DOCSLIB.ORG

Clostridium Perfringens Vaccine

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Clostridium Perfringens Vaccine Europaisches Patentamt (19) European Patent Office Office europeeneen des brevets EP 0 892 054 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) |nt C|.6: C12N 15/31, A61 K 39/08, 20.01.1999 Bulletin 1999/03 C07K 1 4/33, C1 2N 1/21 (21) Application number: 98202032.3 (22) Date of filing: 17.06.1998 (84) Designated Contracting States: • Waterfield, Nicolas Robin AT BE CH CY DE DK ES Fl FR GB GR IE IT LI LU Cherry Hinton, Cambridge CB1 4YR (GB) MC NL PT SE • Frandsen, Peer Lyng Designated Extension States: 2840 Holte (DK) AL LT LV MK RO SI • Wells, Jeremy Mark Fen Ditton, Cambridge CB5 8ST (GB) (30) Priority: 20.06.1997 EP 97201888 (74) Representative: (71) Applicant: Akzo Nobel N.V. Ogilvie-Emanuelson, Claudia Maria et al 6824 BM Arnhem (NL) Patent Department Pharma N.V. Organon (72) Inventors: P.O. Box 20 • Sergers, Ruud Philip Antoon Maria 5340 BH Oss (NL) 5831 MZ Boxmeer (NL) (54) Clostridium perfringens vaccine (57) The present invention relates to detoxified im- genes encoding such p-toxins, as well as to expression munogenic derivatives of Clostridium perfringens p-tox- systems expressing such p-toxins. Moreover, the inven- in or an immunogenic fragment thereof that have as a tion relates to bacterial expression systems expressing characteristic that they carry a mutation in the p-toxin a native p-toxin. Finally, the invention relates to vaccines amino acid sequence, not found in the wild-type p-toxin based upon detoxified immunogenic derivatives of amino acid sequence. The invention also relates to Clostridium perfringens p-toxin, and methods for the preparation of such vaccines. < o CM O) 00 o a. LU Printed by Jouve, 75001 PARIS (FR) EP 0 892 054 A1 Description The present invention refers to detoxified immunogenic derivatives of Clostridium perfringens p-toxin, DNA en- coding such derivatives, Clostridium perfringens bacteria comprising DNA encoding such derivatives, Grampositive 5 bacterial expression systems comprising DNA encoding such derivatives, non-Clostridium perfringens-based Gram- positive bacterial expression systems expressing wild-type p-toxin, vaccines for combating Clostridium perfringens based thereon, methods for the preparation of native Clostridium perfringens p-toxin, methods for the preparation of detoxified immunogenic derivatives of Clostridium perfringens p-toxin and to methods for the preparation of vaccines for combating Clostridium perfringens. Clostridium perfringens (also known as C. welchii) is a species of the large 10 genus Clostridium. All bacteria belonging to this genus are spore-forming anaerobic Grampositive bacilli. The species C. perfringens can be subdivided in subspecies. Five subspecies have been described. These subspecies are generally known as "type" A-E. All subspecies produce several toxins, both major and minor toxins. The four major toxins are the a, p, e and x toxin. All C. perfringens types produce the a-toxin. The p-toxin is produced by C. perfringens types B and C. In addition, a range of minor toxins is produced by all C. perfringens types It is mainly due to the presence of is one or more of these various toxins in the five C. perfringens types, that all C. perfringens species are pathogenic. Type A is known to be pathogenic for both man and pigs. Type B is mainly pathogenic for lamb, sheep and goat, and causes "lamb dysenteria" and haemorragic enteritis. Type C is pathogenic for man, sheep, calf, lamb, pig, and bird. It is the cause of "struck1, haemorragic enteritis, necrotic enteritis and enterotoxemia. As mentioned above, both C. perfringens type B and type C are known to produce the p-toxin. The p-toxin is known 20 to play the major role in the pathogenesis of necrotic enteritis in both man and animal. In man, this disease has been termed pigbel (Johnson et al.: Lancet ii: 496-500, (1987)). In animals, necrotic enteritis has been described in calves, lambs and pigs (Hauschild, A.H.W. in S. Kadis, T.C.Montie, (ed.) Microbial toxins, p. 159-188. Academic press, Inc, New York (1971) and Willis, T.A. Anaerobic bacteriology: clinical and laboratory practice, 3rd ed. Butterworths, London (1977). 