The Influence of Glycerol and Specific Genes on the Asymmetric Cell Division in Mycobacteria

Abstract

The Influence of Glycerol and Specific Genes on the Asymmetric Cell Division in Mycobacteria Submitted by Atul Pradhan (S.R. No. 03-04-00-10-11-14-1-11678) Background Information: Mycobacteria maintain heterogeneity in cell-length, morphology, and metabolic differences in in vitro cultures, infected mice and guinea pigs, and tuberculosis patients. We had reported that ~20-30% of the septating mid-log phase cells of Mycobacterium smegmatis, Mycobacterium tuberculosis, and Mycobacterium xenopi undergo highly deviated asymmetric constriction during division (ACD) to generate short-sized cells (SCs) and normal/long-sized cells (NCs) as sister-daughter cells having differential susceptibility to oxidative/nitrite/antibiotic stress. The remaining 70-80% of the septating cells undergo more-or-less symmetric constriction during division (SCD) generating sister-daughter cells of more-or-less comparable length, as shown by us and other groups. We found that cell-length heterogeneity was achieved in mycobacteria by generating differently sized sister-daughter cells through ACD of NCs and SCD of SCs and NCs, as one of the mechanisms. Subsequently, we discovered Ap6A as the molecule, which gets secreted into the growth medium, that induces ACD in M. smegmatis and M. tuberculosis in a paracrine/autocrine manner and the levels of which in change with growth phase. Ap4A, which was introduced into the medium, was also found to induce ACD. In Escherichia coli and Bacillus subtilis, cell-size heterogeneity is affected by the availability of glucose in the culture medium for which UDP-glucose (UDPG) serves as the intracellular proxy for nutrient availability and its concentration decides the cell size during the division. In the present study on M. smegmatis, despite the absence of the orthologues of UgtP of B. subtilis and OpgH of E. coli that are involved in UDPG metabolism, we examined the influence of glycerol on the proportions of cells undergoing division by ACD and SCD...