Environmental mycobacteria – Future directions

Abstract Understanding environmental mycobacteria and the diseases they cause is woefully lacking. The number of species, their ubiquity in nature and the heterogeneity of their effects on their human hosts have made this a formidable task. Diagnosis is difficult. Standard laboratory testing is controversial, and treatment lacks trial-based evidence. Uncertainty in epidemiology, pathogenesis, diagnosis, and treatment results in inconsistent clinical care for these diseases. The lack of tools to understand the organisms and diseases has stunted research in this field. Knowledge of nontuberculous mycobacteria pales compared to that of tuberculosis. Tuberculosis research and understanding have surged in recent years leading to better understanding, containment, and control of this disease. At the same time, diseases caused by nontuberculous mycobacteria have increased. The field of nontuberculous mycobacteria must learn from developing countries that have used technology to “leap-frog” over other technology that took decades to attain. “Omics” technology could be the key to raising the knowledge of nontuberculous mycobacteria to that of tuberculosis. Genome-based technology could replace the microbiology lab for diagnosis and drug sensitivity identification. It could vastly strengthen epidemiology, better define pathogenesis, effectively guide treatment, and accurately prognosticate outcomes. Genomics are already being used to track mycobacterial infections. Bacterial gene sequencing in patients with cystic fibrosis infected with Mycobacterium abscessus has shown the first human-to-human spread. Sequencing studies have separated out M. avium and M. intracellulare and have shown differences in pathogenicity. Studies on environmental isolation could yield clues to controlling these diseases by system modifications. Genomic approaches to pathogenesis have largely involved M. smegmatis, which has been used as a surrogate for M. tuberculosis in learning about the gene and protein changes that occur when bacteria go into a dormant state. Studies on M. ulcerans have identified factors related to its virulence. The mycobacterial diagnostic lab has used gene-based tests for several years, and there is a growing array of products available. Sequencing of the genes encoding the highly variable regions of bacterial DNA is rapid and accurate. Genotyping already can identify pathogenicity and response to antibiotics in a few instances; the future goal should be to identify sensitivity to a wide variety of organisms and antibiotics. This information will require clinical trials and time to validate it. An interferon gamma release assay for infection with nontuberculous mycobacteria is desperately needed. Success with tuberculosis was attained by finding bacterial antigens associated with virulence and invasive disease. This may be difficult because the damage caused by environmental mycobacteria tends to be epithelial and subepithelial. The cavities may be bronchiectatic in origin and deeper invasion may result from host reactions. Serologic testing has not yielded important clinical help for diseases caused by either M. tuberculosis or the nontuberculous mycobacteria, possibly because good bacterial or host response proteins have not been identified. This could change with a metabolomics approach. Genomic studies that give incremental gains may set the stage for major breakthroughs, but require coordination with good phenotyping. Tools are in place to open an exciting new era for understanding and control of mycobacteria.