Low-nutrient induction of abnormal chlamydial development: A novel component of chlamydial pathogenesis?

Abstract

The intracellular development of chlamydiae in McCoy cells incubated in Eagle's minimal essential medium lacking all 13 amino acids was examined both by fluorescence and electron microscopy and by infectivity titration. Aberrant development occurred in almost all inclusions of strains of Chlamydia trachomatis and C. psittaci with the production of abnormal forms which differed in size, shape and internal structure from normal reticulate and elementary body forms. Detailed analysis of the response of C. trachomatis L2 strain 434 to graded reductions in amino acid level showed that infectivity was reduced and morphological abnormality increased as amino acid concentrations were lowered from 33 to 0% of amino acids present in minimal essential medium. Reversion of inclusions to normal and reappearance of infectious forms occurred on restoration of amino acids and further incubation. It is suggested that aberrant development may account for the presence in vivo of non-cultivable chlamydiae and that such development can arise via tryptophan deprivation mediated by local release of interferon gamma.

Antimicrobial Treatment of Multiple Sclerosis

“…Survival in this form may depend upon a nonoxidative metabolic pathway [9]. The finding that Chlamydiae enter the cryptic form when starved of amino acids [10] lends support to the idea of persistence being a stringent response. Such a transformation may occur naturally during untreated infection as interferon-gamma (IFN-c) is produced by the host in an attempt to curtail intracellular infection (reviewed by Rottenburg et al) [11] IFN-c has been shown to induce persistence in C. pneumoniae in vitro by means of host-cell mechanisms which reduce the availability of intracellular tryptophan [12,13].…”

Divergent modulation of Chlamydia pneumoniae infection cycle in human monocytic and endothelial cells by iron, tryptophan availability and interferon gamma

“…The molecular mechanisms required for chlamydial differentiation are poorly defined because of the lack of traceable genetic system. Chlamydia fail to complete their developmental cycle when starved for nutrients such as amino acids and iron (Coles et al, 1993;Raulston, 1997) or when exposed to antibiotics like penicillin. Under these conditions Chlamydia strains enter a semidormant state.…”

Analysis of Chlamydia pneumoniae infection in mononuclear cells by reverse transcription-PCR targeted to chlamydial gene transcripts

“…In vitro persistent chlamydial infection can be induced by nutrient and iron depletion or by exposure to certain antibiotics or cytokines [14,[16][17][18][19]. Spontaneous development of a persistent infection in cell culture without external induction has also been described [20,21].…”