DOCSLIB.ORG

Pathogenicity Islands: Minireview Bacterial Evolution in Quantum Leaps

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pathogenicity Islands: Minireview Bacterial Evolution in Quantum Leaps Cell, Vol. 87, 791±794, November 29, 1996, Copyright 1996 by Cell Press Pathogenicity Islands: Minireview Bacterial Evolution in Quantum Leaps Eduardo A. Groisman* and Howard Ochman² for the secretion of virulence proteins by Yersinia, Erwinia, *Department of Molecular Microbiology Pseudomonas, Xanthomonas, Shigella, and Salmonella Washington University School of Medicine (Van Gijsegem et al., 1993)Ðand these systems differ from St. Louis, Missouri 63110 the sec-dependent pathway in that their effector mole- ² Department of Biology cules lack a typical signal sequence. University of Rochester At the same location where LEE has inserted into entero- Rochester, New York 14627 pathogenic strains (McDaniel et al., 1995) a distinct patho- genicity island, PAI-1, has been identified in a uropatho- ªI am the beneficiary of a lucky break in the genetic genic strain of E. coli (Blum et al., 1994; Figure 1). Both sweepstakesº islands are targeted to the same basepair downstream of Isaac Asimov the selC gene, which codes for the selenocysteine-specific tRNA. LEE and PAI-1 contain different sets of genes: PAI-1 The Molecular Bases of Virulence is 70 kb in length and encodes a hemolysin. Thus, the For most bacterial pathogens virulence is a multifactorial specific cassette incorporated at the selC locus deter- process requiring two general classes of determinants. mines whether strains of E. coli are converted into entero- The first encompasses genes that participate in physiolog- or uropathogens. ical processes necessary for survival in host and non-host Aside from PAI-1 and LEE, three other pathogenicity environments, and these genes are generally found in both islands have been identified in E. coli (Figure 1); and, in pathogenic and non-pathogenicorganisms. In Salmonella, fact, certain uropathogenic strains contain more than one this set includes regulatory genes, such as phoP/phoQ, pathogenicity island. In addition to PAI-1, E. coli strain 536 that control expression of more than 20 loci in response also harbors a 190-kb pathogenicity island, PAI-2, that to low magnesium environments; biosynthetic genes, such has integrated at the tRNAleuX locus and contains genes as aroA, that encodes the ability to synthesize aromatic for an alternate hemolysin and Prf-type fimbriae (Blum et amino acids not found in host tissues; and several addi- al., 1994). The other pathogenicity islands detected in E. tional genes required for cell maintenance and DNA repair coli also contain hemolysin genes but are associated with (Groisman and Ochman, 1994). The second class of virulence genes specifies traits that are unique to pathogens, and, not surprisingly, these genes are rarely detected in non-pathogenic organisms. Based on the initial characterizations of plasmids from Yersinia and Shigella, such sequences were originally thought to be confined to extrachromosomal elements; but recently, several virulence cassettes have been mapped to the chromosome of pathogenic organisms. These segments of the chromosome, termed pathogenic- ity islands (Hacker et al., 1990; Lee, 1996; see Figure 1), can be of any length, but, most often, they accommodate large clusters of genes contributing a particular virulence phenotype. Pathogenicity islands have been recognized by their association with transmissible DNA, their sporadic distribution in a set of related pathogenic and non-patho- genic organisms, or the unusual features of their encoded genes, and their recent characterization has provided clues regarding their origins, distribution, mode of transfer, and genetic stability. Pathogenicity Islands Dictate Disease Condition Incorporation of a pathogenicity island can, in a single step, transform a normally benign organism into a patho- gen. For example, enteropathogenic E. coli contain a chro- mosomal segment that mediates attaching and effacing lesions on intestinal epithelial cells (McDaniel et al., 1995; Figure 1). This 35 kb regionÐtermed LEE for locus of en- terocyte effacementÐis absent from laboratory strains Figure 1. Location of Selected Pathogenicity Islands and Phages and codes for an outer membrane protein that promotes of Gram-Negative Bacteria contact with host cells and a type III secretion system that Chromosomes and pathogenicity islands are depicted as blue lines exports proteins known