25 The p-toxin from Clostridium perfringens has been isolated in pure form (Sakurai et al., Infect. & Immun. 1 8: 741 -745 (1977), Sakurai et al., Toxicon 25: 1301-1310 (1987)). Much is still unknown about the biophysical properties of the toxin and thus about its mode of action. Due however to the fact that it could be obtained in a purified form the toxicity of p-toxin could be clearly demonstrated in animals. The lethal toxicity of purified p-toxin for e.g. mice and guinea-pigs was shown by Sakurai et al. (Infect. & Immun. 21: 678-680 (1978), Sakurai et al., Toxicon 25: 1301-1310 (1987)). 30 Recently, the nucleic acid sequence of the Clostridium perfringens p-toxin has been elucidated by Hunter et al. (Infect. & Immun. 61 : 3958-3965 (1 993)). The nucleic acid sequence revealed the size of the p-toxin protein to be about 35 kD. Due to the fact that the role of Clostridium perfringens p-toxin from type B and C in pathogenesis is of such paramount importance, much effort has been put in the development of immunity against this toxin. Immunity against the p-toxin is sufficient to protect against Clostridium perfringens type B and type C infection. The only way of inducing immunity 35 against the p-toxin is, to administer the toxin to the animal to be protected. It is however obvious that the toxin must be given in a detoxified form, since otherwise administration would lead to severe illness or death of the animal to be vaccinated. Vaccines based on detoxified p-toxin, also called p-toxoid, were available already around 1960 (e.g. G.B.Pat. No. 901 ,433, and U.S.Pat. No 3,288,680). 40 All currently available vaccines based on inactivated Clostridium perfringens p-toxin have however several important drawbacks. In the first place, all p-toxin-based vaccines comprise chemically detoxified, mainly formalin-detoxified, p-toxin and it was shown through the years that it is very difficult to standardise these chemical detoxification processes. The classical chemical methods for detoxification of proteins have the disadvantage that they alter the overall structure of the protein 45 in a fairly random manner. And as a result, during the process of chemical detoxification the immunogenic properties of the p-toxin also rapidly decrease. This can be seen e.g. from graph 1 and 2: in graph 2 it is shown, that at least 1% formalin, a very commonly used inactivation-compound, is necessary to detoxify the p-toxin under certain standard conditions. From graph 1 and 2, it can be seen however, that the antigenicity titre decreases dramatically with an 50 55 2 EP 0 892 054 A1 formalin vs titre 100 1 — — !■- ' — f- 70 f r P 10 75 Jf- 20 3% 2% 1% 0,5% 0,25% %formalin 25 • 30 Mg/ml - 6 Mg/ml • 1 .2 |jg/ml 0.24 pg/ml Graph 1 30 35 40 45 50 55 3 EP 0 892 054 A1 % dead animals in the groups 100 sa 80 CO E E 60 CO "O CD 20 0 3% 2% 1% 0,5% 0,25% formalin % I 30 Mg/ml 6 Mg/ml 1.2 Mg/ml ^VJ 0.24 Mg/ml Graph 2 increasing amount of formalin. A full titre can not be obtained anyway, because even the lowest amount of formalin needed for detoxification (graph 2) already gives a decrease of the titre. This implicates that there is only a very narrow band, in which both detoxification and a reasonable titre and thus immunogenicity can be obtained. Given this very narrow band, and the