Molecular characterisation and immunological analysis of clinical and environmental isolates of Mycobacterium kansasii from South African gold mines
Year: 2011
Type: dissertation
Abstract: The South African gold-mining workforce has an unusually high incidence of Mycobacterium kansasii disease, yet little is known about the possible sources of M. kansasii \ninfection, genetic diversity and the basis for this organism’s pathogenicity. The purpose of \nthis study was to investigate these issues in a gold-mining environment. Five M. kansasii \nisolates and 10 other potentially pathogenic mycobacteria were cultured mainly from \nshowerhead biofilms. PCR-restriction analysis (PRA) of the hsp65 gene on 191 clinical and \non the 5 environmental M. kansasii isolates revealed 160 subtype I (157 clinical and 3 \nenvironmental), 8 subtype II (clinical) and 6 subtype IV (5 clinical and 1 environmental) \nstrains. Twenty-two isolates (21 clinical and 1 environmental) did not show the typical M. \nkansasii PRA patterns. After confirmation by DNA sequencing as belonging to the M. \nkansasii species, the results suggested that these isolates were probably new subtypes of M. \nkansasii. In contrast to the clonal population structure found amongst the subtype I isolates \nfrom studies in other countries, DNA fingerprinting of 114 subtype I clinical and \nenvironmental isolates showed genetic diversity amongst the isolates. One of the \n2 \nenvironmental isolates showed 100% identity with a clinical isolate, suggesting that water \ndistribution systems are the possible sources of M. kansasii infection for the miners. An \ninvestigation into the genetic differences between clinical (subtype I) and environmental (III, \nIV and V) isolates, using Hybridisation Monitored Differential Analysis (HMDA), identified \n45 open reading frames (ORFs) encoding predominantly membrane-associated proteins that \ninclude six potential virulence factors, two family members of transcription regulators for \ndrug and xenobiotic metabolism, three family members of multidrug efflux systems, a \nnumber of proteins associated with lipid and carbohydrate metabolism and transport, and a \nnumber of hypothetical proteins with unknown function. Immunological analysis of M. \nkansasii isolates, using the Lymphocyte Transformation and Cytometric Bead Array assays, \nshowed that M. kansasii modulates immune responses through suppression of lymphocyte \nblastogenesis and by altering the expression of Th1/Th2/Th17 cytokines by human \nlymphocytes in vivo for its own survival. This study demonstrated for the first time that water \ndistribution systems in South Africa are possible sources of M. kansasii infection, and \nshowed that subtype I strains of M. kansasii from the study region display genetic diversity \nand have unique or divergent genes not found in other subtypes. It also demonstrated that \nimmunosuppression is one of the pathogenic mechanisms employed by M. kansasii.
Author: Geoffrey Kwenda
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2247548526