Computational Identification of the Proteins Associated With Quorum Sensing and Biofilm Formation in Mycobacterium tuberculosis

Abstract

With prolonged therapy and increased instances of drug resistance, tuberculosis is viewed as a serious infectious disease causing high mortality. Emerging concepts in Mycobacterium tuberculosis pathogenicity include biofilm formation, which endows bacterial survival in the host for a long time. To tackle chronic tuberculosis infection, a detailed understanding of the bacterial survival mechanisms is crucial. Using comparative genomics and literature mining, 115 M. tuberculosis proteins were shortlisted for their likely association with biofilm formation or quorum sensing. These include essential genes such as secA2, lpqY-sugABC, Rv1176c, and Rv0195, many of which are also known virulence factors. Furthermore, the functional relationship among these proteins was established by considering known protein-protein interactions, regulatory interactions, and gene expression correlation data/information. Graph centrality and motif analyses predicted the importance of proteins, such as Rv0081, DevR, RegX3, Rv0097, and Rv1996 in M. tuberculosis biofilm formation. Analysis of conservation across other biofilm-forming bacteria suggests that most of these genes are conserved in mycobacteria. As the processes, such as quorum sensing, leading to biofilm formation involve diverse pathways and interactions between proteins, these system-wide studies provide a novel perspective toward understanding mycobacterial persistence.

Host‐directed therapy to combat mycobacterial infections*

“…By contrast, FDA‐approved HDACi suberoylanilide hydroxamic acid (SAHA) had no direct effect on Mtb growth, but it reduced mycobacterial growth via host‐directed mechanisms and synergized with rifampicin/isoniazid therapy 117 . As Rv1151c is well conserved across different mycobacterial species including Mav, 118 the above therapies may also be efficacious against NTM.…”

Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity

“…Furthermore, environmental conditions, such as nutrients, ions, and carbon sources, potentially influence mycobacterial behavior and have a regulatory role in biofilm formation [ 38 , 43 , 44 ]. Moreover, similar to other bacteria, this process may depend on a number of proteins associated with quorum sensing that ensure intercellular communication [ 44 , 45 , 46 ]. The ability of bacteria to form biofilms is undoubtedly one of the important pathogenicity factors that makes bacterial pathogens more persistent, more resistant to most antibiotics, and more resilient to host immunity, increasing the difficulty of their eradication [ 36 ].…”

Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis

“…The genetic determinants of M. tb biofilm formation have been investigated with candidate gene approaches and phenotypic characterization of knockout, knockdown, and overexpression mutants ( Ojha et al, 2008 ; Pang et al, 2012 ; Sambandan et al, 2013 ; Wolff et al, 2015 ; Rastogi et al, 2017 ; Yang et al, 2017 ; Richards et al, 2019 ; Hegde, 2019 ; Bharti et al, 2021 ; Chakraborty et al, 2021 ). Here, we use a complementary approach based on serial passaging of M. tb clinical isolates under selective pressure to grow as a biofilm.…”