fact that there are at least three variables; time of detoxification, temperature and precise formalin- concentration, it is clear that it is very difficult to reproducibly produce detoxified p-toxin. Another approach for the detoxification of p-toxin is therefore highly wanted. No acceptable alternative has been found until now, for the following reason: the delicate balance between a sufficient level of detoxification and remaining immunogenicity implicates a close link between, on the one hand, the structure of the protein and, on the other hand, the biological properties of the protein. It could therefore not be expected to be possible to change the protein structure thereby detoxifying the protein, without at the same time significantly impairing the immunogenic characteristics of the protein. It is one of the merits of the present invention that it discloses for the first time a way to avoid the above-mentioned problem: using genetical manipulation techniques, specific and relatively large amino acid regions were surprisingly found, that can be mutated to provide the desired non-toxic derivatives of p-toxin without significantly impairing its necessary immunogenic properties. Thus, in one embodiment, the invention relates to detoxified immunogenic derivatives of Clostridium perfringens P-toxin or an immunogenic fragment thereof, carrying at least one mutation in its amino acid sequence, not found in wild-type p-toxin. An immunogenic fragment thereof is understood to be a fragment that, although not comprising the full length amino acid sequence of the derivative of the p-toxin, still comprises those regions of the derivative that are capable of inducing a protective immune response in the host animal. A mutation is understood to be a change in the amino acid sequence of the derivative p-toxin in comparison to the amino acid sequence of the wild-type p-toxin. The mutation is a substitution, deletion, insertion or inversion, or a combination thereof.
Load more

Recommended publications
  • Genome and Pangenome Analysis of Lactobacillus Hilgardii FLUB—A New Strain Isolated from Mead
    International Journal of Molecular Sciences Article Genome and Pangenome Analysis of Lactobacillus hilgardii FLUB—A New Strain Isolated from Mead Klaudia Gustaw 1,* , Piotr Koper 2,* , Magdalena Polak-Berecka 1 , Kamila Rachwał 1, Katarzyna Skrzypczak 3 and Adam Wa´sko 1 1 Department of Biotechnology, Microbiology and Human Nutrition, Faculty of Food Science and Biotechnology, University of Life Sciences in Lublin, Skromna 8, 20-704 Lublin, Poland; [email protected] (M.P.-B.); [email protected] (K.R.); [email protected] (A.W.) 2 Department of Genetics and Microbiology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland 3 Department of Fruits, Vegetables and Mushrooms Technology, Faculty of Food Science and Biotechnology, University of Life Sciences in Lublin, Skromna 8, 20-704 Lublin, Poland; [email protected] * Correspondence: [email protected] (K.G.); [email protected] (P.K.) Abstract: The production of mead holds great value for the Polish liquor industry, which is why the bacterium that spoils mead has become an object of concern and scientific interest. This article describes, for the first time, Lactobacillus hilgardii FLUB newly isolated from mead, as a mead spoilage bacteria. Whole genome sequencing of L. hilgardii FLUB revealed a 3 Mbp chromosome and five plasmids, which is the largest reported genome of this species. An extensive phylogenetic analysis and digital DNA-DNA hybridization confirmed the membership of the strain in the L. hilgardii species. The genome of L. hilgardii FLUB encodes 3043 genes, 2871 of which are protein coding sequences, Citation: Gustaw, K.; Koper, P.; 79 code for RNA, and 93 are pseudogenes.