to modify host cell functions. Type and black triangles, respectively, and are not drawn to scale. The III secretion systems are prevalent among animal and plant presence of repeated sequences at the site of insertion, which is pathogensÐhomologous export systems are responsible shown below the island, is indicated by short yellow lines. Cell 792 different tRNA loci: the island at the pheV locus contains pathogen. The SPI-1 invasion island is present in represen- genes for P-fimbriae, which allow the pathogen to adhere tative strains from all subspecific groups of Salmonella, to cells lining the urinary tract, whereas the island at the although sporadic cases of secondary loss have been pheR locus codes for Prs fimbriae, which bind Gal Nac- reported for individual isolates of S. enterica sv. Seften- 1±3-Gal Nac±containing receptors rather the Gal-b-1±4- berg and Litchfield. But, in contrast to SPI-1, SPI-2- Gal residues recognized by the P fimbrial adhesins (Blum hybridizing sequences have not been detected in S. et al., 1995). In addition, the island at the pheR locus codes bongori (subspecies V), the most divergent lineage of for a type 1 cytotoxic necrotizing factor, which causes Salmonella. The incorporation of the SPI-1 and SPI-2 multinucleation and enlargement of eukaryotic cells and pathogenicity islands enabled Salmonella to invade host can trigger phagocytosis by epithelial cells (Falzano et al., cells, evade host defense systems, and cause systemic 1993). Sequences similar to those present in the pathoge- infections in mammals, while its close relative E. coli nicity islands of uropathogenic strains have been detected evolved as a commensal and opportunistic pathogen. in plasmids of hemolytic strains of E. coli, highlighting the On the other hand, the four nominal species of Shigella, mobile nature of these sequences. all of which emerged relatively recently from E. coli, Pathogenicity Islands Mediate Specific gained the ability to enter host cells following the acqui- Phases of the Infection Process sition of the large virulence plasmid, thereby becoming Two pathogenicity islands have been identified in Salmo- invasive pathogens of primates. nella, each contributing to a specific step in the course Gain and Loss of Pathogenicity Islands of infection. The island at 63', designated SPI-1 (Figure The occurrence of pathogenicity islands raises several 1), governs the ability of Salmonella to invade epithe- questions about the evolution of virulence in bacteria. lial cells (Mills et al., 1995; Gala n, 1996), and a second First, what advantage does the incorporation of viru- island at 31', designated SPI-2, mediates survival within lence genes into the chromosome provide over retaining macrophages (Ochman et al., 1996; Shea et al., 1996). them on episomes? Although many virulence determi- Both islands are 40 kb in length and appear to have nants occur on extrachromosomal DNAs, integration been acquired by horizontal gene transfer because their into the chromosome circumvents the need for autono- G1C contents are lower than those typical of Salmonella mously replicating elements. This also lowers the proba- (Groisman et al., 1993). bility that a given gene will be eliminated because epi- The nucleotide sequence of the SPI-1 island is nearly somes must be under continuous selective pressure to complete, and this region includes at least 25 genes, the be maintained whereas the spontaneous elimination of majority of which encode components of a Type III secre- chromosomal genes is not as high. However, plasmid tion system and its effector proteins (Gala n, 1996). The integration can result in the inactivation of chromosomal assemblage of genes specifying this export apparatus in loci or in the alteration of the expression of plasmid- Salmonella is similar in size, sequence, and organization encoded genes: for example, insertion of the Shigella to a set of genes in the Shigella virulence plasmid (Grois- flexneri virulence plasmid into the metB locus leads to man and Ochman, 1993), and several of the proteins en- methionine auxotrophy and decreased expression of coded by these gene clusters arecapable of cross-species the invasion proteins (Zagaglia et al., 1991). complementation. However, certain genes within the Sal- Second, how are pathogenicity islands incorporated monella invasion island, such as orgA and hil,haveno into the bacterial chromosome? Analysis of the junc- counterparts in the Shigella virulence plasmid and may be tions of pathogenicity islands can reveal