The Ser/Thr Protein Kinase Protein-Protein Interaction Map of M. tuberculosis*

Wu, Fanlin; Liu, Yin; Jiang, He‐wei; Luan, Yizhao; Zhang, Hainan; He, Xiang; Xu, Zhaowei; Hou, Jingli; Ji, Liyun; Xie, Zhi; Czajkowsky, Daniel M.; Yan, Wei; Deng, Jiao-Yu; Bi, Lijun; Zhang, Xian-En; Tao, Sheng-Ce

doi:10.1074/mcp.m116.065771

Cited by 32 publications

(35 citation statements)

References 58 publications

(70 reference statements)

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“…Protein phosphorylation has emerged as a powerful network, which controls the fundamental physiology as well as the pathogenicity of bacteria. Based on proteome microarray data, STPK‐protein interaction map was constructed, which showed 492 binding partners and 1,027 interactions . However, in order to gain a true insight of the multitude of cellular pathways that are regulated by a specific kinase, high throughput phosphoproteomic studies are the need of the hour.…”

Section: Discussionmentioning

confidence: 99%

Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development

2018

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The emergence of increasingly drug-resistant Mycobacterium tuberculosis strains has become a crucial public health concern. In order to effectively treat tuberculosis, it is imperative to find newer drug targets, which are important for the in vivo bacterial survival and persistence. Phosphorylation based signaling cascades modulated by eukaryotic-like serine/threonine protein kinases and phosphatase in M. tuberculosis, transduce extracellular stimuli to a cellular response ensuing pathogen's growth, persistence and pathogenesis. Of the 11 STPKs that M. tuberculosis genome encodes, three kinases, namely PknA, PknB and PknG and the sole serine/threonine phosphatase PstP are crucial for the intracellular survival of the bacteria. PknA and PknB regulates cell growth, cell wall synthesis and morphological changes during bacterial cell division; while PknG modulates metabolic changes in response to stress and aids in bacterial survival during latency like conditions. PstP functions to dephosphorylate STPKs and their substrates and hence is important at nearly all stages of infection. Here, we review the current knowledge on PstP, PknA, PknB and PknG based on the genetic, biochemical, and functional studies in M. tuberculosis physiopathology. We further explore the potential of these molecules as targets for therapeutic intervention and discuss the advancement made in the development of inhibitors against these targets. © 2018 IUBMB Life, 70(9):889-904, 2018.

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Section: Discussionmentioning

confidence: 99%

Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development

2018

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“…Genome-wide regulatory network for BQAPs was compiled from the given regulatory networks (Balázsi et al, 2008;Sanz et al, 2011;Minch et al, 2015). Genome-wide protein interaction network involving BQAPs was generated by merging the derived high-confidence protein interactions (Strong et al, 2003;Wang et al, 2010;Hegde et al, 2012;Liu et al, 2012;Szklarczyk et al, 2017;Wu et al, 2017). The gene expression correlations greater than 0.5 for BQAPs were obtained from Hegde et al (2012).…”

Section: Building Molecular Interaction Networkmentioning

confidence: 99%

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

Hegde

2020

Front. Microbiol.

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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.

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“…A recent study using a proteome microarray showed that PknG plays a role in regulating cell wall integrity via regulating biosynthesis of peptidoglycan, a key component of mycobacterial cell walls . PknG also reportedly promotes intrinsic resistance to antibiotics , stress response and biofilm formation .…”

Section: Protein Kinases Regulate Mycobacterial Adaptation and Survivmentioning

confidence: 99%

Tuberculosis: Smart manipulation of a lethal host

Chaurasiya

2018

Microbiology and Immunology

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Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a global threat to human health. Development of drug resistance and co-infection with HIV has increased the morbidity and mortality caused by TB. Macrophages serve as primary defense against microbial infections, including TB. Upon recognition and uptake of mycobacteria, macrophages initiate a series of events designed to lead to generation of effective immune responses and clearance of infection. However, pathogenic mycobacteria utilize multiple mechanisms for manipulating macrophage responses to protect itself from being killed and to survive within these cells that are designed to kill them. The outcomes of mycobacterial infection are determined by several host- and pathogen-related factors. Significant advancements in understanding mycobacterial pathogenesis have been made in recent years. In this review, some of the important factors/mechanisms regulating mycobacterial survival inside macrophages are discussed.

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The Ser/Thr Protein Kinase Protein-Protein Interaction Map of M. tuberculosis*

Cited by 32 publications

References 58 publications

Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development

Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development

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

Tuberculosis: Smart manipulation of a lethal host

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