    [Show full text]
  • Bioinformatics Resource Centers Systems Biology (Brcs) Centers
    Fondation Merieux – J Craig Venter Institute Bioinformatics Workshop December 5 – 8, 2017 Module 3: Genomic Data & Sequence Annotations in Public Databases NIH/NIAID Genomics and Bioinformatics Program SlideSource:A.S.Fauci SlideSource:A.S.Fauci Conducts and supports basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. NIAIDGenomicsProgram Proteomics Systems Sequencing Functional Structural Biology Genomics Genomics Genomic Clinical Functional Systems Sequencing Proteomics Structural Genomic Biology Centers Centers Genomics Research Centers Centers Centers Bioinformatics BioinformaticsResource Centers GenomicResearchResources Genomic/OmicsDataSets,Databases,BioinformaticsTools,Biomarkers,3DStructures,ProteinClones,PredictiveModels Toaddresskeyquestionsin microbiologyandinfectious disease NIAID Genome Sequencing Center Influenza Genome Sequencing Project at JCVI • 2004: 80 influenza genomes in GenBank • 3OCT2017: ~20,000 influenza genomes sequenced at JCVI • 75% complete influenza genomes in GenBank by JCVI Slide source: Maria Giovanni * Genome Sequencing Centers Bioinformatics Resource Centers Systems Biology (BRCs) Centers Structure Genomics Centers Clinical Proteomics Centers Courtesy of Alison Yao, DMID *Bioinformatics Resource Centers (BRCs) Goal: Provide integrated bioinformatics resources in support of basic and applied infectious diseases research • Data and metadata management and integration solutions • Computational analysis and visualization tools • Work
    [Show full text]
  • Metabolic and Genetic Basis for Auxotrophies in Gram-Negative Species
    Metabolic and genetic basis for auxotrophies in Gram-negative species Yara Seifa,1 , Kumari Sonal Choudharya,1 , Ying Hefnera, Amitesh Ananda , Laurence Yanga,b , and Bernhard O. Palssona,c,2 aSystems Biology Research Group, Department of Bioengineering, University of California San Diego, CA 92122; bDepartment of Chemical Engineering, Queen’s University, Kingston, ON K7L 3N6, Canada; and cNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, Denmark Edited by Ralph R. Isberg, Tufts University School of Medicine, Boston, MA, and approved February 5, 2020 (received for review June 18, 2019) Auxotrophies constrain the interactions of bacteria with their exist in most free-living microorganisms, indicating that they rely environment, but are often difficult to identify. Here, we develop on cross-feeding (25). However, it has been demonstrated that an algorithm (AuxoFind) using genome-scale metabolic recon- amino acid auxotrophies are predicted incorrectly as a result struction to predict auxotrophies and apply it to a series of the insufficient number of known gene paralogs (26). Addi- of available genome sequences of over 1,300 Gram-negative tionally, these methods rely on the identification of pathway strains. We identify 54 auxotrophs, along with the corre- completeness, with a 50% cutoff used to determine auxotrophy sponding metabolic and genetic basis, using a pangenome (25). A mechanistic approach is expected to be more appropriate approach, and highlight auxotrophies conferring a fitness advan- and can be achieved using genome-scale models of metabolism tage in vivo. We show that the metabolic basis of auxotro- (GEMs). For example, requirements can arise by means of a sin- phy is species-dependent and varies with 1) pathway structure, gle deleterious mutation in a conditionally essential gene (CEG), 2) enzyme promiscuity, and 3) network redundancy.
    [Show full text]
  • Insights Into the Phylogeny and Evolution of Cold Shock Proteins: from Enteropathogenic Yersinia and Escherichia Coli to Eubacteria
    International Journal of Molecular Sciences Article Insights into the Phylogeny and Evolution of Cold Shock Proteins: From Enteropathogenic Yersinia and Escherichia coli to Eubacteria Tao Yu 1,2,* , Riikka Keto-Timonen 2 , Xiaojie Jiang 2, Jussa-Pekka Virtanen 2 and Hannu Korkeala 2 1 Department of Life Science and Technology, Xinxiang University, Xinxiang 453003, China 2 Department of Food Hygiene and Environmental Health, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland * Correspondence: yu.tao@helsinki.fi Received: 21 July 2019; Accepted: 16 August 2019; Published: 20 August 2019 Abstract: Psychrotrophic foodborne pathogens, such as enteropathogenic Yersinia, which are able to survive and multiply at low temperatures, require cold shock proteins (Csps). The Csp superfamily consists of a diverse group of homologous proteins, which have been found throughout the eubacteria. They are related to cold shock tolerance and other cellular processes. Csps are mainly named following the convention of those in Escherichia coli. However, the nomenclature of certain Csps reflects neither their sequences nor functions, which can be confusing. Here, we performed phylogenetic analyses on Csp sequences in psychrotrophic enteropathogenic Yersinia and E. coli. We found that representative Csps in enteropathogenic Yersinia and E. coli can be clustered into six phylogenetic groups. When we extended the analysis to cover Enterobacteriales, the same major groups formed. Moreover, we investigated the evolutionary and structural relationships and the origin time of Csp superfamily members in eubacteria using nucleotide-level comparisons. Csps in eubacteria were classified into five clades and 12 subclades. The most recent common ancestor of Csp genes was estimated to have existed 3585 million years ago, indicating that Csps have been important since the beginning of evolution and have enabled bacterial growth in unfavorable conditions.
