High intracellular level of guanosine tetraphosphate in Mycobacterium smegmatis changes the morphology of the bacterium

Almost one-third of the world population today harbors the tubercle bacillu s asymptomatically. It is postulated that the morphology and staining patte rn of the long-term persistors are different front those of actively growin g culture. Interestingly, it has been found that the morphology and stainin g pattern of the starved in vitro population of mycobacteria is similar to the persistors obtained from the lung lesions. In order to delineate the bi ochemical characteristics of starved mycobacteria, Mycobacteria smegmatis w as grown in 9.2% glucose as a sole carbon source along with an enriched cul ture in 2% glucose. Accumulation of the stringent factor guanosine tetrapho sphate (ppGpp) with a concomitant change in morphology was observed for M. smegmatis under carbon-deprived conditions. In addition, M. smegmatis assum ed a coccoid morphology when ppGpp was ectopically produced by overexpressi ng Escherichia coli relA, even in an enriched medium. The Mycobacterium tub erculosis relA and spoT homologue, when induced in M. smegmatis, also resul ted in the overproduction of ppGpp with a change in the bacterium's growth characteristics.