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Mycobacterium avium subsp. hominissuis (MAH) is an opportunistic human pathogen that can cause lymphadenitis, pulmonary infections and disseminated infections. In addition, MAH is widespread in the environment, since it has been isolated from dust, soil and water. MAH isolates are characterized by high genetic diversity. Recently a new genomic island (GI), later re-named as hypervariable GI (hvGI), was identified in few MAH isolates, contributing to the genetic diversity of the MAH isolates.
It is not known whether clinical or environmental MAH isolates differ from each other. In this thesis we analyzed 41 MAH isolates from Germany isolated from clinical (n=20) and from environmental (n=21) source. First we identified and characterized the hvGI in all isolates, in order to see if the hvGI differentiates clinical and environmental MAH isolates. Then we investigated the function of the mmpL10 gene of the hvGI in order to get insights on the function of one of the genes present in the hvGI. We identified the hvGI in 39/41 isolates. We found high genetic diversity in the hvGI: eight types of hvGI have been identified (size 6.2-73.3 kb). Two types shared more than 80% sequence identity with Mycobacterium canettii responsible for Tuberculosis. We identified 253 different genes in all hvGIs, among which the previously documented virulence genes mmpL10 and mce. Functional studies on the mmpL10 gene suggest its involvement in antibiotic-resistance and in sugar transport. Our study expands the knowledge on MAH genome plasticity. The diversity of the hvGIs and the similarities with other mycobacteria suggests cross-species transfer. The shuffling of virulence/drug-resistance genes via the hvGIs may generate new variants able to can cause new outbreaks.
In addition, we analyzed ten MAH isolates at metabolic level using the BIOLOG Phenotype Microarray method, in order to see whether clinical or environmental MAH isolates show any metabolic differences. We found that MAH metabolized mostly fatty acids such as Tween, caproic, butyric and propionic acid. Clinical MAH metabolized stronger butyric (p = 0.0209) and propionic acid (p = 0.00307) compared environmental MAH. Our study provides new insight into the metabolism of MAH. Understanding how bacteria utilize substrates during infection might support the development of strategies to fight such infections.