    [Show full text]
  • Yersiniabase: a Genomic Resource and Analysis Platform for Comparative Analysis of Yersinia
    Tan SY, Dutta A, Jakubovics NS, Ang MY, Siow CC, Mutha NV, Heydari H, Wee WY, Wong GJ, Choo SW. YersiniaBase: a genomic resource and analysis platform for comparative analysis of Yersinia. BMC Bioinformatics 2015, 16: 9. Copyright: © 2015 Tan et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. DOI link to article: http://dx.doi.org/10.1186/s12859-014-0422-y Date deposited: 25/11/2015 This work is licensed under a Creative Commons Attribution 4.0 International License Newcastle University ePrints - eprint.ncl.ac.uk Tan et al. BMC Bioinformatics (2015) 16:9 DOI 10.1186/s12859-014-0422-y DATABASE Open Access YersiniaBase: a genomic resource and analysis platform for comparative analysis of Yersinia Shi Yang Tan1,2, Avirup Dutta1, Nicholas S Jakubovics3, Mia Yang Ang1,2, Cheuk Chuen Siow1, Naresh VR Mutha1, Hamed Heydari1,4, Wei Yee Wee1,2, Guat Jah Wong1,2 and Siew Woh Choo1,2* Abstract Background: Yersinia is a Gram-negative bacteria that includes serious pathogens such as the Yersinia pestis,which causes plague, Yersinia pseudotuberculosis, Yersinia enterocolitica. The remaining species are generally considered non-pathogenic to humans, although there is evidence that at least some of these species can cause occasional infections using distinct mechanisms from the more pathogenic species.
    [Show full text]
  • Development of Listeriabase and Comparative Analysis of Listeria Monocytogenes Mui Fern Tan University of Malaya, Kuala Lumpur
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln CSE Journal Articles Computer Science and Engineering, Department of 2015 Development of ListeriaBase and comparative analysis of Listeria monocytogenes Mui Fern Tan University of Malaya, Kuala Lumpur Cheuk Chuen Siow University of Malaya, Kuala Lumpur Avirup Dutta University of Malaya, Kuala Lumpur Naresh VR Mutha University of Malaya, Kuala Lumpur Wei Yee Wee University of Malaya, Kuala Lumpur See next page for additional authors Follow this and additional works at: http://digitalcommons.unl.edu/csearticles Tan, Mui Fern; Siow, Cheuk Chuen; Dutta, Avirup; Mutha, Naresh VR; Wee, Wei Yee; Heydari, Hamed; Tan, Shi Yang; Ang, Mia Yang; Wong, Guat Jah; and Choo, Siew Woh, "Development of ListeriaBase and comparative analysis of Listeria monocytogenes" (2015). CSE Journal Articles. 127. http://digitalcommons.unl.edu/csearticles/127 This Article is brought to you for free and open access by the Computer Science and Engineering, Department of at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in CSE Journal Articles by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Authors Mui Fern Tan, Cheuk Chuen Siow, Avirup Dutta, Naresh VR Mutha, Wei Yee Wee, Hamed Heydari, Shi Yang Tan, Mia Yang Ang, Guat Jah Wong, and Siew Woh Choo This article is available at DigitalCommons@University of Nebraska - Lincoln: http://digitalcommons.unl.edu/csearticles/127 Tan et al. BMC Genomics (2015) 16:755 DOI 10.1186/s12864-015-1959-5 DATABASE Open Access Development of ListeriaBase and comparative analysis of Listeria monocytogenes Mui Fern Tan1,2†, Cheuk Chuen Siow1†, Avirup Dutta1, Naresh VR Mutha1, Wei Yee Wee1,2, Hamed Heydari1,4, Shi Yang Tan1,2, Mia Yang Ang1,2, Guat Jah Wong1,2 and Siew Woh Choo1,2,3* Abstract Background: Listeria consists of both pathogenic and non-pathogenic species.
