A Decrease in Fatty Acid Synthesis Rescues Cells with Limited Peptidoglycan Synthesis Capacity

Abstract

Understanding how a bacterium coordinates cell envelope synthesis is essential to fully appreciate how bacteria grow, divide, and resist cell envelope stresses, such as β-lactam antibiotics. Balanced synthesis of the peptidoglycan cell wall and the cell membrane is critical for cells to maintain shape and turgor pressure and to resist external cell envelope threats.

RfaA (YqhY), a novel adaptor protein, controls metabolite-sensitive protein degradation in Bacillus subtilis

“…2B). In agreement with previous studies 16,26 , we found that branched-chain C15 and C17 fatty acids account for the majority of the fatty acid pool in the wild type strain, whereas palmitic acid (C16) corresponds to only about 10%. Of the branched fatty acids, the C15 species was predominant as compared to the C17 species (C17-C15 ratio of 0.53).…”

“…In agreement with our earlier observations, growth of the rfaA mutant GP1468 in the absence of glutamate was severely compromised. As expected and in agreement with published data 16 , the inhibition of fatty acid biosynthesis by increasing concentrations of cerulenin resulted in a growth inhibition for the wild type strain. In contrast, growth of the rfaA mutant was rescued in the presence of a low concentration of cerulenin (2 µg/ml), and even at 5 µg/ml, the growth was better as compared to the absence of the inhibitor.…”

“…If the observed accumulation of lipids in the rfaA mutant in the absence of glutamate would be the growth-inhibiting problem, one would expect that the inhibition of lipid biosynthesis might restore growth of the mutant in the absence of glutamate. To address this idea, we made use of cerulenin, an inhibitor of fatty acid synthesis that binds β-ketoacyl-ACP synthases, such as FabF, FabHA and FabHB 16,24,25 (see Fig. 1C).…”

“…In most cases, the membranes consist of phospholipids with fatty acids as a major building block and integrated proteins. To assure integrity of the cell, the synthesis of the cell envelope has to be tightly controlled and needs to be coupled to the supply of building blocks from central metabolism 14,15,16 . This is easily achieved with respect to the availability of carbon sources as acetyl-CoA and glycerol-3-phosphate both derived from glycolysis are the major precursors for lipid biosynthesis.…”

RfaA (YqhY), a novel adaptor protein, controls metabolite-sensitive protein degradation in Bacillus subtilis

“…7 If the observed accumulation of lipids in the rfaA mutant in the absence of glutamate would be the growth-inhibiting problem, one would expect that the inhibition of lipid biosynthesis might restore growth of the mutant in the absence of glutamate. To address this idea, we made use of cerulenin, an inhibitor of fatty acid synthesis that binds β-ketoacyl-ACP synthases, such as FabF, FabHA and FabHB 16,24,25 (see Fig. 1C).…”