GENETIC ANALYSIS OF CLOSTRIDIUM PERFRINGENS: INSIGHT INTO EVOLUTION OF VIRULENCE

Persistent Link:
http://hdl.handle.net/10150/194650
Title:
GENETIC ANALYSIS OF CLOSTRIDIUM PERFRINGENS: INSIGHT INTO EVOLUTION OF VIRULENCE
Author:
Sawires, Youhanna Sobhy
Issue Date:
2005
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Clostridium perfringens is an important pathogen in veterinary and medical fields. Understanding epidemiology of C. perfringens diseases and evolution of virulence within C. perfringens necessitates an efficient, time and cost effective strain typing method. Multiple-locus variable-number tandem repeat analysis (MLVA) has been applied to typing of other pathogens and we describe here the development of a MLVA scheme for C. perfringens. We characterized five VNTR loci, and screened 112 C. perfringens isolates to evaluate typability, reproducibility, and discriminatory power of the scheme. All isolates were assigned a MLVA genotype and the technique has excellent reproducibility, with a numerical index of discrimination of 0.995. Thus, MLVA is an efficient tool for C. perfringens strain typing, and being PCR based makes it rapid, easy, and cost effective. In addition, it can be employed in epidemiological, ecological, and evolutionary investigations of the organism.Virulence of this species is not fully understood and it does seem that distribution of the toxin/enzyme genes is erratic within the population. We used the MLVA scheme to investigate evolution of virulence and population structure of this species. Analysis of the phylogenetic signal indicates that acquisition of the major toxin genes and other plasmid-borne toxin genes is a recent evolutionary event, and their maintenance is essentially a function of the selective advantage they confer to strains carrying them in certain micro-niches under different conditions. In addition, it indicates the ability of virulent strains to cause disease in different hosts. More interestingly, there is evidence that certain normal flora strains are virulent when they gain access to a different host species. Analysis of the population structure indicates that recombination events are the major tool that shapes the population and this panmixia is interrupted with frequent clonal expansion that mostly corresponds to disease processes. Signature of positive selection was detected in the alpha toxin gene, suggesting the possibility of adaptive alleles on the other chromosomally-encoded determinants. Finally, C. perfringens proved to have a dynamic population, and availability of more genome sequences, use of comparative proteomics and of animal models would provide more insight into the pathogenicity of this organism.
Type:
text; Electronic Dissertation
Keywords:
Clostridium perfringens; MLVA; Virulence; Evolution; Strain typing; Epidemiology
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Pathobiology; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Songer, J. Glenn

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleGENETIC ANALYSIS OF CLOSTRIDIUM PERFRINGENS: INSIGHT INTO EVOLUTION OF VIRULENCEen_US
dc.creatorSawires, Youhanna Sobhyen_US
dc.contributor.authorSawires, Youhanna Sobhyen_US
dc.date.issued2005en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractClostridium perfringens is an important pathogen in veterinary and medical fields. Understanding epidemiology of C. perfringens diseases and evolution of virulence within C. perfringens necessitates an efficient, time and cost effective strain typing method. Multiple-locus variable-number tandem repeat analysis (MLVA) has been applied to typing of other pathogens and we describe here the development of a MLVA scheme for C. perfringens. We characterized five VNTR loci, and screened 112 C. perfringens isolates to evaluate typability, reproducibility, and discriminatory power of the scheme. All isolates were assigned a MLVA genotype and the technique has excellent reproducibility, with a numerical index of discrimination of 0.995. Thus, MLVA is an efficient tool for C. perfringens strain typing, and being PCR based makes it rapid, easy, and cost effective. In addition, it can be employed in epidemiological, ecological, and evolutionary investigations of the organism.Virulence of this species is not fully understood and it does seem that distribution of the toxin/enzyme genes is erratic within the population. We used the MLVA scheme to investigate evolution of virulence and population structure of this species. Analysis of the phylogenetic signal indicates that acquisition of the major toxin genes and other plasmid-borne toxin genes is a recent evolutionary event, and their maintenance is essentially a function of the selective advantage they confer to strains carrying them in certain micro-niches under different conditions. In addition, it indicates the ability of virulent strains to cause disease in different hosts. More interestingly, there is evidence that certain normal flora strains are virulent when they gain access to a different host species. Analysis of the population structure indicates that recombination events are the major tool that shapes the population and this panmixia is interrupted with frequent clonal expansion that mostly corresponds to disease processes. Signature of positive selection was detected in the alpha toxin gene, suggesting the possibility of adaptive alleles on the other chromosomally-encoded determinants. Finally, C. perfringens proved to have a dynamic population, and availability of more genome sequences, use of comparative proteomics and of animal models would provide more insight into the pathogenicity of this organism.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectClostridium perfringensen_US
dc.subjectMLVAen_US
dc.subjectVirulenceen_US
dc.subjectEvolutionen_US
dc.subjectStrain typingen_US
dc.subjectEpidemiologyen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePathobiologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairSonger, J. Glennen_US
dc.contributor.committeememberJoens, Lynn A.en_US
dc.contributor.committeememberDial, Sharonen_US
dc.identifier.proquest1231en_US
dc.identifier.oclc137354503en_US
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