THE ROLE OF HFLX, A HIGHLY CONSERVED GTPASE, IN MYCOBACTERIUM TUBERCULOSIS

Abstract

HflX is a universally conserved prokaryotic GTPase (ucpGTPase) which functions as a probable ribosomal-splitting factor in mycobacteria. Consistently, the absence of HflX was found to have a substantial amount of impact on BCG survivability under in vitro hypoxic conditions but not in a nutrient-starved environment. However, hflX deletion failed to impair BCG viability during infection of primary macrophages, and in the mouse lung and spleen. Instead, the ΔhflX BCG strain displayed a growth advantage compared to its parental counterpart in both models, suggesting HflX being a negative regulator of mycobacterial growth rate. HflX structure was observed to be significantly conserved in our computational analyses and we subsequently confirmed its role in preserving mycobacterial viability in BCG when exposed to elevated temperatures. In conclusion, HflX characterisation is the first step in understanding the role of conserved GTPases in pathogenic mycobacteria, especially in mycobacterial growth and survival.