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Accumulation of suc...
Accumulation of succinyl coenzyme a perturbs the methicillin-resistant staphylococcus aureus (Mrsa) succinylome and is associated with increased susceptibility to beta-lactam antibiotics
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- Campbell, Christopher (författare)
- Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland
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- Fingleton, Claire (författare)
- Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland
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- Zeden, Merve S. (författare)
- Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland
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- Bueno, Emilio (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Gallagher, Laura A. (författare)
- Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland
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- Shinde, Dhananjay (författare)
- Department of Pathology and Microbiology, University of Nebraska Medical Center, NE, Omaha, United States
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- Ahn, Jongsam (författare)
- Department of Pathology and Microbiology, University of Nebraska Medical Center, NE, Omaha, United States
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- Olson, Heather M. (författare)
- Biological Sciences Division, Pacific Northwest National Laboratory, WA, Richland, United States
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- Fillmore, Thomas L. (författare)
- Biological Sciences Division, Pacific Northwest National Laboratory, WA, Richland, United States
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- Adkins, Joshua N. (författare)
- Biological Sciences Division, Pacific Northwest National Laboratory, WA, Richland, United States
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- Razvi, Fareha (författare)
- Department of Pathology and Microbiology, University of Nebraska Medical Center, NE, Omaha, United States
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- Bayles, Kenneth W. (författare)
- Department of Pathology and Microbiology, University of Nebraska Medical Center, NE, Omaha, United States
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- Fey, Paul D. (författare)
- Department of Pathology and Microbiology, University of Nebraska Medical Center, NE, Omaha, United States
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- Thomas, Vinai C. (författare)
- Department of Pathology and Microbiology, University of Nebraska Medical Center, NE, Omaha, United States
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- Cava, Felipe (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Clair, Geremy C. (författare)
- Biological Sciences Division, Pacific Northwest National Laboratory, WA, Richland, United States
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- O’gara, James P. (författare)
- Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland
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(creator_code:org_t)
- American Society for Microbiology, 2021
- 2021
- Engelska.
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 12:3
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Penicillin binding protein 2a (PBP2a)-dependent resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) is regulated by the activity of the tricarboxylic acid (TCA) cycle via a poorly understood mechanism. We report that mutations in sucC and sucD, but not other TCA cycle enzymes, negatively impact β-lactam resistance without changing PBP2a expression. Increased intracellular levels of succinyl coenzyme A (succinyl-CoA) in the sucC mutant significantly perturbed lysine succinylation in the MRSA proteome. Suppressor mutations in sucA or sucB, responsible for succinyl-CoA biosynthesis, reversed sucC mutant phenotypes. The major autolysin (Atl) was the most succinylated protein in the proteome, and increased Atl succinylation in the sucC mutant was associated with loss of autolytic activity. Although PBP2a and PBP2 were also among the most succinylated proteins in the MRSA proteome, peptidoglycan architecture and cross-linking were unchanged in the sucC mutant. These data reveal that perturbation of the MRSA succinylome impacts two interconnected cell wall phenotypes, leading to repression of autolytic activity and increased susceptibility to β-lactam antibiotics.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Nyckelord
- Antibiotic resistance
- Beta-lactams
- MRSA
- Succinyl-CoA
- Succinylome
- TCA cycle
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Campbell, Christ ...
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Fingleton, Clair ...
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Zeden, Merve S.
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Bueno, Emilio
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Gallagher, Laura ...
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Shinde, Dhananja ...
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visa fler...
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Ahn, Jongsam
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Olson, Heather M ...
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Fillmore, Thomas ...
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Adkins, Joshua N ...
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Razvi, Fareha
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Bayles, Kenneth ...
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Fey, Paul D.
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Thomas, Vinai C.
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Cava, Felipe
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Clair, Geremy C.
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O’gara, James P.
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