches, it is easy to find, but a researcher who finds, we are still searching for them”. To which I used to reply in my innocent and naive youth and with a sense of humor: “I will not become a researcher, but a finder”. My parents definitely played a critical role in my calling to science. Though none is a scientist, I have been nurtured on science very early in life, and I will never ever be able to thank them sufficiently for that. They gave me all I needed to develop my curiosity and to have the best education. They kindly supported all my life decisions. My prepa was a difficult time not only for me but also for them, they bore and tolerated things many parents would not have. It was a time none of us regret, but I don’t know if they realize that I would not have done it without them. They have always trusted me, more than I ever did, or ever will trust myself. The further I get from childhood, the further I am from their life, the harder it is for me to retain tears thinking of my own mother not sleeping for me to grow up in the most suitable environment. I don’t know if anything can be worth what they did for me, but I want to thank them and dedicate this PhD to them. So far I described many “categories” of people that helped me over the past years. Coralie enters all categories: she has always been here for me and for a long time, she cared for me, she was here at any time of the day and night for my tears and my laughs, she helped me a lot to release the pressure from the lab. You tolerated my bad mood and accepted that I come and leave our sweet home in the middle of the night, and the following days when I was tired and unpleasant. Thank you. We did it, together, hand in hand. 2 Remerciements J’aimerais remercier Pascale Serror, Anna Norrby-Teglund, François Vandenesch et Philippe Bousso d’avoir gentiment accepté de faire partie de mon jury de thèse. Merci en particulier à Anna Norrby-Teglund qui a fait le déplacement depuis la Suède. Cela fait maintenant 12 ans que j’ai réalisé que j’aimerais travailler dans la recherche en biologie. En prenant compte de l’âge de mes premiers souvenirs, j’ai eu cette idée coincée dans ma tête durant plus de la moitié de ma vie. J’aimerais ici prendre le temps de remercier toutes les personnes qui ont contribué à faire de cette graine le docteur que je suis sur le point de devenir : la beauté d’une fleur réside moins dans la graine que dans l’environnement auquel elle est exposée durant sa croissance.
Recommended publications
  • The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections
    toxins Review The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections Patience Shumba 1, Srikanth Mairpady Shambat 2 and Nikolai Siemens 1,* 1 Center for Functional Genomics of Microbes, Department of Molecular Genetics and Infection Biology, University of Greifswald, D-17489 Greifswald, Germany; [email protected] 2 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland; [email protected] * Correspondence: [email protected]; Tel.: +49-3834-420-5711 Received: 20 May 2019; Accepted: 10 June 2019; Published: 11 June 2019 Abstract: Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both Gram-positive bacteria secrete a variety of molecules, including pore-forming exotoxins, superantigens, and proteases with cytolytic and immunomodulatory functions. The present review summarizes the current knowledge about streptococcal and staphylococcal toxins in NSTIs with a special focus on their contribution to disease progression, tissue pathology, and immune evasion strategies. Keywords: Streptococcus pyogenes; group A streptococcus; Staphylococcus aureus; skin infections; necrotizing soft tissue infections; pore-forming toxins; superantigens; immunomodulatory proteases; immune responses Key Contribution: Group A streptococcal and Staphylococcus aureus toxins manipulate host physiological and immunological responses to promote disease severity and progression. 1. Introduction Necrotizing soft tissue infections (NSTIs) are rare and represent a more severe rapidly progressing form of soft tissue infections that account for significant morbidity and mortality [1].
