The disruption of prenylation leads to pleiotropic rearrangements in cellular behavior in Staphylococcus aureus
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Summary: Prenylation is the addition of prenyl groups to peptide chains or metabolites via the condensation of geranyl‐ or isopentenyl‐diphosphate moieties by geranyltranstransferases. Although this process is extensively studied in eukaryotes, little is known about the influence of prenylation in prokaryotic species. To explore the role of this modification in bacteria, we generated a mutation in the geranyltranstransferase (I sp A) of Staphylococcus aureus. Quite strikingly, the ispA mutant completely lacked pigment and exhibited a previously undescribed small colony variant‐like phenotype. Further pleiotropic defects in cellular behavior were noted, including impaired growth, decreased ATP production, increased sensitivity to oxidative stress, increased resistance to aminoglycosides and cationic antimicrobial peptides, and decreased resistance to cell wall‐targeting antibiotics. These latter effects appear to result from differences in envelope composition as ispA mutants have highly diffuse cell walls (particularly at the septum), marked alterations in fatty acid composition and increased membrane fluidity. Taken together, these data present an important characterization of prokaryotic prenylation and demonstrate that this process is central to a wealth of pathways involved in mediating cellular homeostasis in S. aureus.
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Other enzymes such as MprF, PG synthase (PgsA), cyclic fatty acid synthase (Cfa) and geranyltransferase involved in CM phospholipid homeostasis have also been linked to DAP-R.
“Other enzymes such as MprF, PG synthase (PgsA), cyclic fatty acid synthase (Cfa) and geranyltransferase (98) involved in CM phospholipid homeostasis have also been linked to DAP-R.”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [98]
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- Authors
- Krute, C. N., Carroll, R. K., Rivera, F. E., Weiss, A., Young, R. M., Shilling, A., Botlani, M., Varma, S., Baker, B. J., & Shaw, L. N.
- Affiliations
- University of South Florida (US)
- Ohio University (US)
- Corresponding author
- Shaw, Lindsey N.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2015-01-16
- Volume
- 95
- Issue
- 5
- Pages
- 819-832
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- PMC
- PMC11915216
- OpenAlex
- W1892837989
- Cited by
- 17
- References
- 62
- Citations by year
- 2026: 1 · 2025: 2 · 2022: 2 · 2021: 1 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 4
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI080626)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Keywords
- prenylation, ISPA, Staphylococcus aureus, pleiotropic phenotypes, small colony variants, bacterial pigments, oxidative stress resistance, aminoglycoside resistance, antimicrobial peptide resistance, cell wall composition, membrane fluidity, fatty acid composition, ATP production, bacterial cell envelope
- MeSH terms
- Cell Wall, Fatty Acids, Membrane Fluidity, Microbial Sensitivity Tests, Mutation, Phenotype, Staphylococcus aureus, Protein Prenylation, Gene Expression Profiling, Antimicrobial Cationic Peptides, Drug Resistance, Bacterial, Geranyltranstransferase
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