Lipid Synthesis by Isolated Chlamydia psittaci

Abstract

The isolated cells of the host-dependent meningopneumonitis agent, Chlamydia psittaci, were shown to incorporate radioactive carbon from aspartate, isoleucine, and glucose-6-phosphate into cell lipids. The nature of this incorporation was investigated. Radioactivity was found only in the fatty acids and primarily in the phosphatidyl ethanolamine, and, to a lesser extent, in the phosphatidyl choline fractions. Branched-chain fatty acids, not found in host lipid, were shown to constitute a large proportion of the fatty acid content of phosphatidyl ethanolamine. The reasons why only fatty acid synthesis took place under the conditions of our experiments with isolated meningopneumonitis agent cells remain obscure.

Interaction of chlamydiae and host cells in vitro.

“…The composition of chlamydial lipids has been reviewed elsewhere (326). Of particular interest to a discussion of the biosynthesis of chlamydial lipids is the presence in chlamydiae of lipids not found in their host cells, notably the C 15:0 and C 17:0 anteiso branched-chain fatty acids and phosphatidyl glycerol (126,127,140,205,269,326). It is hard to follow the biosynthesis of chlamydial lipids inside of host cells because the chlamydiae do not make nearly as much lipid as their hosts and because they progressively inhibit host lipid synthesis as the infection proceeds.…”

“…When [3H]isoleucine is used to label newly synthesized branched-chain fatty acids and phospho-lipids, the synthesis of lipids in infected L cells increases from 12 h after infection to a maximum at 25 to 30 h that is 100 times the rate in cycloheximide-treated, uninfected L cells (373). Host-free mixtures of RBs and EBs prepared from allantoic fluid from C. psittaci-infected chicken embryos incorporate the carbon of labeled aspartate, isoleucine, and glucose-6-phosphate into trichloroacetic acid-insoluble fractions, and almost all the label appears in the branched-chain fatty acids of phosphatidyl ethanolamine and phosphatidyl choline (140,511). The incorporation of aspartate and isoleucine depends on the presence of exogenous ATP, and the uptake of glucose-6-phosphate, the best label of the three, is stimulated by it (511).…”

N-Acylated Derivatives of Sulfamethoxazole Block Chlamydia Fatty Acid Synthesis and Interact with FabF

“…The amino acids valine, leucine, and isoleucine are precursors to isobutyryl-CoA, isovaleryl-CoA, and 2-methylbutyryl-CoA, which are generated by the bacterial enzyme ␣-keto acid dehydrogenase and incorporated into Chlamydia-specific branched-chain fatty acids by 3-oxoacyl-ACP synthase III (FabH). Thus, lipids synthesized by C. trachomatis can be detected by incubation of Chlamydia-infected cells with radiolabeled valine, leucine, or isoleucine followed by total lipid extraction and monitoring of the increase in radioactivity in this fraction compared to that for control uninfected cells (11,25,26). Of these three amino acids, isoleucine has previously been reported to show the most extensive incorporation into Chlamydia branched-chain fatty acids (25).…”

The chlamydia: molecular biology of procaryotic obligate parasites of eucaryocytes.

“…A branched-chain anteiso 15:0 fatty acid was synthesized in LGVinfected cells and was not present in uninfected cells. Three branched-chain fatty acids were found in C. psittaci (33,82). More recently, Fan and Jenkin (29) showed that the LGV agent could divert phosphotidic acid synthesis in the host cell for the formation of its own major phospholipid (phosphatidyl ethanolamine).…”