Thesis (Ph. D.)--Illinois State University, 1977. / Title from title page screen, viewed Jan. 4, 2005. Dissertation Committee: A.G. Richardson (chair), H.E. Brockman, A.E. Liberta, D. McCracken, M.E. Neville. Includes bibliographical references (leaves 166-178) and abstract. Also available in print.

Thesis (Ph. D.)--Illinois State University, 1974. / Title from title page screen, viewed Nov. 1, 2004. Dissertation Committee: Herman Brockman, Arlan Richardson (co-chairs), Ione Rhymer, Fritz Schwalm, David Weber. Includes bibliographical references (leaves 116-128) and abstract. Also available in print.

Title from PDF of title page (University of Missouri--Columbia, viewed on February 23, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Dr. Jonathan A. Green. Vita Includes bibliographical references.

Thesis (Ph. D.)--Illinois State University, 1997. / Title from title page screen, viewed June 13, 2006. Dissertation Committee: Radheshyam K. Jayaswal (chair), Brian J. Wilkinson, Mathew J. Nadakavukaren, Herman E. Brockman, Alan J. Katz. Includes bibliographical references and abstract. Also available in print.

A gene duplication occurs in Salmonella typhimurium which involves about 30% of the genome. The frequency of formation and loss of this duplication was determined in a Rec.A⁻ strain and a PolA⁻ strain and compared to that of a RecA⁺, PolA⁺ strain. The frequency of formation was found to be reduced in both RecA⁻ and PolA⁻. strains. Loss of the duplication was eliminated in the RecA⁻ strain, while the frequency of loss was found to be greater in a PolA⁻ strain than in the PolA⁺ strain. The effect of UV irradiation on the formation of duplication was also compared for the three strains. There is an increase in the frequency of formation in both the PolA⁺, RecA⁺ and PolA⁻, RecA⁺ strains, the increase being greater in the PolA⁻ strain. The frequency of formation is reduced in the RecA⁻ strain. It is postulated that recA-dependent repair pathways are involved in the formation of the duplication, but there is at least one other pathway available. / Master of Science

A systematic study of a collection of Lon⁻ mutants has been made in order to determine whether their pleiotropic phenotype is due to mutations affecting one or more genes. A fine structure map of the lon locus was constructed by Pl mediated generalized transduction. The lon⁻ mutations were found to map in two "clusters" within the region. Phenotypic characterization of a set of isogenic Lon⁻ strains derived from these experiments indicated that all Lon-associated phenotypes (e.g. sensitivity to UV irradiation, decreased ability to inherit plasmid and prophage, abnormal polypeptide degradation and regulation of capsular polysaccharide biosynthesis) are differentially expressed in Lon⁻ strains. A direct correlation exists between the intracistronic ordering of the lon⁻ alleles and the degree of expression the Lon⁻ phenotypes in each strain. All isogenic Lon⁻ strains exhibit conditional lethality upon a nutritional shift-up. However, some filamenting Lon⁻ mutants are not able to overcome this defect when exposed to growth conditions known to promote cell division in Lon⁻ strains. Evidence was obtained that suggest a role for nucleotide pools in the control of cell division and capsular polysaccharide production. Reversion studies indicated that all lon⁻ mutations studied are point mutations. The failure to generate deletions of the lon region in χ573, an F' strain carrying the lac to minE region on the plasmid, and the inability to cure F' strains carrying a lon⁻ mutation on the plasmid suggest that the lon gene product may be indispensable for the cell's survival. From transductional crosses, two intermediate phenotypic classes: UV-resistant, mucoid (UV^RMuc), (Class A) and UV-sensitive, nonmucoid (UV^SRou) (Class B), were obtained that did not segregate colonies of the opposite morphology. Genetic analysis of these strains by back-transduction into a proC⁻ lon⁺ background, indicated that complete genetic separation of all Lon-associated phenotypes tested was not achieved, although differences in the expression of some of these persisted. Data obtained from complementation analysis ruled out the presence of two genes at the lon locus. The patterns of complementation observed were compatible with the existence of one lon gene, having at least two distinct domains, and whose product is a multifunctional polypeptide. / Ph. D.

Wong, Ah Ting. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (p. 125-130). / Abstracts in English and Chinese. / ABSTRACT --- p.V / 摘要 --- p.VIII / TABLE OF CONTENTS --- p.X / ACKNOWLEDGEMENTS --- p.XII / INTRODUCTION --- p.13 / Adaptive Mutation versus Spontaneous Mutation --- p.13 / Fluctuation Test --- p.13 / Adaptive Reversion of lacI - lacZ Fusion Mutant --- p.17 / Putative Models of Adaptive Mutation Mechanisms --- p.18 / Point Mutagenesis --- p.18 / Hypermutation --- p.19 / Gene Amplification --- p.21 / Controversy over the Mechanism of Adaptive Mutation --- p.21 / Induced Mutagenesis under Other Stresses --- p.23 / The General Stress Response --- p.23 / The SOS Response --- p.24 / Reduced Mismatch Repair --- p.24 / Adaptive Mutation in Other Micro-organisms --- p.25 / Mutation Generation under Antibiotic Stress --- p.26 / Fluoroquinolones --- p.26 / Beta-Lactams --- p.27 / Aminoglycosides --- p.27 / Justification and Objectives of this Study --- p.28 / MATERIAL AND METHODS --- p.30 / Bacterial Strains --- p.30 / Culture Media --- p.30 / Antibiotics --- p.30 / Resistance Induction Assay --- p.31 / Rationale of Experimental Design --- p.31 / Agar Selection Method --- p.32 / Broth Selection Method --- p.34 / Isolation of Organisms which Exhibited Reduced Drug Susceptibility and Determination the Minimal Inhibitory Concentration (MIC) --- p.36 / Indole Test --- p.37 / DNA Extraction --- p.37 / Polymerase Chain Reaction (PCR) on the gyrA and rpoB Genes --- p.37 / PCR Product Purification and Nucleotide Sequencing --- p.39 / RESULTS --- p.40 / Solid Agar Selection Approach --- p.41 / Broth Selection Approach --- p.48 / Strain MG1655 --- p.49 / Strain BW25113 --- p.53 / recA Deletion Mutant --- p.54 / mutS Deletion Mutant --- p.56 / DISCUSSION --- p.59 / Development of Resistance Induction Assay --- p.59 / Background Resistance to Gentamicin and Rifampicin --- p.62 / Resistance Induction Effect of Ciprofloxacin --- p.64 / Relative Effects of recA and mutS Deletion --- p.66 / Putative Origins of Antibiotic Resistance Gene Mutations --- p.69 / TABLES AND FIGURES --- p.71 / REFERENCES --- p.125