the mechanism responsible for the differential regulation of invasion in used to integrate these sequences. As noted above, the Shigella and Salmonella: this property is controlled by genes encoded by PAI-1 and LEE of E. coli are clearly temperature in Shigella and by oxygen tension, osmolarity, different, but the site of insertion within the selC-tRNA and pH in Salmonella. The vast differences in G1C con- gene is conserved (McDaniel et al., 1995). This suggests tents and the phylogenetic distribution of the invasion that both islands were acquired by a similar mechanism gene clusters argue that Salmonella and Shigella gained which was likely to be phage-mediated since selC also these sequences
Load more

Recommended publications
  • Helicobacter Pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells
    Report Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells Graphical Abstract Authors Max Koeppel, Fernando Garcia-Alcalde, Frithjof Glowinski, Philipp Schlaermann, Thomas F. Meyer Correspondence [email protected] In Brief The gastric pathogen H. pylori can cause cancer in humans by compromising the genomic integrity of infected cells. Koeppel et al. show that infection affects the DNA damage response and reveal a DNA damage pattern reminiscent of genomic aberrations found in gastric tumors. Highlights Accession Numbers d H. pylori impairs the DNA repair response in normal human GSE55699 epithelial cells d Distinct genomic regions show increased susceptibility to H. pylori-induced damage d DNA damage accumulates in telomere-proximal, actively transcribed regions d Susceptible genomic regions overlap with gastric cancer genomic aberrations Koeppel et al., 2015, Cell Reports 11, 1703–1713 June 23, 2015 ª2015 The Authors http://dx.doi.org/10.1016/j.celrep.2015.05.030 Cell Reports Report Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells Max Koeppel,1 Fernando Garcia-Alcalde,1 Frithjof Glowinski,1 Philipp Schlaermann,1 and Thomas F. Meyer1,* 1Department of Molecular Biology, Max Planck Institute for Infection Biology, Charite´ platz 1, 10117 Berlin, Germany *Correspondence: [email protected] http://dx.doi.org/10.1016/j.celrep.2015.05.030 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). SUMMARY (Jenks et al., 2003; Touati et al., 2003). This process has been linked to reduced expression of mismatch repair genes (Kim Infection with the human pathogen Helicobacter et al., 2002) and increased expression of activation-induced cyti- pylori (H.
    [Show full text]
  • Analysis and Construction of Pathogenicity Island Regulatory Pathways in Salmonella Enterica Serovar Typhi
    Journal of Integrative Bioinformatics, 7(1):145, 2010 http://journal.imbio.de Analysis and construction of pathogenicity island regulatory pathways in Salmonella enterica serovar Typhi Su Yean Ong1 *, Fui Ling Ng1, Siti Suriawati Badai1, Anton Yuryev2, Maqsudul Alam1 1 Centre for Chemical Biology, Universiti Sains Malaysia, 1st Floor, Block B, No. 10, Persiaran Bukit Jambul, 11900 Bayan Lepas, Pulau Pinang, Malaysia 2 Ariadne Genomics Inc., 9430 Key West Avenue, Suite 113, Rockville, MD 20850, USA [email protected], [email protected], [email protected], [email protected], [email protected] Summary Signal transduction through protein-protein interactions and protein modifications are the main mechanisms controlling many biological processes. Here we described the (http://creativecommons.org/licenses/by-nc-nd/3.0/). implementation of MedScan information extraction technology and Pathway Studio software (Ariadne Genomics Inc.) to create a Salmonella specific molecular interaction License database. Using the database, we have constructed several signal transduction pathways in Salmonella enterica serovar Typhi which causes Typhoid Fever, a major health threat especially in developing countries. S. Typhi has several pathogenicity islands that control Unported rapid switching between different phenotypes including adhesion and colonization, 3.0 invasion, intracellular survival, proliferation, and biofilm formation in response to environmental changes. Understanding of the detailed mechanism for S. Typhi survival in host cells is necessary for development of efficient detection and treatment of this pathogen. The constructed pathways were validated using publically available gene expression microarray data for Salmonella. Bioinformatics. 1 Introduction Integrative S. Typhi is able to survive a variety of harsh conditions and defense mechanisms existing in of the human gastrointestinal tract.
