Accumulation of Succinyl Coenzyme A Perturbs the Methicillin-Resistant
            <i>Staphylococcus aureus</i>
            (MRSA) Succinylome and Is Associated with Increased Susceptibility to Beta-Lactam Antibiotics

Campbell, Christopher; Fingleton, Claire; Zeden, Merve S; Cendejas-Bueno, Emilio; Gallagher, Laura A.; Shinde, Dhananjay; Ahn, Jongsam; Olson, Heather; Fillmore, Thomas; Adkins, Joshua N.; Razvi, Fareha; Bayles, Kenneth W.; Fey, Paul D.; Thomas, Vinai Chittezham; Cava, Felipe; Clair, Gérémy; O’Gara, James P.

doi:10.1128/mbio.00530-21

Cited by 19 publications

(17 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A total of 3,260 succinylation sites in 799 proteins and 7,935 Kac sites from 1,710 proteins were detected in XN108-WT strain. The numbers of Ksucc and Kac sites reported in this study were greater than those identified previously ( 27 , 28 ), partially because of the benefit of the development and improvement of detection methodology. Another reason might be that different S. aureus strains with different backgrounds were used.…”

Section: Discussioncontrasting

confidence: 61%

“…Nevertheless, the work of PTM identification was seldom carried out in S. aureus . Only Zhang et al ( 27 ) and Campbell et al ( 28 ) detected the protein acetylation and succinylation in S. aureus before. In the present study, we conducted systematic analyses of both Ksucc and Kac modifications in S. aureus XN108, the first ST239 vancomycin-intermediate S. aureus (VISA) strain isolated in China ( 29 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Lysine Succinylome and Acetylome in the Vancomycin-Intermediate Staphylococcus aureus XN108

et al. 2022

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Identification of Lysine Succinylome and Acetylome in the Vancomycin-Intermediate Staphylococcus aureus XN108

et al. 2022

View full text Add to dashboard Cite

show abstract

“…9 A previous study has found that succinylation regulates autolysis and β-lactam susceptibility in methicillinresistant S. aureus, suggesting that the modulation of succinylation may affect antimicrobial susceptibility. 10 Our study also found succinylated protein and penicillinbinding protein 2, which may influence the antibiotic binding (Figure 1B). Thus, the drugs that modulate acetylation or succinylation will affect a wide range of functions in S. aureus, including antibiotic susceptibility.…”

Section: F I G U R E 2 Functional Classification and Gene Ontology (G...supporting

confidence: 65%

Proteomic profiling of lysine acetylation and succinylation in Staphylococcus aureus

Xia

Liu

et al. 2022

Clinical & Translational Med

View full text Add to dashboard Cite

Dear Editor,Although antimicrobial treatment of Staphylococcus aureus (S. aureus) infection is standard therapy for patients, mortality remains high as for the complications which include myocarditis. 1 Understanding the regulation of the proteome in the S. aureus bacterium may provide new insights in the treatment of this bacterial infection and also new basic knowledge of molecular signalling. Post-translational modification (PTM) of the lysine residue has significant consequences for functional and regulatory implications, including cytoskeleton complexes. 2 Specifically, N-lysine acetylation (Kac) and succinylation (Ksucc) prove to act as important PTMs for regulating various biological processes, including amino acid metabolism, protein translation and energy metabolism. 3,4 In this study, we systematically investigated lysine acetylation and succinylation sites in S. aureus using mass spectrometry (Supporting Information) and identified 1778 lysine acetylation sites from 794 proteins and 1651 lysine succinylation sites from 450 proteins. The finding, to our knowledge, is the largest number of acetylated and succinylated proteins to be discovered in S. aureus.Among the 794 lysine acetylated proteins in S. aureus, 48.1% and 6.3% have one or over five acetylated sites, respectively. We identified the top three proteins to be most poly-acetylated, which were oligopeptidase F (17 sites), phosphoglycerate kinase (11 sites) and elongation factor G (10 sites). For 450 lysine succinylated proteins, 33.3% were singly modified and 24.2% were poly-succinylated. The top three poly-succinylated proteins were bifunctional autolysin (23 sites), foldase protein PrsA (20 sites) and phosphoglycerate kinase (19 sites) (Figure 1A,B).To further characterize Kac and Ksucc sites, we examined the sequence motif around the identified peptides. Highly conserved motifs were found to be matched in the identified acetylated peptides (Figure 1C,F). These highly conserved motifs are consistent with previous reports, including eukaryotes, where Kac-tyrosine (Y) and Kachistidine (H) motifs were reported. 5,6 A heat map furtherThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

show abstract

“…For instance, almost 98% of the mutants of the V. cholerae transposon library present a statistically significant alteration of their PG profile (deviate at least 1SD from the average), and more than the 50% of the mutants presented a variation higher than 2SD of the average of the whole library for at least one muropeptide or a PG-feature) that included loci from all COG categories. These results are in agreement with studies that linked the cell wall with seemingly unrelated pathways/processes (e.g.,(Bancroft et al, 2020; Campbell et al, 2021; Masser et al, 2021)). Conversely, certain mutants in cell wall-annotated genes did not show an altered PG profile suggesting the existence of functional redundancies or condition-specific activities.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide peptidoglycan profiling of Vibrio cholerae

Hernández

Álvarez

Ritzl-Rinkenberger

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Most bacteria cells are protected by a peptidoglycan cell wall. Defining the chemical structure of the peptidoglycan has been instrumental to characterize cell wall associated proteins and to illuminate the mode of action of cell wall-acting antibiotics. However, a major roadblock for a comprehensive understanding of peptidoglycan homeostasis has been the lack of methods to conduct large-scale, systematic studies. Here we have developed and applied an innovative high throughput peptidoglycan analytical pipeline to analyze the entire non-essential, arrayed mutant library of Vibrio cholerae. The unprecedented breadth of these analyses revealed that peptidoglycan homeostasis is preserved by a large percentage of the genome organized in complex networks that functionally link peptidoglycan features with genetic determinants. As an example, we discovered a novel bifunctional penicillin-binding protein in V. cholerae. Collectively, genome-wide peptidoglycan profiling provides a fast, easy, and unbiased method for systematic identification of the genetic determinants of peptidoglycan synthesis and remodeling.

show abstract

Accumulation of Succinyl Coenzyme A Perturbs the Methicillin-Resistant Staphylococcus aureus (MRSA) Succinylome and Is Associated with Increased Susceptibility to Beta-Lactam Antibiotics

Cited by 19 publications

References 78 publications

Identification of Lysine Succinylome and Acetylome in the Vancomycin-Intermediate Staphylococcus aureus XN108

Identification of Lysine Succinylome and Acetylome in the Vancomycin-Intermediate Staphylococcus aureus XN108

Proteomic profiling of lysine acetylation and succinylation in Staphylococcus aureus

Genome-wide peptidoglycan profiling of Vibrio cholerae

Contact Info

Product

Resources

About