Thesis (Ph. D.)--Illinois State University, 1974. / Title from title page screen, viewed Oct. 28, 2004. Dissertation Committee: H.E. Brockman, A.G. Richardson (co-chairs), A.E. Liberta, H.W. Huizinga, D. McCracken, F. Schwalm. Includes bibliographical references (leaves 119-140) and abstract. Also available in print.

Thesis (Ph. D.)--Illinois State University, 1995. / Title from title page screen, viewed May 2, 2006. Dissertation Committee: Anthony J. Otsuka (chair), Herman E. Brockman, David W. Borst, H. Tak Cheung, Radheshyam K. Jayaswal. Includes bibliographical references (leaves 170-187) and abstract. Also available in print.

The emergence and spread of multi-drug resistant (MDR-TB) and extensively drugresistant tuberculosis (XDR-TB) are a major medical and public problem threatening the global health. The objectives of this study were to (i) determine the prevalence of MDR-TB and XDR-TB in the Eastern Cape; (ii) analyze patterns of gene mutations in MDR-TB and (iii) identify gene mutations associated with resistance to second line injectable drugs in XDR-TB isolates. A total of 1520 routine sputum specimens sequentially received within a period of 12 months i.e. February 2012 to February 2013 from all MDR-TB and XDR-TB patients treated by Hospitals and clinics in the Eastern Cape were included in this study, of which 1004 had interpretable results. Samples were analyzed with the Genotype MTBDRplus VER 2.0 assay kit (Hain Lifescience) for detection of resistance to Rifampicin and Isoniazid while solid and liquid culture drug susceptibility tests were used for ethambutol, streptomycin, ethionamide, ofloxacin, capreomycin and amikacin. PCR and sequence analysis of short regions of target genes gyrA, (encode subunit of DNA topoisomerase gyrase), rrs (16S rRNA) and tlyA (encodes a 2’-O-methyltransferase) were performed on 20 XDR-TB isolates. MTBDRplus kit results and drug susceptibility tests identified 462 MDR-TB, 284 pre-XDR and 258 XDR-TB isolates from 267 clinics and 25 hospitals in the Eastern Cape. There was a high frequency of resistance to streptomycin, ethionamide, amikacin, ofloxacin and capreomycin. Mutation patterns indicated differences between the health districts as well as differences between the facilities within the health districts. The most common mutation patterns observed were: (i) ΔWT3, ΔWT4, MUT1 [D516V+del515] (rpoB), ΔWT, MUT1 [S315T1] (katG), ΔWT1 [C15T] (inhA) [39 MDR, 204 XDR-TB and 214 pre XDR-TB isolates], (ii) ΔWT8, MUT3 [L533P+S531L] (rpoB), ΔWT, MUT1 [S315T1] [145 MDR, 18 pre-XDR and 3 XDR-TB solates] and (iii) ΔWT3, WT4 [D516Y+del515] (rpoB), ΔWT, MUT1 [S315T1] (katG) [75 MDR, 1 pre-XDR and 7 XDR-TB isolates]. Mutations in inhA promoter regions were strongly associated with XDR-TB isolates. Two thirds (66.6 percent (669/1004) of the isolates had inhA mutations present with 25.4 percent (170/669) found among the MDR isolates, 39.2 percent (262/669) among the pre-XDR isolates and 35.4 percent (237/669) among the XDR-TB isolates, which implies that these resistant isolates are being spread by transmission within the community and circulating in the province. There was good correlation between XDR-TB drug susceptibility test results and sequence analyses of the gyrA and rrs genes. The majority of XDR-TB isolates contained mutations at positions C269T (6/20) and 1401G (18/20) in gyrA and rrs genes respectively. Sequence analysis of short regions of gyrA and rrs genes may be useful for detection of fluoroquinolone and amikacin/ kanamycin resistance in XDR-TB isolates but the tlyA gene is not a sensitive genetic marker for capreomycin resistance. This study highlighted the urgent need for the development of rapid diagnostics for XDR-TB and raised serious concerns regarding ineffective patientmanagement resulting in ongoing transmission of extremely resistant strains of XDRTB in the Eastern Cape suggesting that the Eastern Cape could be fast becoming the epicenter for the development of Totally Drug-resistant Tuberculosis (TDR-TB) in South Africa.