    [Show full text]
  • Quercetin Inhibits Virulence Properties of Porphyromas Gingivalis In
    www.nature.com/scientificreports OPEN Quercetin inhibits virulence properties of Porphyromas gingivalis in periodontal disease Zhiyan He1,2,3,7, Xu Zhang1,2,3,7, Zhongchen Song2,3,4, Lu Li5, Haishuang Chang6, Shiliang Li5* & Wei Zhou1,2,3* Porphyromonas gingivalis is a causative agent in the onset and progression of periodontal disease. This study aims to investigate the efects of quercetin, a natural plant product, on P. gingivalis virulence properties including gingipain, haemagglutinin and bioflm formation. Antimicrobial efects and morphological changes of quercetin on P. gingivalis were detected. The efects of quercetin on gingipains activities and hemolytic, hemagglutination activities were evaluated using chromogenic peptides and sheep erythrocytes. The bioflm biomass and metabolism with diferent concentrations of quercetin were assessed by the crystal violet and MTT assay. The structures and thickness of the bioflms were observed by confocal laser scanning microscopy. Bacterial cell surface properties including cell surface hydrophobicity and aggregation were also evaluated. The mRNA expression of virulence and iron/heme utilization was assessed using real time-PCR. Quercetin exhibited antimicrobial efects and damaged the cell structure. Quercetin can inhibit gingipains, hemolytic, hemagglutination activities and bioflm formation at sub-MIC concentrations. Molecular docking analysis further indicated that quercetin can interact with gingipains. The bioflm became sparser and thinner after quercetin treatment. Quercetin also modulate cell surface hydrophobicity and aggregation. Expression of the genes tested was down-regulated in the presence of quercetin. In conclusion, our study demonstrated that quercetin inhibited various virulence factors of P. gingivalis. Periodontal disease is a common chronic infammatory disease that characterized swelling and bleeding of the gums clinically, and leading to the progressive destruction of tooth-supporting tissues including the gingiva, alveolar bone, periodontal ligament, and cementum.
    [Show full text]
  • Cysteine Proteinases of Microorganisms and Viruses
    ISSN 00062979, Biochemistry (Moscow), 2008, Vol. 73, No. 1, pp. 113. © Pleiades Publishing, Ltd., 2008. Original Russian Text © G. N. Rudenskaya, D. V. Pupov, 2008, published in Biokhimiya, 2008, Vol. 73, No. 1, pp. 317. REVIEW Cysteine Proteinases of Microorganisms and Viruses G. N. Rudenskaya1* and D. V. Pupov2 1Faculty of Chemistry and 2Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; fax: (495) 9393181; Email: [email protected] Received May 7, 2007 Revision received July 18, 2007 Abstract—This review considers properties of secreted cysteine proteinases of protozoa, bacteria, and viruses and presents information on the contemporary taxonomy of cysteine proteinases. Literature data on the structure and physicochemical and enzymatic properties of these enzymes are reviewed. High interest in cysteine proteinases is explained by the discovery of these enzymes mostly in pathogenic organisms. The role of the proteinases in pathogenesis of several severe diseases of human and animals is discussed. DOI: 10.1134/S000629790801001X Key words: cysteine proteinases, properties, protozoa, bacteria, viruses Classification and Catalytic Mechanism papain and related peptidases showed that the catalytic of Cysteine Proteinases residues are arranged in the following order in the polypeptide chain: Cys, His, and Asn. Also, a glutamine Cysteine proteinases are peptidyl hydrolases in residue preceding the catalytic cysteine is also important which the role of the nucleophilic group of the active site for catalysis. This residue is probably involved in the for is performed by the sulfhydryl group of a cysteine residue. mation of the oxyanion cavity of the enzyme. The cat Cysteine proteinases were first discovered and investigat alytic cysteine residue is usually followed by a residue of ed in tropic plants.
