Chlamydia trachomatis growth and development requires the activity of host Long-chain Acyl-CoA Synthetases (ACSLs)

Maria A. Recuero-Checa, Manu Sharma, Constance Lau, Paul A. Watkins, Charlotte A. Gaydos, Deborah Dean

Research output: Contribution to journalArticle

Abstract

The obligate-intracellular pathogen Chlamydia trachomatis (Ct) has undergone considerable genome reduction with consequent dependence on host biosynthetic pathways, metabolites and enzymes. Long-chain acyl-CoA synthetases (ACSLs) are key host-cell enzymes that convert fatty acids (FA) into acyl-CoA for use in metabolic pathways. Here, we show that the complete host ACSL family [ACSL1 and ACSL3-6] translocates into the Ct membrane-bound vacuole, termed inclusion, and remains associated with membranes of metabolically active forms of Ct throughout development. We discovered that three different pharmacologic inhibitors of ACSL activity independently impede Ct growth in a dose-dependent fashion. Using an FA competition assay, host ACSLs were found to activate Ct branched-chain FAs, suggesting that one function of the ACSLs is to activate Ct FAs and host FAs (recruited from the cytoplasm) within the inclusion. Because the ACSL inhibitors can deplete lipid droplets (LD), we used a cell line where LD synthesis was switched off to evaluate whether LD deficiency affects Ct growth. In these cells, we found no effect on growth or on translocation of ACSLs into the inclusion. Our findings support an essential role for ACSL activation of host-cell and bacterial FAs within the inclusion to promote Ct growth and development, independent of LDs.

Original languageEnglish (US)
Article number23148
JournalScientific Reports
Volume6
DOIs
StatePublished - Mar 18 2016

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Coenzyme A Ligases
Acyl Coenzyme A
Chlamydia trachomatis
Lipid Droplets
Fatty Acids
Membranes
Enzymes
Vacuoles
Metabolic Networks and Pathways
Cytoplasm
Genome
Cell Line

ASJC Scopus subject areas

  • General

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Chlamydia trachomatis growth and development requires the activity of host Long-chain Acyl-CoA Synthetases (ACSLs). / Recuero-Checa, Maria A.; Sharma, Manu; Lau, Constance; Watkins, Paul A.; Gaydos, Charlotte A.; Dean, Deborah.

In: Scientific Reports, Vol. 6, 23148, 18.03.2016.

Research output: Contribution to journalArticle

Recuero-Checa, Maria A.; Sharma, Manu; Lau, Constance; Watkins, Paul A.; Gaydos, Charlotte A.; Dean, Deborah / Chlamydia trachomatis growth and development requires the activity of host Long-chain Acyl-CoA Synthetases (ACSLs).

In: Scientific Reports, Vol. 6, 23148, 18.03.2016.

Research output: Contribution to journalArticle

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