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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 (<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>sp<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>) of <jats:styled-content style=\"fixed-case\"><jats:italic>S<\/jats:italic><\/jats:styled-content><jats:italic>taphylococcus\u2009aureus<\/jats:italic>. Quite strikingly, the <jats:italic>isp<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>A<\/jats:italic><\/jats:styled-content> mutant completely lacked pigment and exhibited a previously undescribed small colony variant\u2010like phenotype. Further pleiotropic defects in cellular behavior were noted, including impaired growth, decreased <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> production, increased sensitivity to oxidative stress, increased resistance to aminoglycosides and cationic antimicrobial peptides, and decreased resistance to cell wall\u2010targeting antibiotics. These latter effects appear to result from differences in envelope composition as <jats:italic>isp<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>A<\/jats:italic><\/jats:styled-content> 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 <jats:styled-content style=\"fixed-case\"><jats:italic>S<\/jats:italic><\/jats:styled-content><jats:italic>.\u2009aureus<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/mmi.12900","type":"journal-article","created":{"date-parts":[[2014,12,10]],"date-time":"2014-12-10T09:41:43Z","timestamp":1418204503000},"page":"819-832","source":"Crossref","is-referenced-by-count":17,"title":["The disruption of prenylation leads to pleiotropic rearrangements in cellular behavior in <scp><i>S<\/i><\/scp><i>taphylococcus aureus<\/i>"],"prefix":"10.1111","volume":"95","author":[{"given":"Christina N.","family":"Krute","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Microbiology &amp; Molecular Biology University of South Florida  Tampa FL 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