    [Show full text]
  • Molecular Mechanisms of Inhibition of Streptococcus Species by Phytochemicals
    molecules Review Molecular Mechanisms of Inhibition of Streptococcus Species by Phytochemicals Soheila Abachi 1, Song Lee 2 and H. P. Vasantha Rupasinghe 1,* 1 Faculty of Agriculture, Dalhousie University, Truro, NS PO Box 550, Canada; [email protected] 2 Faculty of Dentistry, Dalhousie University, Halifax, NS PO Box 15000, Canada; [email protected] * Correspondence: [email protected]; Tel.: +1-902-893-6623 Academic Editors: Maurizio Battino, Etsuo Niki and José L. Quiles Received: 7 January 2016 ; Accepted: 6 February 2016 ; Published: 17 February 2016 Abstract: This review paper summarizes the antibacterial effects of phytochemicals of various medicinal plants against pathogenic and cariogenic streptococcal species. The information suggests that these phytochemicals have potential as alternatives to the classical antibiotics currently used for the treatment of streptococcal infections. The phytochemicals demonstrate direct bactericidal or bacteriostatic effects, such as: (i) prevention of bacterial adherence to mucosal surfaces of the pharynx, skin, and teeth surface; (ii) inhibition of glycolytic enzymes and pH drop; (iii) reduction of biofilm and plaque formation; and (iv) cell surface hydrophobicity. Collectively, findings from numerous studies suggest that phytochemicals could be used as drugs for elimination of infections with minimal side effects. Keywords: streptococci; biofilm; adherence; phytochemical; quorum sensing; S. mutans; S. pyogenes; S. agalactiae; S. pneumoniae 1. Introduction The aim of this review is to summarize the current knowledge of the antimicrobial activity of naturally occurring molecules isolated from plants against Streptococcus species, focusing on their mechanisms of action. This review will highlight the phytochemicals that could be used as alternatives or enhancements to current antibiotic treatments for Streptococcus species.
    [Show full text]
  • Beta-Haemolytic Streptococci (BHS)
    technical sheet Beta-Haemolytic Streptococci (BHS) Classification Transmission Gram-positive cocci, often found in chains Transmission is generally via direct contact with nasopharyngeal secretions from ill or carrier animals. Family Animals may also be infected by exposure to ill or Streptococcaceae carrier caretakers. β-haemolytic streptococci are characterized by Lancefield grouping (a characterization based on Clinical Signs and Lesions carbohydrates in the cell walls). Only some Lancefield In mice and rats, generally none. Occasional groups are of clinical importance in laboratory rodents. outbreaks of disease associated with BHS are Streptococci are generally referred to by their Lancefield reported anecdotally and in the literature. In most grouping but genus and species are occasionally used. cases described, animals became systemically ill after experimental manipulation, and other animals Group A: Streptococcus pyogenes in the colony were found to be asymptomatic Group B: Streptococcus agalactiae carriers. In a case report not involving experimental Group C: Streptococcus equi subsp. zooepidemicus manipulation, DBA/2NTac mice and their hybrids were Group G: Streptococcus canis more susceptible to an ascending pyelonephritis and subsequent systemic disease induced by Group B Affected species streptococci than other strains housed in the same β-haemolytic streptococci are generally considered barrier. opportunists that can colonize most species. Mice and guinea pigs are reported most frequently with clinical In guinea pigs, infection with Group C streptococci signs, although many rodent colonies are colonized leads to swelling and infection of the lymph nodes. with no morbidity, suggesting disease occurs only with Guinea pigs can be inapparent carriers of the organism severe stress or in other exceptional circumstances.
    [Show full text]
  • The Microbiology of Impetigo in Indigenous Children: Associations Between Streptococcus Pyogenes, Staphylococcus Aureus, Scabies
    Bowen et al. BMC Infectious Diseases DOI 10.1186/s12879-014-0727-5 RESEARCH ARTICLE Open Access The microbiology of impetigo in Indigenous children: associations between Streptococcus pyogenes, Staphylococcus aureus, scabies, and nasal carriage Asha C Bowen1,2,3*, Steven YC Tong1,4, Mark D Chatfield3 and Jonathan R Carapetis2,3 Abstract Background: Impetigo is caused by both Streptococcus pyogenes and Staphylococcus aureus; the relative contributions of each have been reported to fluctuate with time and region. While S. aureus is reportedly on the increase in most industrialised settings, S. pyogenes is still thought to drive impetigo in endemic, tropical regions. However, few studies have utilised high quality microbiological culture methods to confirm this assumption. We report the prevalence and antimicrobial resistance of impetigo pathogens recovered in a randomised, controlled trial of impetigo treatment conducted in remote Indigenous communities of northern Australia. Methods: Each child had one or two sores, and the anterior nares, swabbed. All swabs were transported in skim milk tryptone glucose glycogen broth and frozen at –70°C, until plated on horse blood agar. S. aureus and S. pyogenes were confirmed with latex agglutination. Results: From 508 children, we collected 872 swabs of sores and 504 swabs from the anterior nares prior to commencement of antibiotic therapy. S. pyogenes and S. aureus were identified together in 503/872 (58%) of sores; with an additional 207/872 (24%) sores having S. pyogenes and 81/872 (9%) S. aureus, in isolation. Skin sore swabs taken during episodes with a concurrent diagnosis of scabies were more likely to culture S.