    [Show full text]
  • RNA-Based Control of the Expression of the Type III Secretion System of Yersinia Pseudotuberculosis
    RNA-based control of the expression of the type III secretion system of Yersinia pseudotuberculosis Von der Fakultät für Lebenswissenschaften der Technischen Universität Carolo-Wilhelmina zu Braunschweig zur Erlangung des Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) genehmigte D i s s e r t a t i o n von Jörn Hoßmann aus Bützow 1. Referentin: Professorin Dr. Petra Dersch 2. Referent: Professor Dr. Michael Steinert eingereicht am: 22.02.2017 mündliche Prüfung (Disputation) am: 29.06.2017 Druckjahr 2018 Vorveröffentlichungen der Dissertation Teilergebnisse aus dieser Arbeit wurden mit Genehmigung der Fakultät für Lebenswissenschaften, vertreten durch die Mentorin der Arbeit, in folgenden Beiträgen vorab veröffentlicht: Publikationen Maurer CK, Fruth M, Empting M, Avrutina O, Hoßmann J, Nadmid S, Gorges J, Hermann J, Kazmeier U, Dersch P, Müller R and Hartmann RW: Discovery of the first small-molecule CsrA-RNA interaction inhibitors using biophysical screening technologies. Future Med. Chem. 8, 931–47 (2016). Posterbeiträge Hoßmann J, Pimenova M, Steinmann R, Opitz W, Heroven AK, Dersch P: Thermal and secretion-dependent regulation of the master regulator LcrF in Yersinia pseudotuberculosis. (Poster). 4th National Yersinia Meeting, Hamburg (2014). Hoßmann J, Pimenova M, Steinmann R, Opitz W, Heroven AK, Dersch P: Thermal and secretion-dependent regulation of the master regulator LcrF in Yersinia pseudotuberculosis. (Poster). Sensory and regulatory RNAs of procaryotes meeting, Braunschweig (2015). Hoßmann J, Pimenova M, Steinmann R, Opitz W, Heroven AK, Dersch P: Thermal and secretion-dependent regulation of the master regulator LcrF in Yersinia pseudotuberculosis. (Poster). 32nd Annual Meeting of NSCMID, Umea (2015). Table of contents Table of contents Table of contents ...................................................................................................I List of figures .....................................................................................................
    [Show full text]
  • Identification of Pathogenic Islands Using Comparative Genomics Based Tools
    Identification of Pathogenic Islands using Comparative Genomics Based Tools Author’s Note Every year I take my bioscience students on a field trip to the University of Florida’s campus in Gainesville. The students tour research labs, talk with graduate students, and get to perform a laboratory experiment on campus. It is the highlight of their year! During our field trip in November of 2012, we happened to have some down time between activities. I had noticed a flyer for an open lecture titled “From tRNA to protein modification: Linking gene function by comparative genomics” by Dr. Valérie de Crécy-Lagard. I didn’t know how much my students or myself would get out of it, but we went for it. It was there that I first met Valérie, an insanely energetic woman with enough enthusiasm about her research topic to fill an ocean. As a teacher, I recognized that comparative genomics and bioinformatics would be important to my students who chose to continue their education in the field of bioscience. My educational experience with CPET had provided me with a superficial background knowledge of comparative genomics and its importance as a research tool. During the lecture, Valérie mentioned a workshop that she was giving over the summer and afterwards I approached her for more information. She was more than happy to chat about it and told me I could email her. So I did. The response I got stated that the course was intensive and they were not sure I had the ‘necessary training in biochemistry and bioinformatics to participate’.
