Mycobacteria and their sweet proteins: An overview of protein glycosylation and lipoglycosylation in M. tuberculosis

Mehaffy, Carolina; Belisle, John T.; Dobos, Karen M.

doi:10.1016/j.tube.2019.01.001

Cited by 24 publications

(38 citation statements)

References 137 publications

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“…Apa (Rv1860), LppO (Rv2290), Rv2799 and Rv3491 [21]. Our results confirm the presence of glycosylated lipoproteins in culture filtrate aiding to the growing evidence for glycosylation of mycobacterial lipoproteins [18,21]. Besides, we identified mono- or polyhexose modifications in DsbF (Rv1677), a probable conserved lipoprotein.…”

Section: Resultssupporting

confidence: 81%

“…To complement our analysis, the presence of the most common naturally occurring glycan residues in mycobacteria was analyzed: hexoses, like mannose, glucose or galactose, which are highly reported in mycobacterial lipoproteins [18], deoxyhexoses, like fucose and rhamnose, that are important components of the cell surface glycans [51], the pentose sugar arabinose also reported in some glycoproteins [18] and as part of the mycolyl-arabinogalactan-peptidoglycan of the cell wall [52], and heptoses, recognized to be transferred by heptosyltransferases using ADP-heptose [53]. Our rationale was that the nano LC MS/MS technology used in this work, by having more than four orders of magnitude intrascan dynamic range and a femtogram-level sensitivity, would allow the direct identification of modified peptides, without previous affinity-based strategies for glycosylated protein enrichment.…”

Section: Resultsmentioning

confidence: 99%

“…Of the 108 identified glycoproteins 21 were identified as candidate glycoproteins in the lectin interacting enriched membrane protein using WGA-affinity capture [12]. Besides, 12 glycoproteins bearing mono- or polyhexose modifications in our analysis have been included in a recent review of protein glycosylation and lipoglycosylation in M. tuberculosis [18], where experimental evidence was summarized. Among them several lipoproteins are included: LprA (Rv1270c), LprF (Rv1368), LppO (Rv2290), LpqH (Rv3763), PstS1 (Rv0934) and Mpt83 (Rv2873).…”

Section: Resultsmentioning

confidence: 99%

“…This PTMs, mainly glycosylation, lipidation and phosphorylation, are involved in signaling and response to stress, adaptation to changing environments, regulation of toxic and damaged proteins, protein localization and host-pathogen interactions. In MTB, more frequently O-glycosylation events have been reported [17], being this post-translational modification often found, in conjunction with acylation, in membrane lipoproteins [18]. A mechanistic model of this modification was proposed in which the initial glycosyl molecule is transferred to the hydroxyl oxygen of the acceptor Thr or Ser residue, a process catalyzed by the protein O-mannosyltransferase (PMT) (Rv1002c) [19].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the vital importance of glycosylated proteins in MTB pathogenesis, the current knowledge in this regard is still limited. Recent evidence using whole cell extracts revealed that glycosylation could be much more frequent than previously thought, explaining the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex [17], but in culture filtrates of this pathogen only a few secreted and cell wall-associated glycoproteins have been described to date [18,21].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Tucci

Portela

Chetto³

et al. 2019

Preprint

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show abstract

Effects of Mycobacterium tuberculosis Rv1096 on mycobacterial cell division and modulation on macrophages

Deng

Shi

et al. 2020

Microbial Pathogenesis

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Higher Temperature Porous Graphitic Carbon Separations Differentially Impact Distinct Glycopeptide Classes

Delafield

Miles

Ricke

et al. 2022

J. Am. Soc. Mass Spectrom.

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Mass spectrometry-based discovery glycoproteomics is highly dependent on the use of chromatography paradigms amenable to analyte retention and separation. When compared against established stationary phases such as reversed-phase and hydrophilic interaction liquid chromatography, reports utilizing porous graphitic carbon have detailed its numerous advantages. Recent efforts have highlighted the utility in porous graphitic carbon in high-throughput glycoproteomics, principally through enhanced profiling depth and liquid-phase resolution at higher column temperatures. However, increasing column temperature has been shown to impart disparaging effects in glycopeptide identification. Herein we further elucidate this trend, describing qualitative and semiquantitative effects of increased column temperature on glycopeptide identification rates, signal intensity, resolution, and spectral count linear response. Through analysis of enriched bovine and human glycopeptides, species with high mannose and sialylated glycans were shown to most significantly benefit and suffer from high column temperatures, respectively. These results provide insight as to how porous graphitic carbon separations may be appropriately leveraged for glycopeptide identification while raising concerns over quantitative and semiquantitative label-free comparisons as the temperature changes. RAW MS glycoproteomic data are available via ProteomeXchange with identifier PXD034354.

show abstract

Mycobacteria and their sweet proteins: An overview of protein glycosylation and lipoglycosylation in M. tuberculosis

Cited by 24 publications

References 137 publications

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Effects of Mycobacterium tuberculosis Rv1096 on mycobacterial cell division and modulation on macrophages

Higher Temperature Porous Graphitic Carbon Separations Differentially Impact Distinct Glycopeptide Classes

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