Exceptionally versatile – arginine in bacterial post-translational protein modifications

Lassak, Jürgen; Koller, Franziska; Krafczyk, Ralph; Volkwein, Wolfram

doi:10.1515/hsz-2019-0182

Cited by 16 publications

(10 citation statements)

References 332 publications

(449 reference statements)

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“…Although the relatively inert guanidine group of arginine was previously thought to impede nucleophilic attack onto donor substrates, it is now clear that many bacterial enzymes have overcome this barrier. The enzymology and functional roles of arginine glycosylation, methylation, phosphorylation, and ADP-ribosylation were recently reviewed 14 .…”

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confidence: 99%

An intra-bacterial activity for a T3SS effector

Qaidi

Scott

Hays

et al. 2020

Sci Rep

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Many Gram-negative bacterial pathogens interact with mammalian cells by using type iii secretion systems (T3SS) to inject virulence proteins into host cells. A subset of these injected protein 'effectors' are enzymes that inhibit the function of host proteins by catalyzing the addition of unusual posttranslational modifications. The E. coli and Citrobacter rodentium NleB effectors, as well as the Salmonella enterica SseK effectors are glycosyltransferases that modify host protein substrates with N-acetyl glucosamine (GlcNAc) on arginine residues. This post-translational modification disrupts the normal functioning of host immune response proteins. T3SS effectors are thought to be inactive within the bacterium and fold into their active conformations after they are injected, due to the activity of chaperones that keep the effectors in a structural state permissive for secretion. While performing mass spectrometry experiments to identify glycosylation substrates of nleB orthologs, we unexpectedly observed that the bacterial glutathione synthetase (GshB) is glycosylated by NleB on arginine residue R256. NleB-mediated glycosylation of GshB resulted in enhanced GshB activity, leading to an increase in glutathione production, and promoted C. rodentium survival in oxidative stress conditions. these data represent, to our knowledge, the first intra-bacterial activity for a T3SS effector and show that arginine-GlcnAcylation, once thought to be restricted to host cell compartments, also plays an important role in regulating bacterial physiology.

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confidence: 99%

An intra-bacterial activity for a T3SS effector

Qaidi

Scott

Hays

et al. 2020

Sci Rep

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“…High expression levels of PDCL-3 increased the sensitivity to hypoxia stress and impacted on the interaction with vascular endogenous growth factor receptor 2 (VEGFR-2) leading to regulating angiogenesis in Zebrafish and mouse. In E. coli , acetylation of arginine site of ribosomal protein L12 not only affected the regulation of cell cycle, but also enhanced the stress resistance of bacteria by enhancing the intra-molecular interaction of ribosomal stalk 21 . Sclerotia formation is to adapt to the environment change.…”

Section: Discussionmentioning

confidence: 99%

Acetylome analysis of acetylation providing new insight into sclerotial generation in medicinal fungus Polyporus umbellatus

Liu

Shan

et al. 2022

Sci Rep

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Sclerotium-forming fungi are ecologically diverse and possess notable pathogenic or medicinal properties. The sclerotial generation mechanism is still elusive though Polyporus umbellatus sclerotia are typical Traditional Chinese Medicine with diuretic and antitumor effects. Protein acetylation displays a crucial role in several biological processes, but the functions of acetylation in this valuable fungus are unknown at present. In this study, acetylome of P. umbellatus was studied using nano LC-Triple TOF mass spectrometry system following immune-affinity-based enrichment. Totally, 648 acetylated sites in 342 proteins were identified and nine motifs were found to be conserved in P. umbellatus including KacY, KacA, KacL, KacG, MacS, MacA, RacA, RacL, and RacG. Acetylated proteins taken part in types of biological processes, particularly to those in biological processes associated with reactive oxygen species (ROS) metabolism. Inhibitors complement tests were carried out to verify the role of ROS in acetylation modification. It was concluded that oxidative stress regulated sclerotial generation via proteins acetylation in P. umbellatus. The present study presents new insight into the essential roles of acetylation in sclerotial formation, which may also be applicable for other sclerotium-forming fungi.

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“…It has been reported that K. pneumoniae in biofilms showed higher resistance to polymyxin than the planktonic cells ( Naparstek et al, 2014 ). This difference between protein level and phenotype may be caused by post-translational modifications of proteins ( Lassak et al, 2019 ). Defects in K. pneumoniae porins OmpK35 and OmpK36 (their E. coli homologs are OmpF and OmpC, respectively) could lead to reduced sensitivity to carbapenem ( Sugawara et al, 2016 ; Hamzaoui et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Cell Membrane Remodeling Mediates Polymyxin B Resistance in Klebsiella pneumoniae: An Integrated Proteomics and Metabolomics Study

et al. 2022

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Polymyxin B (PB) is introduced into the clinic as the last-line therapy against carbapenem-resistant Klebsiella pneumoniae (CRKP). Unfortunately, increased resistance to PB in Klebsiella pneumoniae (K. pneumoniae) has threatened global health. Resistance of K. pneumoniae to PB was induced by passaging in serial concentrations of PB and determined by microbroth dilution method. Growth characteristics of induced strains including growth curve, reversibility of resistance, and biofilm formation (crystal violet staining method) were measured. This study employed TMT-labeled quantitative proteomics and LC-MS/MS metabolomics analysis to investigate the key biological processes associated with PB resistance in K. pneumoniae. A total of 315 differentially expressed proteins (DEPs) were identified, of which 133 were upregulated and 182 were downregulated in the PB-resistant K. pneumoniae. KEGG enrichment analysis revealed that the DEPs were mainly involved in ATP-binding cassette (ABC) transporters and cationic antimicrobial peptide (CAMP) resistance. Proteins related to central carbon metabolism were inhibited in the PB-resistant K. pneumoniae, but proteins mediating LPS modification were activated. Transcriptional levels of CAMP resistance-related proteins were significantly different between PB-susceptible and -resistant K. pneumoniae. PB treatment led to an increase in reactive oxygen species (ROS) levels of K. pneumoniae. Metabolomics data demonstrated that 23 metabolites were significantly upregulated in PB-resistant K. pneumoniae and 5 were downregulated. The differential metabolites were mainly lipids, including glycerophospholipids, sphingolipids, and fatty acids. Exposure to PB resulted in increased level of phospholipid transport gene mlaF in K. pneumoniae. Our study suggested that membrane remodeling and inhibited central carbon metabolism are conducive to the development of PB resistance in K. pneumoniae.

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Exceptionally versatile – arginine in bacterial post-translational protein modifications

Cited by 16 publications

References 332 publications

An intra-bacterial activity for a T3SS effector

An intra-bacterial activity for a T3SS effector

Acetylome analysis of acetylation providing new insight into sclerotial generation in medicinal fungus Polyporus umbellatus

Cell Membrane Remodeling Mediates Polymyxin B Resistance in Klebsiella pneumoniae: An Integrated Proteomics and Metabolomics Study

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