2020
DOI: 10.1128/mbio.03027-20
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The Bactericidal Fatty Acid Mimetic 2CCA-1 Selectively Targets Pneumococcal Extracellular Polyunsaturated Fatty Acid Metabolism

Abstract: Streptococcus pneumoniae, a major cause of pneumonia, sepsis, and meningitis worldwide, has the nasopharynges of small children as its main ecological niche. Depletion of pneumococci from this niche would reduce the disease burden and could be achieved using small molecules with narrow-spectrum antibacterial activity. We identified the alkylated dicyclohexyl carboxylic acid 2CCA-1 as a potent inducer of autolysin-mediated lysis of S. pneumoniae, while having low activity against Staphylococcus aureus. 2CCA-1-r… Show more

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Cited by 2 publications
(2 citation statements)
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References 57 publications
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“…Interestingly, FabT represses the expression of two non-FASII genes involved in FA and phospholipid metabolism. i-fakB3 encodes FakB3, which is involved in the incorporation of polyunsaturated FAs, which are not synthesized by Firmicutes (22,23); and ii-plsC encodes PlsC, which catalyzes joining of a second FA to the 1-acyl-sn-glycerol 3-phosphate (bearing a single FA) to complete phospholipid acylation. S. pneumoniae FabT thus couples regulation of FA and phospholipid synthesis, similar to FapR regulation in B. subtilis and Staphylococcus aureus, where the regulatory mechanisms are different (24,25).…”
Section: Non-fasii Gene Regulation By the Fabt Repressormentioning
confidence: 99%
See 1 more Smart Citation
“…Interestingly, FabT represses the expression of two non-FASII genes involved in FA and phospholipid metabolism. i-fakB3 encodes FakB3, which is involved in the incorporation of polyunsaturated FAs, which are not synthesized by Firmicutes (22,23); and ii-plsC encodes PlsC, which catalyzes joining of a second FA to the 1-acyl-sn-glycerol 3-phosphate (bearing a single FA) to complete phospholipid acylation. S. pneumoniae FabT thus couples regulation of FA and phospholipid synthesis, similar to FapR regulation in B. subtilis and Staphylococcus aureus, where the regulatory mechanisms are different (24,25).…”
Section: Non-fasii Gene Regulation By the Fabt Repressormentioning
confidence: 99%
“…Investigation of its bactericidal effect led to the isolation of resistant mutants (23). One mutation mapped to fakB3, encoding a FA binding protein involved in the uptake of polyunsaturated FAs.…”
Section: Fabt and Bacterial Physiologymentioning
confidence: 99%