    [Show full text]
  • Identification of a Pathogenicity Island, Which Contains Genes For
    Proc. Natl. Acad. Sci. USA Vol. 96, pp. 10875–10880, September 1999 Microbiology Identification of a pathogenicity island, which contains genes for virulence and avirulence, on a large native plasmid in the bean pathogen Pseudomonas syringae pathovar phaseolicola (plant disease resistance͞hypersensitive reaction͞signal transduction) ROBERT W. JACKSON*, EVANGELOS ATHANASSOPOULOS†‡,GEORGE TSIAMIS†‡,JOHN W. MANSFIELD†§,ANE SESMA¶, ʈ DAWN L. ARNOLD*, MARJORIE J. GIBBON*, JESUS MURILLO¶,JOHN D. TAYLOR , AND ALAN VIVIAN* *Department of Biological and Biomedical Sciences, University of the West of England, Coldharbor Lane, Bristol BS16 1QY, United Kingdom; †Department of Biological Sciences, Wye College, Wye, Ashford, Kent TN25 5AH, United Kingdom; ¶Escuela Te´cnica Superior de Ingenieros Agro´nomos, Universidad Pu´blica de Navarra, 31006 Pamplona, Spain; and ʈHorticulture Research International, Wellesbourne, Warwick CV35 9EF, United Kingdom Communicated by Noel T. Keen, University of California, Riverside, CA, July 7, 1999 (received for review April 2, 1999) ABSTRACT The 154-kb plasmid was cured from race 7 Certain avr genes, although recognized by their ability to strain 1449B of the phytopathogen Pseudomonas syringae pv. activate plant defenses (the HR), also may have a role in phaseolicola (Pph). Cured strains lost virulence toward bean, pathogenicity in the absence of the interacting R gene in the causing the hypersensitive reaction in previously susceptible host plant. In some cases there is a clear, qualitative effect on cultivars. Restoration of virulence was achieved by complemen- pathogenicity of mutations in avr genes, as with avrBs2 in tation with cosmid clones spanning a 30-kb region of the plasmid certain races of Xanthomonas campestris pv. vesicatoria in that contained previously identified avirulence (avr) genes avrD, pepper and avrRpm1 in P.
    [Show full text]
  • The Role of Integrating Conjugative Elements in Helicobacter Pylori: a Review Langgeng Agung Waskito1,2, Jeng Yih-Wu3 and Yoshio Yamaoka1,4,5*
    Waskito et al. Journal of Biomedical Science (2018) 25:86 https://doi.org/10.1186/s12929-018-0489-2 REVIEW Open Access The role of integrating conjugative elements in Helicobacter pylori: a review Langgeng Agung Waskito1,2, Jeng Yih-Wu3 and Yoshio Yamaoka1,4,5* Abstract The genome of Helicobacter pylori contains many putative genes, including a genetic region known as the Integrating Conjugative Elements of H. pylori type four secretion system (ICEHptfs). This genetic regions were originally termed as “plasticity zones/regions” due to the great genetic diversity between the original two H. pylori whole genome sequences. Upon analysis of additional genome sequences, the regions were reported to be extremely common within the genome of H. pylori. Moreover, these regions were also considered conserved rather than genetically plastic and were believed to act as mobile genetic elements transferred via conjugation. Although ICEHptfs(s) are highly conserved, these regions display great allele diversity, especially on ICEHptfs4, with three different subtypes: ICEHptfs4a, 4b, and 4c. ICEHptfs were also reported to contain a novel type 4 secretion system (T4SS) with both epidemiological and in vitro infection model studies highlighting that this novel T4SS functions primarily as a virulence factor. However, there is currently no information regarding the structure, the genes responsible for forming the T4SS, and the interaction between this T4SS and other virulence genes. Unlike the cag pathogenicity island (PAI), which contains CagA, a gene found to be essential for H. pylori virulence, these novel T4SSs have not yet been reported to contain genes that contribute significant effects to the entire system.
