Competitive inhibition of amino acid uptake suppresses chlamydial growth: Involvement of the chlamydial amino acid transporter BrnQ

Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany, Department of Biological Sciences, University of Jordan, Amman, Jordan, Department of Pediatrics, Charité University Medical Center, Berlin, Germany, Institute of Biology, Humboldt Universität zu Berlin, Berlin, Germany

^* To whom correspondence should be addressed. Email: meyer{at}mpiib-berlin.mpg.de.

	Abstract

Chlamydiaceae are obligate intracellular bacterial pathogens that strictly depend on host metabolites, such as nucleotides, lipids, and amino acids. Depletion of amino acids from cell culture media causes abnormal chlamydial development in vitro. Surprisingly, enrichment of certain amino acids also retards chlamydial growth. Our experiments revealed that these anti-chlamydial effects are largely independent of changes in the host cell transcriptome or proteome, as well as in the major signal transduction pathway modulated by amino acids, the mTOR (mammalian target of rapamycin) pathway. Furthermore, chlamydial growth inhibition induced by leucine, isoleucine, methionine or phenylalanine was completely reversed by the concomitant addition of valine. In contrast, growth inhibition induced by serine, glycine or threonine was not reversed by valine addition. The functional characterization of the only predicted chlamydial transporter for branched-chain amino acids, BrnQ, revealed that it can be blocked by leucine, isoleucine, methionine or phenylalanine, but not by serine, glycine or threonine. This chlamydial transporter is the only known BrnQ homolog possessing specificity for methionine, suggesting a unique strategy for methionine uptake among gram-negative bacteria. The anti-chlamydial effects of leucine, isoleucine, methionine and phenylalanine could be explained as competitive inhibition of the BrnQ transporter and subsequent valine starvation.