PURPOSE: Mycobacterium massiliense is a new subspecies of M.abscessus that causes skin/soft tissue infection or chronic pulmonary disease in humans. However little is yet known about its disease pathogenesis in humans. Our objective was to determine whether there were any differences in virulence between the isolates acquired during the severe respiratory decline preceding death compared to those from a relatively asymptomatic period in a cystic fibrosis patient who died with nontuberculosis mycobacterial pulmonary disease.
METHODS: We assessed relatedness among the multiple serial isolates from the patient by typing with repetitive-sequence based PCR as well as multilocus sequence analysis of 16SRNA, hsp65, secA and rpoB genes. We also measured cytokine levels and mRNA expression after stimulating peripheral blood mononuclear cells and alveolar macrophages from normal subjects with each isolate.
RESULTS: All serial isolates appeared to be clonally related. Interestingly, we found that the isolate obtained just prior to the patient's death induced more TNF-α and mRNA expression of TNF-α compared to the other isolates. Moreover, this strain also exhibited increased bacterial uptake than the others in a macrophage infection assay. Induction of TNF-α was not dependent on nuclear factor-κB pathway.
CONCLUSION: These findings demonstrated the isolates from the same patient could change and acquire more virulence inside host cells and which may contribute to a decompensation of mycobacterial lung disease.
CLINICAL IMPLICATIONS: Acquirement of new virulence of the same clonal mycobacterium should be considered in acute clinical deterioration of nontuberculosis mycobacterial disease.
DISCLOSURE: Kenneth Olivier, No Financial Disclosure Information; No Product/Research Disclosure Information