    [Show full text]
  • Identification of a Novel Yersinia Enterocolitica Strain from Bats in Association with a Bat Die-Off That Occurred in Georgia
    microorganisms Article Identification of a Novel Yersinia enterocolitica Strain from Bats in Association with a Bat Die-Off That Occurred in Georgia (Caucasus) 1,2, 3, 1 1 1 Tata Imnadze y, Ioseb Natradze y, Ekaterine Zhgenti , Lile Malania , Natalia Abazashvili , Ketevan Sidamonidze 1, Ekaterine Khmaladze 1, Mariam Zakalashvili 1, Paata Imnadze 1,2, Ryan J. Arner 4, Vladimir Motin 5 and Michael Kosoy 6,* 1 Lugar Center for Public Health Research, 0184 Tbilisi, Georgia; [email protected] (T.I.); [email protected] (E.Z.); [email protected] (L.M.); [email protected] (N.A.); [email protected] (K.S.); [email protected] (E.K.); [email protected] (M.Z.); [email protected] (P.I.) 2 Faculty of Medicine, Public Health and Epidemiology Department, Ivane Javakhishvili Tbilisi State University, 0179 Tbilisi, Georgia 3 Vertebrate Animals Research Group, Institute of Zoology, Ilia State University, 0162 Tbilisi, Georgia; [email protected] 4 Ryan Arner Science Consulting LLC, Freeport, PA 16229, USA; [email protected] 5 Department of Pathology, University Texas Medical Branch, Galveston, TX 77555-1019, USA; [email protected] 6 KB One Health LLC, Fort Collins, CO 80523, USA * Correspondence: [email protected] These authors contributed equally to this work. y Received: 11 June 2020; Accepted: 1 July 2020; Published: 4 July 2020 Abstract: Yersinia entercolitica is a bacterial species within the genus Yersinia, mostly known as a human enteric pathogen, but also recognized as a zoonotic agent widespread in domestic pigs. Findings of this bacterium in wild animals are very limited. The current report presents results of the identification of cultures of Y.
    [Show full text]
  • I DISSERTATION the SURFACE PROTEOME
    DISSERTATION THE SURFACE PROTEOME OF FRANCISELLA TULARENSIS Submitted by Jeffrey Craig Chandler Department of Microbiology, Immunology and Pathology In partial fulfillment of the requirements For the Degree of Doctor of Philosophy Colorado State University Fort Collins, Colorado Summer 2011 Doctoral Committee: Advisor: John T. Belisle Robert D. Gilmore Lawrence D. Goodridge Jeannine M. Petersen i ABSTRACT THE SURFACE PROTEOME OF FRANCISELLA TULARENSIS The surface associated lipids, polysaccharides, and proteins of bacterial pathogens often have significant roles in environmental and host-pathogen interactions. Lipopolysaccharide and an O-antigen polysaccharide capsule are the best defined Francisella tularensis surface molecules, and are important virulence factors that also contribute to the phenotypic variability of Francisella species, subspecies, and populations. In contrast, little is known regarding the composition and contributions of surface proteins in the biology of Francisella, or what roles they have in the documented phenotypic variability of this genus. A sufficient understanding of the Francisella surface proteome has been hampered by the few surface proteins identified and the inherent difficulty of characterizing new surface proteins. Thus, the objective of this dissertation was to provide an enhanced definition of F. tularensis surface proteome and evaluate how surface proteins relate to aspects of F. tularensis physiology, specifically humoral immunity and phenotypic variability of subspecies and populations. Analyses of the F. tularensis live vaccine strain surface proteome resulted in the identification of 36 proteins, 28 of which were newly described to the surface of this bacterium. Bioinformatic comparisons of surface proteins to their homologs in other Francisella species, subspecies, and populations revealed numerous differences that may contribute variable phenotypes, including significant alterations in the ChiA chitinase (FTL_1521).