    [Show full text]
  • Characterization of Cathepsin L Genes and Their Cdnas in the Brine Shrimp, Artemia Franciscana
    University of Windsor Scholarship at UWindsor Electronic Theses and Dissertations Theses, Dissertations, and Major Papers 2006 Characterization of cathepsin L genes and their cDNAs in the brine shrimp, Artemia franciscana. Jian Ping Cao University of Windsor Follow this and additional works at: https://scholar.uwindsor.ca/etd Recommended Citation Cao, Jian Ping, "Characterization of cathepsin L genes and their cDNAs in the brine shrimp, Artemia franciscana." (2006). Electronic Theses and Dissertations. 1398. https://scholar.uwindsor.ca/etd/1398 This online database contains the full-text of PhD dissertations and Masters’ theses of University of Windsor students from 1954 forward. These documents are made available for personal study and research purposes only, in accordance with the Canadian Copyright Act and the Creative Commons license—CC BY-NC-ND (Attribution, Non-Commercial, No Derivative Works). Under this license, works must always be attributed to the copyright holder (original author), cannot be used for any commercial purposes, and may not be altered. Any other use would require the permission of the copyright holder. Students may inquire about withdrawing their dissertation and/or thesis from this database. For additional inquiries, please contact the repository administrator via email ([email protected]) or by telephone at 519-253-3000ext. 3208. CHARACTERIZATION OF CATHEPSIN L GENES AND THEIR cDNAs IN THE BRINE SHRIMP, ARTEMIA FRANCISCANA By: JianPing Cao A Thesis Submitted to the Faculty of Graduate Studies and Research through the Department of Biological Sciences in Partial Fulfillment of the Requirements for the Degree of Master of Science at the University of Windsor Windsor, Ontario, Canada 2006 Reproduced with permission of the copyright owner.
    [Show full text]
  • Porphyromonas Gingivalis Hmuy and Streptococcus Gordonii GAPDH—Novel Heme Acquisition Strategy in the Oral Microbiome
    International Journal of Molecular Sciences Article Porphyromonas gingivalis HmuY and Streptococcus gordonii GAPDH—Novel Heme Acquisition Strategy in the Oral Microbiome 1, 1, 2 1 Paulina Sl˛ezak´ y, Michał Smiga´ y , John W. Smalley , Klaudia Siemi ´nska and Teresa Olczak 1,* 1 Laboratory of Medical Biology, Faculty of Biotechnology, University of Wrocław, 14A F. Joliot-Curie St., 50-383 Wrocław, Poland; [email protected] (P.S.);´ [email protected] (M.S.);´ [email protected] (K.S.) 2 School of Dentistry, Institute of Clinical Sciences, University of Liverpool, Daulby St., Liverpool L69 3GN, UK; [email protected] * Correspondence: [email protected] These authors contributed equally to this study and share the first authorship. y Received: 18 May 2020; Accepted: 8 June 2020; Published: 10 June 2020 Abstract: The oral cavity of healthy individuals is inhabited by commensals, with species of Streptococcus being the most abundant and prevalent in sites not affected by periodontal diseases. The development of chronic periodontitis is linked with the environmental shift in the oral microbiome, leading to the domination of periodontopathogens. Structure-function studies showed that Streptococcus gordonii employs a “moonlighting” protein glyceraldehyde-3-phosphate dehydrogenase (SgGAPDH) to bind heme, thus forming a heme reservoir for exchange with other proteins. Secreted or surface-associated SgGAPDH coordinates Fe(III)heme using His43. Hemophore-like heme-binding proteins of Porphyromonas gingivalis (HmuY), Prevotella intermedia (PinO) and Tannerella forsythia (Tfo) sequester heme complexed to SgGAPDH. Co-culturing of P. gingivalis with S. gordonii results in increased hmuY gene expression, indicating that HmuY might be required for efficient inter-bacterial interactions.
