Mycobacterium tuberculosis H37Rv has a single nucleotide polymorphism in PHoR which affects cell wall hydrophobicity and gene expression

Mycobacterium tuberculosis is a successful pathogen that can adapt to multiple environmental niches. As part of its repertoire of adaptive responses, two-component regulatory systems play a major role in co-ordinating gene expression at the global level. The PhoPR system controls major cellular functions, including respiration, lipid metabolism, the immediate and enduring hypoxic responses, stress responses and persistence. We identified a single nucleotide polymorphism (SNP) found in the sensor kinase (PhoR) of this system between two commonly used strains of M. tuberculosis, H37Rv (PhoRP152) and CDC1551 (PhoRL152). We constructed an isogenic strain of H37Rv carrying PhoRL152, as well as strains containing two different copies of the PhoPR locus, to determine the functional consequences of the SNP on phenotypic traits. The previously identified Apr locus was not acid-inducible in H37Rv, although it was in the CDC1551 strain. Surprisingly, the acid-responsive expression was not completely dependent on the PhoR SNP, and the locus remained constitutively expressed even in the isogenic strain H37Rv:PhoRL152. The pattern of expression in PhoPR merodiploid strains was more complex, with neither allele showing dominance. This suggests that Apr regulation is more complex than previously thought and that additional factors must be responsible for Apr upregulation in response to acid conditions. In contrast, differences we identified in cell hydrophobicity between the two strains were wholly dependent on PhoR, confirming its role as major regulator of cell wall composition. Thus the SNP in the sensor kinase has functional consequences which account for some of the differences between widely used laboratory strains.