    [Show full text]
  • The Genomic Characterisation and Comparison of Bacillus Cereus Strains Isolated from Indoor Air Balakrishnan N
    Premkrishnan et al. Gut Pathog (2021) 13:6 https://doi.org/10.1186/s13099-021-00399-4 Gut Pathogens GENOME REPORT Open Access The genomic characterisation and comparison of Bacillus cereus strains isolated from indoor air Balakrishnan N. V. Premkrishnan1†, Cassie E. Heinle1†, Akira Uchida1, Rikky W. Purbojati1, Kavita K. Kushwaha1, Alexander Putra1, Puramadathil Sasi Santhi1, Benjamin W. Y. Khoo1, Anthony Wong1, Vineeth Kodengil Vettath1, Daniela I. Drautz‑Moses1, Ana Carolina M. Junqueira2*† and Stephan C. Schuster1*† Abstract Background: Bacillus cereus is ubiquitous in nature, found in environments such as soil, plants, air, and part of the insect and human gut microbiome. The ability to produce endospores and bioflms contribute to their pathogenicity, classifed in two types of food poisoning: diarrheal and emetic syndromes. Here we report gap‑free, whole‑genome sequences of two B. cereus strains isolated from air samples and analyse their emetic and diarrheal potential. Results: Genome assemblies of the B. cereus strains consist of one chromosome and seven plasmids each. The genome size of strain SGAir0260 is 6.30‑Mb with 6590 predicted coding sequences (CDS) and strain SGAir0263 is 6.47‑ Mb with 6811 predicted CDS. Macrosynteny analysis showed 99% collinearity between the strains isolated from air and 90.2% with the reference genome. Comparative genomics with 57 complete B. cereus genomes suggests these strains from air are closely associated with strains isolated from foodborne illnesses outbreaks. Due to virulence poten‑ tial of B. cereus and its reported involvement in nosocomial infections, antibiotic resistance analyses were performed and confrmed resistance to ampicillin and fosfomycin, with susceptibility to ciprofoxacin, tetracycline and vancomy‑ cin in both strains.
    [Show full text]
  • Genome Sequencing and Analysis of the First Spontaneous Nanosilver 4 Resistant Bacterium Proteus Mirabilis Strain SCDR1
    bioRxiv preprint doi: https://doi.org/10.1101/089961; this version posted November 27, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Running Title: Nanosilver resistant Proteus mirabilis 2 3 Genome sequencing and analysis of the first spontaneous Nanosilver 4 resistant bacterium Proteus mirabilis strain SCDR1 5 6 Amr T. M. Saeb 1*, Khalid A. Al-Rubeaan1, Mohamed Abouelhoda 2, 3, Manojkumar Selvaraju 3, 4, and 7 Hamsa T. Tayeb 2, 3 8 9 1. Genetics and Biotechnology Department, Strategic Center for Diabetes Research, College of 10 medicine, King Saud University, KSA. 11 2. Genetics Department, King Faisal Specialist Hospital and Research Center, Riyadh, KSA. 12 3. Saudi Human Genome Project, King Abdulaziz City for Science and Technology (KACST), 13 Riyadh, KSA 14 4. Integrated Gulf Biosystems, Riyadh, KSA. 15 5. Department of Pathology & Laboratory Medicine, King Faisal Specialist Hospital and Research 16 Center, Riyadh, KSA. 17 6. Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, KSA 18 19 20 21 22 23 24 *Corresponding Author: 25 Amr T. M. Saeb, Ph.D. 26 Genetics and Biotechnology Department, 27 Strategic Center for Diabetes Research, 28 College of medicine, King Saud University, KSA. 29 Tel: +966-566263979 30 Fax: +966-11-4725682 31 Email: [email protected] 32 bioRxiv preprint doi: https://doi.org/10.1101/089961; this version posted November 27, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]