Quantitative Proteomic and Phosphoproteomic Analysis of H37Ra and H37Rv Strains of <i>Mycobacterium tuberculosis</i>

Verma, Renu; Pinto, Sneha M.; Patil, Arun H.; Advani, Jayshree; Subba, Pratigya; Kumar, Manish; Sharma, Jyoti; Dey, Gourav; Ravikumar, Raju; Buggi, Shashidhar; Satishchandra, Parthasarathy; Sharma, Kusum; Suar, Mrutyunjay; Tripathy, Srikanth; Chauhan, D. S.; Gowda, Harsha; Pandey, Akhilesh; Gandotra, Sheetal; Prasad, T. S. Keshava

doi:10.1021/acs.jproteome.6b00983

Cited by 52 publications

(40 citation statements)

References 79 publications

(141 reference statements)

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“…Analysis of M. tuberculosis phosphoproteome suggests phosphorylation of over 300 proteins with more than 500 phosphopeptides detected under various host‐like stress conditions . Further phosphoproteomic studies in M. tuberculosis H37Rv or Beijing strain , revealed additional non‐redundant phosphorylated proteins belonging to multiple classes. The overlap between all three studies is limited to 56 proteins .…”

Section: Introductionmentioning

confidence: 99%

“…Tyrosine phosphorylation was the first Ser/Thr/Tyr phosphorylation to be detected in M. tuberculosis . According to phosphoproteome studies, the tyrosine phosphorylation account for only 3% to 4% of the total Ser/Thr/Tyr phosphorylations . There are two tyrosine phosphatases—PtpA and PtpB.…”

Section: Introductionmentioning

confidence: 99%

“…Further phosphoproteomic studies in M. tuberculosis H37Rv or Beijing strain , revealed additional non‐redundant phosphorylated proteins belonging to multiple classes. The overlap between all three studies is limited to 56 proteins . Taken together, the repertoire of serine/threonine phosphorylation's in M. tuberculosis now stands at over 700 proteins.…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2018

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“…Our meta-analyses show that at least 30% of the Mtb proteins undergo one or more type of PTM (Fig 2a). Acetylation [60] and phosphorylation [61–65] are the most common modifications in Mtb. Moreover, O-glycosylation [66,67], Pupylation (Prokaryotic Ubiquitin-Like Protein Modification) [68], lipidation [66], methylation, deamidation and N-formylation have been reported (Fig 2b, 2c) [69].…”

Section: Current Knowledge About the Proteome Of Mtbmentioning

confidence: 99%

Systems proteomics approaches to study bacterial pathogens: application to Mycobacterium tuberculosis

Banaei‐Esfahani

Nicod

Aebersold

et al. 2017

Current Opinion in Microbiology

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Significant developments and improvements in basic and clinical research notwithstanding, infectious diseases still claim at least 13 million lives annually. Classical research approaches have deciphered many molecular mechanisms underlying infection. Today it is increasingly recognized that multiple molecular mechanisms cooperate to constitute a complex system that is used by a given pathogen to interfere with the biochemical processes of the host. Therefore, systems-level approaches now complement the standard molecular biology techniques to investigate pathogens and their interactions with the human host. Here we review omic studies in Mycobacterium tuberculosis, the causative agent of tuberculosis, with a particular focus on proteomic methods and their application to the bacilli. Likewise, the discussed methods are directly portable to other bacterial pathogens.

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“…Among the tools to study the biology of MTB, M. tuberculosis H37Rv is a well-characterized human lung isolate and one of the most commonly used laboratory strains of M. tuberculosis . This virulent strain has been used in several investigations to understand the molecular mechanisms of MTB virulence, pathogenicity and persistence, as it provides a unique platform to investigate biochemical and signaling pathways associated with pathogenicity [6]. In particular, it has been extensively used to identify pathogen biomarkers of M. tuberculosis infection and disease.…”

Section: Introductionmentioning

confidence: 99%

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Tucci

Portela

Chetto³

et al. 2019

Preprint

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21 Despite being the subject of intensive research, tuberculosis, caused by Mycobacterium 22 tuberculosis, remains at present the leading cause of death from an infectious agent. Secreted 23 and cell wall proteins interact with the host and play important roles in pathogenicity. These 24 proteins have been explored as candidate diagnostic markers, potential drug targets or vaccine 25 antigens, and special attention has been given to the role of their post-translational 26 modifications. With the purpose of contributing to the proteomic characterization of this 27 important pathogen including an O-glycosylation profile analysis, we performed a shotgun 28 analysis of culture filtrate proteins of M. tuberculosis based on a liquid nano-HPLC tandem mass 29 spectrometry and a label-free spectral counting normalization approach for protein 30 quantification. We identified 1314 M. tuberculosis proteins in culture filtrate and found that the 31 most abundant proteins belong to the extracellular region or cell wall compartment, and that 32 the functional categories with higher protein abundance factor were virulence, detoxification 33 and adaptation, and cell wall and cell processes. In culture filtrate, 140 proteins were predicted 34 to contain one of the three types of bacterial N-terminal signal peptides. Besides, various 35 proteins belonging to the ESX secretion systems, and to the PE and PPE families, secreted by the 36 type VII secretion system using nonclassical secretion signals, were also identified. O-37 glycosylation was identified as a frequent modification, being present in 108 proteins, principally 38 lipoproteins and secreted immunogenic antigens. We could identify a group of proteins 39 consistently detected in previous studies, most of which were highly abundant proteins. 40 Interestingly, we also provide proteomic evidence for 62 novel O-glycosylated proteins, aiding 41 to the glycoproteomic characterization of relevant antigenic membrane and exported proteins. 48 HIV-positive people [1]. Although TB diagnosis and successful treatment averts millions of 49 deaths each year, there are still large and persistent gaps related to this infection that must be 50 resolved in order to accelerate progress towards the goal of ending the TB epidemic endorsed 51 by WHO [1]. 52 M. tuberculosis (MTB), has evolved successful mechanisms to circumvent the hostile 53 environment of the macrophage, such as inhibiting the phagosome-lysosome fusion and to 54 escape the acidic environment inside the phagolysosome [2]. MTB may be unique in its ability 55 to exploit adaptive immune responses, through inflammatory lung tissue damage, to promote 56 its transmission [3]. It has been proposed that this microorganism was pressed by an 57 evolutionary selection that resulted in an infection that induces partial immunity, where the 58 host survives a long period after being infected with the pathogen, aiding in microorganism 59 persistence and transmission [3]. MTB mechanisms of evasion of host immune system were 60 proposed to have c...

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Quantitative Proteomic and Phosphoproteomic Analysis of H37Ra and H37Rv Strains of Mycobacterium tuberculosis

Cited by 52 publications

References 79 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

Systems proteomics approaches to study bacterial pathogens: application to Mycobacterium tuberculosis

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

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