    [Show full text]
  • Cag, a Pathogenicity Island of Helicobacter Pylori, Encodes Type I
    Proc. Natl. Acad. Sci. USA Vol. 93, pp. 14648–14653, December 1996 Genetics cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors (secretionyinsertion sequenceyinflammationyevolution) STEFANO CENSINI,CHRISTINA LANGE,ZHAOYING XIANG*, JEAN E. CRABTREE†,PAOLO GHIARA, MARK BORODOVSKY‡,RINO RAPPUOLI, AND ANTONELLO COVACCI§ Immunobiological Research Institute of Siena, Chiron Vaccines, Via Fiorentina 1, 53100 Siena, Italy Communicated by Stanley Falkow, Stanford University School of Medicine, Stanford, CA, October 9, 1996 (received for review June 14, 1996) ABSTRACT cagA, a gene that codes for an immunodom- Genetic analysis shows that the cagA gene is present only in inant antigen, is present only in Helicobacter pylori strains that type I strains, while the vacA gene is present in both types (4). are associated with severe forms of gastroduodenal disease An active toxin is produced only by type I strains; however, the (type I strains). We found that the genetic locus that contains linkage between CagA and VacA expression is not yet clear cagA (cag) is part of a 40-kb DNA insertion that likely was since the cagA and vacA genes are located more than 300 kb acquired horizontally and integrated into the chromosomal apart on the chromosome of the H. pylori NCTC 11638 (11). glutamate racemase gene. This pathogenicity island is flanked Moreover, it has been shown that inactivation of the cagA gene by direct repeats of 31 bp. In some strains, cag is split into a has no consequence on expression of VacA or on the ability to right segment (cagI) and a left segment (cagII) by a novel induce IL-8 (12–14).
    [Show full text]
  • CAG PATHOGENICITY ISLAND of Helicobacter Pylori and ITS ASSOCIATION to PRENEOPLASTIC LESIONS and GASTRIC CANCER
    Artículo de Revisión Cristancho Liévano, F.; Trujillo Gama, E.; Bravo Hernández, M.M.: cagPAI Helicobacter pylori CAG PATHOGENICITY ISLAND OF Helicobacter pylori AND ITS ASSOCIATION TO PRENEOPLASTIC LESIONS AND GASTRIC CANCER EL ISLOTE DE PATOGENICIDAD CAG DE Helicobacter pylori Y SU ASOCIACIÓN CON LESIONES PRENEOPLÁSICAS Y CÁNCER GÁSTRICO Felipe Cristancho Liévano1, Esperanza Trujillo Gama2, María Mercedes Bravo Hernández3 1Biólogo, Grupo de Investigación en Biología del Cáncer. Instituto Nacional de Cancerología, Calle 1 No. 9-85, Bogotá, D.C., Colombia, e-mail: [email protected], https://orcid.org/0000-0002-2652-6372; 2Química, M.Sc., Grupo de Investi- gación en Biología del Cáncer. Instituto Nacional de Cancerología, Calle 1 No. 9-85, Bogotá, D.C., Colombia, e-mail: estrujil- [email protected]; 3Microbióloga, M.Sc., Grupo de Investigación en Biología del Cáncer. Instituto Nacional de Cancerología, Calle 1 No. 9-85, Bogotá, D.C., Colombia, e-mail: [email protected], https://orcid.org/0000-0002-6472-8362 Rev. U.D.C.A Act. & Div. Cient. 21(2): 309-318, Julio-Diciembre, 2018 https://doi.org/10.31910/rudca.v21.n2.2018.972 Open access article published by Revista U.D.C.A Actualidad & Divulgación Científica under a Creative Commons CC BY-NC 4.0 International License ABSTRACT población mundial. Los efectos patológicos ocasionados por la infección con H. pylori dependen, en buena parte, Gastric cancer is one of the main causes of death by cancer de un sistema de secreción tipo IV, codificado en el islote in the world and the infection with Helicobacter pylori is de patogenicidad cag (cagPAI).
