Temperature and pH growth preferences predict the pathogenicity and environmental distributions of nontuberculous...

The genus Mycobacterium is highly diverse, and in addition to Mycobacterium tuberculosis, it includes many other pathogenic and non-pathogenic taxa which are collectively referred to as the nontuberculous mycobacteria. Although a subset of nontuberculous mycobacteria are of known clinical significance, the specific traits that dictate pathogenicity remain largely undetermined. We hypothesized that pathogenic nontuberculous mycobacteria are likely to have optimal growth at low pH (~pH 4.5-5.5) and at temperatures near that of the human body (~37°C), enabling survival within human tissues. To test this hypothesis, we measured the growth preferences of 20 strains of nontuberculous mycobacteria, spanning the breadth of diversity across the genus, using cellular activity as a proxy for growth in vitro. Pathogens tended to share preferences for optimal growth at lower pH and higher temperature conditions, while those of limited or no clinical significance generally had growth optima outside a range that would be conducive to effective growth within the human body. We then used our in vitro measurements of pH preferences to determine if we could predict the environmental distributions of nontuberculous mycobacteria, as determined from a cultivation-independent survey of 143 soils across the United States. We show that the measured in vitro pH preferences effectively predicted the distributions of nontuberculous mycobacteria in soil. Our work highlights the broad range in pH and temperature preferences across the genus, demonstrates the utility of these measurements for differentiating human pathogens from non-pathogens, and describes how measured growth preferences can be used to predict the environmental distributions of nontuberculous mycobacteria.IMPORTANCEThe genus Mycobacterium includes Mycobacterium tuberculosis as well as over 200 taxa collectively referred to as the nontuberculous mycobacteria (NTM). Although most nontuberculous mycobacteria have limited clinical significance, a handful of species within the genus are responsible for a growing number of chronic infections worldwide-yet the traits that underlie their pathogenicity remain largely undetermined. We measured the growth preferences of 20 strains of nontuberculous mycobacteria in vitro, finding that NTM pathogens tended to share preferences for optimal growth at lower pH and higher temperature (similar to conditions encountered in a human host), while those of no clinical significance generally had growth optima outside the conditions of the human body. We then used our in vitro measurements to show that we could predict the distributions of nontuberculous mycobacteria in soil, an important environmental reservoir and potential source of exposure and subsequent infection. Our work highlights not only the broad range in pH and temperature preferences across the genus, but the utility of measuring these traits for understanding NTM pathogenicity and ultimately, advancing our understanding of the ecology of nontuberculous mycobacteria.