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AGGREGATIBACTER ACTINOMYCETEMCOMITANS EVOLVES IN VIVO
IN PATIENTS WITH PERIODONTAL DISEASE
by
Ruoxing Sun
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements of the Degree
MASTER OF SCIENCE
(CRANIOFACIAL BIOLOGY)
May 2012
Copyright 2012 Ruoxing Sun
Object Description
| Title | Aggregatibacter actinomycetemcomitans evolves in vivo in patients with periodontal disease |
| Author | Sun, Ruoxing |
| Author email | ruoxingsun@gmail.com;ruoxings@usc.edu |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Cranio-Facial Biology |
| School | School of Dentistry |
| Date defended/completed | 2012-05-04 |
| Date submitted | 2012-05-04 |
| Date approved | 2012-05-04 |
| Restricted until | 2012-05-04 |
| Date published | 2012-05-04 |
| Advisor (committee chair) | Chen, Casey |
| Advisor (committee member) |
Paine, Michael Zeichner-David, Maggie |
| Abstract | Background: Periodontal pathogen Aggregatibacter actinomycetemcomitans exhibits marked variations in genomic content among strains. Such variations presumably arise from different evolution pathways of A. actinomycetemcomitans strains. However, it is not known whether genomic variation of A. actinomycetemcomitans may occur during short-term persistent infections in vivo. Hypothesis: A. actinomycetemcomitans may evolve in vivo in patients with periodontal disease. If true, the genomic variation may be related to the adaption mechanisms of the bacteria to the host. The information may provide insight to the mechanisms of persistent infection of A. actinomycetemcomitans in humans. Methods: Four pairs of A. actinomycetemcomitans strains (SCC393/A160, SCC1398/SCC4092, SCC2302/AAS4a, S23A/I23C) (henceforth referred to as "paired strains") recovered from four individuals respectively over a period of 0~10 years were subjected to (i) whole genome sequencing (WGS), (ii) phylogenetic analysis, (iii) comparative genomic hybridization (CGH) with an A. actinomycetemcomitans pan-genome microarray, and (iv) PCR analysis to confirm the mutations in selected genes between the paired strains. Results: Each paired strains were confirmed to derive from a recent ancestral strain by phylogenetic analysis of 150 core genes. Indications for short-term evolution were obtained from two sets of the paired strains. Two genes (encoding hypothetical proteins) in strain SCC2302 (the first strain) were not detected in strain AAS4a (isolated three years later). For the pair of S23A/I23C (isolated at the same time), S23A had ten genes that were not detected in I23C. These ten genes were found to be part of a 24.1 Kb plasmid in S23A. An intact serotype-specific gene cluster was found in serotype b antigen expressing S23A. In contrast, nontypeable I23C was found to have a 353-bp reversion in the gene cluster, which apparently has inactivated two ORFs of the cluster. Conclusion: A. actinomycetemcomitans genomes are largely stable during short-term persistent infections in humans, but may evolve via gene gains/losses or mutations. |
| Keyword | Actinobacillus actinomycetemcomitans; aggressive periodontitis; comparative genomic hybridization; genomic stability; indel mutation; microarray analysis |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Sun, Ruoxing |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-SunRuoxing-766-0.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Full text | AGGREGATIBACTER ACTINOMYCETEMCOMITANS EVOLVES IN VIVO IN PATIENTS WITH PERIODONTAL DISEASE by Ruoxing Sun A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements of the Degree MASTER OF SCIENCE (CRANIOFACIAL BIOLOGY) May 2012 Copyright 2012 Ruoxing Sun |