    [Show full text]
  • Carriage Profile of Transient Oral Bacteria Among Dar Es Salaam Hypertensive Patients and Its Association to Hypertension
    Arch Microbiol Immunology 2019; 3 (3): 094-101 DOI: 10.26502/ami.93650033 Research Article Carriage Profile of Transient Oral Bacteria among Dar es Salaam Hypertensive Patients and its Association to Hypertension Boaz Cairo, George Msema Bwire*, Kennedy Daniel Mwambete Department of Pharmaceutical Microbiology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Box 65001, Dar es Salaam, Tanzania *Corresponding Author: George Msema Bwire, Department of Pharmaceutical Microbiology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Box 65001, Dar es Salaam, Tanzania, E-mail: [email protected] Received: 03 July 2019; Accepted: 05 August 2019; Published: 07 August 2019 Abstract Background: The causes of hypertension can be either reversible and/or irreversible. Oral infections caused by transient normal flora, Porphyromonas gingivalis in particular is among the reversible factors which can directly or indirectly influence hypertension. Therefore, the study was conducted to determine the oral bacterial profile and establish an association between P. gingivalis carriage and hypertension.. Methods: A hospital based cross sectional study was conducted between January and July 2018 at Muhimbili National Hospital, Dar es Salaam. Oral swabs were collected and cultured in the appropriate media for isolation of bacteria. Bacterial identification was done using cultural properties and series of biochemical tests. Cramer’s V test analyzed categorical variables while Pearson correlation analyzed continous variables. Logistic regression was used in determination of Odds Ratio (OR). P value less than 0.05 was considered statistically significant. Results: In 120 hypertensive patients (HTP) the most isolated bacterial species were Streptococcus pyogenes, Streptococcus agalactiae and Staphylococcus aureus by 20.6%, 18.8%and 7.1% respectively while for 50 non- hypertensive patients (NHTP) were 9.4%, 8.2% and 2.9% for S.
    [Show full text]
  • Inactivation of Streptococcus Pyogenes Extracellular Cysteine Protease Significantly Decreases Mouse Lethality of Serotype M3 and M49 Strains
    Inactivation of Streptococcus pyogenes extracellular cysteine protease significantly decreases mouse lethality of serotype M3 and M49 strains. S Lukomski, … , A Podbielski, J M Musser J Clin Invest. 1997;99(11):2574-2580. https://doi.org/10.1172/JCI119445. Research Article Cysteine proteases have been implicated as important virulence factors in a wide range of prokaryotic and eukaryotic pathogens, but little direct evidence has been presented to support this notion. Virtually all strains of the human bacterial pathogen Streptococcus pyogenes express a highly conserved extracellular cysteine protease known as streptococcal pyrogenic exotoxin B (SpeB). Two sets of isogenic strains deficient in SpeB cysteine protease activity were constructed by integrational mutagenesis using nonreplicating recombinant plasmids containing a truncated segment of the speB gene. Immunoblot analyses and enzyme assays confirmed that the mutant derivatives were deficient in expression of enzymatically active SpeB cysteine protease. To test the hypothesis that the cysteine protease participates in host mortality, we assessed the ability of serotype M3 and M49 wild-type strains and isogenic protease-negative mutants to cause death in outbred mice after intraperitoneal inoculation. Compared to wild-type parental organisms, the serotype M3 speB mutant lost virtually all ability to cause mouse death (P < 0.00001), and similarly, the virulence of the M49 mutant was detrimentally altered (P < 0.005). The data unambiguously demonstrate that the streptococcal enzyme is a virulence factor, and thereby provide additional evidence that microbial cysteine proteases are critical in host-pathogen interactions. Find the latest version: https://jci.me/119445/pdf Rapid Publication Inactivation of Streptococcus pyogenes Extracellular Cysteine Protease Significantly Decreases Mouse Lethality of Serotype M3 and M49 Strains Slawomir Lukomski,* Srinand Sreevatsan,* Cornelia Amberg,‡ Werner Reichardt,‡ Markus Woischnik,§ Andreas Podbielski,§ and James M.
