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Infection and Immunity, March 2000, p. 1457-1464, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Chlamydial Development Is Adversely Affected by Minor Changes in Amino Acid Supply, Blood Plasma Amino Acid Levels, and Glucose Deprivation

Angela Harper,1,* Christopher I. Pogson,2 Meirion L. Jones,1 and John H. Pearce1

Microbial Molecular Genetics and Cell Biology Group, School of Biological Sciences, University of Birmingham, Birmingham B15 2TT,1 and Biochemical Sciences, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS,2 United Kingdom

Received 5 October 1999/Returned for modification 3 November 1999/Accepted 15 December 1999

This study has demonstrated the extreme sensitivity of Chlamydia trachomatis growing in McCoy cells to small changes in external amino acid supply. In the absence of cycloheximide, a decrease in the amino acid concentration of medium to 75% of control values was sufficient to induce the growth of enlarged chlamydial forms of reduced infectivity. Morphology became more distorted and the yield of infectious particles from inclusions declined as medium amino acid levels were further reduced. These events correlated with a general decline in intracellular amino acids, as measured by high-performance liquid chromatography, suggesting that chlamydiae require a minimum concentration of each amino acid for normal development. Cycloheximide enhanced the production of normal organisms and increased infectivity yield in media, suggesting that the drug increased the available pool of amino acids. This was supported by intracellular amino acid analyses. Aberrant forms with reduced infectivity were also induced during supply of infected cell cultures with medium containing blood plasma amino acid concentrations, supporting the proposal that nutrient levels in vivo could promote abnormal chlamydial development. Markedly abnormal forms were also observed during glucose deprivation, providing further evidence that aberrant development is a general stress-related response.

* Corresponding author. Present address: Department of Clinical Chemistry, Birmingham Children's Hospital, Whittall St., Birmingham B4 6NL, United Kingdom. Phone: 44 (0)121 333 9877. Fax: 44 (0)121 333 9911. E-mail: Angela.Harper{at}southroad.freeserve.co.uk.

Infection and Immunity, March 2000, p. 1457-1464, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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