    [Show full text]
  • Genome Sequencing and Analysis of Salmonella Enterica Subsp. Enterica Serovar Stanley UPM
    Genome sequencing and analysis of Salmonella enterica subsp. enterica serovar Stanley UPM 517: Insights on its virulence-associated elements and their potentials as vaccine candidates Khalidah Syahirah Ashari1, Najwa Syahirah Roslan2, Abdul Rahman Omar2,3, Mohd Hair Bejo2,3, Aini Ideris2,4 and Nurulfiza Mat Isa1,2 1 Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia 2 Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia 3 Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia 4 Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia ABSTRACT Salmonella enterica subsp. enterica serovar Stanley (S. Stanley) is a pathogen that contaminates food, and is related to Salmonella outbreaks in a variety of hosts such as humans and farm animals through products like dairy items and vegetables. Despite the fact that several vaccines of Salmonella strains had been constructed, none of them were developed according to serovar Stanley up to this day. This study presents results of genome sequencing and analysis on our S. Stanley UPM 517 strain taken from fecal swabs of 21-day-old healthy commercial chickens in Perak, Malaysia and used Salmonella enterica subsp. enterica serovar Typhimurium LT2 (S. Typhimurium LT2) as a reference to be compared with. First, sequencing and Submitted 2 August 2018 assembling of the Salmonella Stanley UPM 517 genome into a contiguous form were Accepted 5 April 2019 done. The work was then continued with scaffolding and gap filling. Annotation and Published 28 June 2019 alignment of the draft genome was performed with S.
    [Show full text]
  • An Analysis of Outer Inflammatory Protein a in Cag Pathogenicity Island Negative and Positive Strains of Helicobacter Pylori
    W&M ScholarWorks Undergraduate Honors Theses Theses, Dissertations, & Master Projects 4-2017 An Analysis of Outer Inflammatory Protein A in cag Pathogenicity Island Negative and Positive Strains of Helicobacter pylori Danielle N. Horridge College of William and Mary Follow this and additional works at: https://scholarworks.wm.edu/honorstheses Part of the Bacteriology Commons, and the Pathogenic Microbiology Commons Recommended Citation Horridge, Danielle N., "An Analysis of Outer Inflammatory Protein A in cag Pathogenicity Island Negative and Positive Strains of Helicobacter pylori" (2017). Undergraduate Honors Theses. Paper 1126. https://scholarworks.wm.edu/honorstheses/1126 This Honors Thesis is brought to you for free and open access by the Theses, Dissertations, & Master Projects at W&M ScholarWorks. It has been accepted for inclusion in Undergraduate Honors Theses by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. An Analysis of Outer Inflammatory Protein A in cag Pathogenicity Island Negative and Positive Strains of Helicobacter pylori Danielle N. Horridge1 1- The College of William & Mary, Williamsburg, VA 23187 A thesis submitted in partial fulfillment of the requirements of the degree of Bachelor of Science with Honors in Biology from The College of William & Mary in Virginia. Williamsburg, Virginia May 2017 © Copyright by Danielle N. Horridge 2017 Abstract OipA, outer inflammatory protein A, is an outer membrane protein virulence factor of the gastric pathogen Helicobacter pylori. oipA expression is regulated by phase variation at a CT dinucleotide repeat located within the 5’ end of the gene, such that the gene is alternatively in- frame (Phase On) or out-of-frame (Phase Off).
