Published on September 2019 | Mycobacterium bovis, Mycobacterium tuberculosis, Biofilm, Sigma Factor, Lipid analysis, Proteomics, Pathogenesis, Surface phenotype, Antibiotic Susceptibility, Mutant, Knockout,

Mycobacterium bovis sigF mutant exhibits altered surface phenotype and compromised pathogenesis

Mycobacterium bovis belongs to the Mycobacterium tuberculosis complex (MTBC) which displays the broadest spectrum of host infection affecting humans, bovines and goats [1]. They succeeded as a pathogen due to its ability to adapt to a range of stresses imposed by the host immune system. They sense the host cellular environment and regulate their gene expression in response to prevailing conditions. Gene expression in bacteria is regulated primarily at the level of transcription initiation. Sigma factors guide the RNA polymerase enzyme complex to specific promoter sequences to initiate transcription of genes. M. bovis genome encodes 13 sigma factors [2]. The sigma factor F, SigF, was deemed as a stationary phase stress response sigma factor present only in slow-growing mycobacterial species [3]. However, later it was found to be widely conserved among mycobacteria [4, 5]. In mice, the M. tuberculosis ΔsigF mutant showed attenuated disease pathology [6, 7]. In non-tuberculous, rapid-growing mycobacteria, sigF is constitutively expressed throughout the growth, suggesting its wider role in mycobacteria in addition to virulence gene regulation in M. tuberculosis [5, 8]. In M. tuberculosis SigF regulon largely comprises genes with predicted roles in stress response and virulence [9, 10]. In M. smegmatis SigF regulon identified genes reportedly involved in oxidative stress and stationary phase adaptation [11, 12]. In this study, we report a detailed analysis of the surface phenotype of the ΔsigF mutant in M. bovis, its proteome profile and in vivo pathogenicity in a mouse model.