RESUMO
Mycobacterium tuberculosis (MTb) is the causative agent of pulmonary tuberculosis (TB). MTb colonizes the human lung, often entering a non-replicating state before progressing to life-threatening active infections. Transcriptional reprogramming is essential for TB pathogenesis. In vitro, Cmr (a member of the CRP/FNR super-family of transcription regulators) bound at a single DNA site to act as a dual regulator of cmr transcription and an activator of the divergent rv1676 gene. Transcriptional profiling and DNA-binding assays suggested that Cmr directly represses dosR expression. The DosR regulon is thought to be involved in establishing latent tuberculosis infections in response to hypoxia and nitric oxide. Accordingly, DNA-binding by Cmr was severely impaired by nitrosation. A cmr mutant was better able to survive a nitrosative stress challenge but was attenuated in a mouse aerosol infection model. The complemented mutant exhibited a â¼2-fold increase in cmr expression, which led to increased sensitivity to nitrosative stress. This, and the inability to restore wild-type behaviour in the infection model, suggests that precise regulation of the cmr locus, which is associated with Region of Difference 150 in hypervirulent Beijing strains of Mtb, is important for TB pathogenesis.
Assuntos
Proteínas de Bactérias/genética , Mycobacterium tuberculosis/metabolismo , Proteínas Quinases/genética , Fatores de Transcrição/fisiologia , Tuberculose/microbiologia , Animais , Proteínas de Bactérias/metabolismo , Células Cultivadas , Proteínas de Ligação a DNA , Escherichia coli , Feminino , Regulação Bacteriana da Expressão Gênica , Macrófagos/microbiologia , Camundongos Endogâmicos BALB C , Mycobacterium smegmatis , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Oxirredução , Ligação Proteica , Proteínas Quinases/metabolismo , Transcrição Gênica , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismoRESUMO
Mycobacterium africanum is endemic to West Africa and is rare outside this region. Most of the people infected with M. africanum outside Africa are migrants from affected parts of Africa. We report a rare case of pulmonary tuberculosis (TB) secondary to M. africanum in a man in Brunei Darussalam who had lived and worked in Guinea, West Africa for 6 years more than 20 years ago. He had been well until December 2020, when he presented with a chronic cough and was diagnosed with coinfections of Klebsiella pneumoniae and M. africanum, and newly diagnosed diabetes mellitus. This case highlights an interesting manifestation of pulmonary TB secondary to M. africanum in a patient whose last exposure was 20 years ago, contributed to by development of diabetes mellitus.