    [Show full text]
  • CRISPR-Based Screening of Genomic Island Excision Events in Bacteria
    CRISPR-based screening of genomic island excision events in bacteria Kurt Sellea,b, Todd R. Klaenhammera,b,1, and Rodolphe Barrangoua,1 aDepartment of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27695; and bFunctional Genomics Graduate Program, North Carolina State University, Raleigh, NC 27695 Contributed by Todd R. Klaenhammer, May 19, 2015 (sent for review September 22, 2014) Genomic analysis of Streptococcus thermophilus revealed that RNAs (crRNAs) that guide Cas proteins for sequence-specific mobile genetic elements (MGEs) likely contributed to gene acqui- recognition and cleavage of target DNA complementary to the sition and loss during evolutionary adaptation to milk. Clustered spacer (7). CRISPR-Cas technology has applications in strain regularly interspaced short palindromic repeats–CRISPR-associated typing and detection (8–10), exploitation of natural/engineered genes (CRISPR-Cas), the adaptive immune system in bacteria, limits immunity against mobile genetic elements (11), programmable genetic diversity by targeting MGEs including bacteriophages, genome editing in diverse backgrounds (12), transcriptional con- transposons, and plasmids. CRISPR-Cas systems are widespread trol (13, 14), and manipulation of microbial populations in defined in streptococci, suggesting that the interplay between CRISPR- consortia (15). Cas systems and MGEs is one of the driving forces governing Although sequence features corresponding to CRISPR arrays genome homeostasis in this genus. To investigate the genetic out- were described previously in multiple organisms (16, 17), Strep- in comes resulting from CRISPR-Cas targeting of integrated MGEs, tococcus thermophilus was the first microbe in which the roles silico prediction revealed four genomic islands without essential of specific cas genes and CRISPR-array components were elu- genes in lengths from 8 to 102 kbp, totaling 7% of the genome.
    [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]
  • Investigating Genetic (IN)Compatibility Between Temperate Phages and CRISPR-CAS Systems in Staphylococcus Aureus Gregory W
    Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2018 Investigating Genetic (IN)Compatibility Between Temperate Phages and CRISPR-CAS Systems in Staphylococcus Aureus Gregory W. Goldberg Follow this and additional works at: https://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons INVESTIGATING GENETIC (IN)COMPATIBILITY BETWEEN TEMPERATE PHAGES AND CRISPR-CAS SYSTEMS IN STAPHYLOCOCCUS AUREUS A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Gregory W. Goldberg June 2018 © Copyright by Gregory W. Goldberg 2018 INVESTIGATING GENETIC (IN)COMPATIBILITY BETWEEN TEMPERATE PHAGES AND CRISPR-CAS SYSTEMS IN STAPHYLOCOCCUS AUREUS Gregory W. Goldberg, Ph.D. The Rockefeller University 2018 Prokaryotic organisms employ various mechanisms for defending against parasitism by viruses and other mobile genetic elements. One form of defense comprises the adaptive immune systems derived from clustered, regularly interspaced, short palindromic repeat (CRISPR) loci and CRISPR-associated (cas) genes. CRISPR-Cas immune systems enable the acquisition of heritable resistance to specific mobile genetic elements on the basis of nucleic acid sequence recognition, but do not necessarily discriminate between target elements which are burdensome and those which are beneficial. My thesis is concerned with the consequences of CRISPR-Cas immunity directed at a particular breed of bacterial DNA viruses,
    [Show full text]
  • CRISPR-Cas3 of Salmonella Upregulates Bacterial Biofilm
    pathogens Article CRISPR-cas3 of Salmonella Upregulates Bacterial Biofilm Formation and Virulence to Host Cells by Targeting Quorum-Sensing Systems Luqing Cui 1,2, Xiangru Wang 1 , Deyu Huang 3, Yue Zhao 1, Jiawei Feng 1, Qirong Lu 3, Qinqin Pu 2, Yulian Wang 3, Guyue Cheng 3, Min Wu 2,* and Menghong Dai 1,* 1 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China; [email protected] (L.C.); [email protected] (X.W.); [email protected] (Y.Z.); [email protected] (J.F.) 2 Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA; [email protected] 3 MOA Key Laboratory of Food Safety Evaluation/National Reference Laboratory of Veterinary Drug Residue (HZAU), Huazhong Agricultural University, Wuhan 430070, China; [email protected] (D.H.); [email protected] (Q.L.); [email protected] (Y.W.); [email protected] (G.C.) * Correspondence: [email protected] (M.W.); [email protected] (M.D.); Tel.: +1-701-777-4875 (M.W.); +86-027-8767-2232 (M.D.); Fax: +1-701-777-2382 (M.W.); +86-027-8767-2232 (M.D.) Received: 8 December 2019; Accepted: 7 January 2020; Published: 10 January 2020 Abstract: Salmonella is recognized as one of the most common microbial pathogens worldwide. The bacterium contains the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems, providing adaptive immunity against invading foreign nucleic acids.
    [Show full text]