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

Abstract

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.

The AlternativeTranslational Profile That Underlies the Immune-Evasive State of Persistence in Chlamydiaceae Exploits Differential Tryptophan Contents of the Protein Repertoire

“…This is the prime source of carbon and energy for Chlamydiaceae (60), which lack the ability to import glucose and which further lack hexokinase. It is of interest in this context that persistence can be triggered by manipulation of glucose availability to host cells in a tissue culture system (46).…”

Herpes simplex virus co-infection-induced Chlamydia trachomatis persistence is not mediated by any known persistence inducer or anti-chlamydial pathway

“…Global deprivation of amino acids and other nutrients, especially iron and glucose, can also cause developing chlamydiae to enter persistence (Harper et al, 2000;Raulston, 1997). To investigate the possibility that HSV-2 co-infection induces chlamydial persistence by limiting iron availability, we first determined whether co-infected cells were iron-deprived.…”

“…Interestingly, persistent chlamydiae can re-enter the normal developmental cycle and recover infectivity if the environmental stressor is removed. For example, nutrient-deprived, persistent chlamydiae resume development into infectious EBs if the appropriate nutrients are replenished (Harper et al, 2000;Matsushima et al, 1999;Raulston, 1997).…”

A small-molecule compound belonging to a class of 2,4-disubstituted 1,3,4-thiadiazine-5-ones inhibits intracellular growth and persistence of Chlamydia trachomatis

“…Research from multiple teams has demonstrated that an encounter with specific stimuli can transform Chlamydia into a third state called 'persistence' (Clark et al, 1982;Harper et al, 2000), which has been defined as a reversible interruption of productive intracellular chlamydial growth mediated by environmental factors (Beatty et al, 1994). Persistence is an alternative outcome of a productive bacterial infection where a subpopulation of the bacteria becomes 'invisible' in response to prolonged antibiotic treatment, warding off innate and adaptive immune responses, causing little or no symptoms in the infected host, and possibly unnoticed by the diagnostician (Bavoil et al, 2000).…”