The Mycobacterium tuberculosis sRNA F6 Modifies Expression of Essential Chaperonins, GroEL2 and GroES

• Published in: Microbiology spectrum 2021-10, Vol.9 (2), p.e0109521-e0109521
• Main Authors: Houghton, Joanna, Rodgers, Angela, Rose, Graham, D'Halluin, Alexandre, Kipkorir, Terry, Barker, Declan, Waddell, Simon J, Arnvig, Kristine B
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Bacterial - biosynthesis; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Bacteriology; Chaperonin 60 - biosynthesis; Disease Models, Animal; Gene Expression Regulation, Bacterial - genetics; Heat-Shock Proteins - biosynthesis; hypoxia; infection; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - metabolism; nutrient starvation; Research Article; RNA, Bacterial - genetics; RNA, Small Untranslated - genetics; Sigma Factor - genetics; small RNA; Starvation - pathology; Tuberculosis - pathology; Wayne model chaperonins
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/Spectrum.01095-21

Almost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of posttranscriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA F6 and shown it to be dependent on SigF for expression and significantly induced in starvation conditions and in a mouse model of infection. Further exploration of F6 using an starvation model of infection indicates that F6 affects the expression of the essential chaperonins GroEL2 and GroES. Our results point toward a role for F6 during periods of low metabolic activity typically associated with long-term survival of M. tuberculosis in human granulomas. Control of gene expression via small regulatory RNAs (sRNAs) is poorly understood in one of the most successful pathogens, Mycobacterium tuberculosis. Here, we present an in-depth characterization of the sRNA F6, including its expression in different infection models and the differential gene expression observed upon deletion of the sRNA. Our results demonstrate that deletion of F6 leads to dysregulation of the two essential chaperonins GroEL2 and GroES and, moreover, indicate a role for F6 in the long-term survival and persistence of M. tuberculosis in the human host.