    [Show full text]
  • Proteolytic Enzymes in Grass Pollen and Their Relationship to Allergenic Proteins
    Proteolytic Enzymes in Grass Pollen and their Relationship to Allergenic Proteins By Rohit G. Saldanha A thesis submitted in fulfilment of the requirements for the degree of Masters by Research Faculty of Medicine The University of New South Wales March 2005 TABLE OF CONTENTS TABLE OF CONTENTS 1 LIST OF FIGURES 6 LIST OF TABLES 8 LIST OF TABLES 8 ABBREVIATIONS 8 ACKNOWLEDGEMENTS 11 PUBLISHED WORK FROM THIS THESIS 12 ABSTRACT 13 1. ASTHMA AND SENSITISATION IN ALLERGIC DISEASES 14 1.1 Defining Asthma and its Clinical Presentation 14 1.2 Inflammatory Responses in Asthma 15 1.2.1 The Early Phase Response 15 1.2.2 The Late Phase Reaction 16 1.3 Effects of Airway Inflammation 16 1.3.1 Respiratory Epithelium 16 1.3.2 Airway Remodelling 17 1.4 Classification of Asthma 18 1.4.1 Extrinsic Asthma 19 1.4.2 Intrinsic Asthma 19 1.5 Prevalence of Asthma 20 1.6 Immunological Sensitisation 22 1.7 Antigen Presentation and development of T cell Responses. 22 1.8 Factors Influencing T cell Activation Responses 25 1.8.1 Co-Stimulatory Interactions 25 1.8.2 Cognate Cellular Interactions 26 1.8.3 Soluble Pro-inflammatory Factors 26 1.9 Intracellular Signalling Mechanisms Regulating T cell Differentiation 30 2 POLLEN ALLERGENS AND THEIR RELATIONSHIP TO PROTEOLYTIC ENZYMES 33 1 2.1 The Role of Pollen Allergens in Asthma 33 2.2 Environmental Factors influencing Pollen Exposure 33 2.3 Classification of Pollen Sources 35 2.3.1 Taxonomy of Pollen Sources 35 2.3.2 Cross-Reactivity between different Pollen Allergens 40 2.4 Classification of Pollen Allergens 41 2.4.1
    [Show full text]
  • Streptococcosis Humans and Animals
    Zoonotic Importance Members of the genus Streptococcus cause mild to severe bacterial illnesses in Streptococcosis humans and animals. These organisms typically colonize one or more species as commensals, and can cause opportunistic infections in those hosts. However, they are not completely host-specific, and some animal-associated streptococci can be found occasionally in humans. Many zoonotic cases are sporadic, but organisms such as S. Last Updated: September 2020 equi subsp. zooepidemicus or a fish-associated strain of S. agalactiae have caused outbreaks, and S. suis, which is normally carried in pigs, has emerged as a significant agent of streptoccoccal meningitis, septicemia, toxic shock-like syndrome and other human illnesses, especially in parts of Asia. Streptococci with human reservoirs, such as S. pyogenes or S. pneumoniae, can likewise be transmitted occasionally to animals. These reverse zoonoses may cause human illness if an infected animal, such as a cow with an udder colonized by S. pyogenes, transmits the organism back to people. Occasionally, their presence in an animal may interfere with control efforts directed at humans. For instance, recurrent streptococcal pharyngitis in one family was cured only when the family dog, which was also colonized asymptomatically with S. pyogenes, was treated concurrently with all family members. Etiology There are several dozen recognized species in the genus Streptococcus, Gram positive cocci in the family Streptococcaceae. Almost all species of mammals and birds, as well as many poikilotherms, carry one or more species as commensals on skin or mucosa. These organisms can act as facultative pathogens, often in the carrier. Nomenclature and identification of streptococci Hemolytic reactions on blood agar and Lancefield groups are useful in distinguishing members of the genus Streptococcus.
    [Show full text]