Ironing Out the Unconventional Mechanisms of Iron Acquisition and Gene Regulation in Chlamydia

Abstract

The obligate intracellular pathogen Chlamydia trachomatis, along with its close species relatives, is known to be strictly dependent upon the availability of iron. Deprivation of iron in vitro induces an aberrant morphological phenotype termed “persistence.” This persistent phenotype develops in response to various immunological and nutritional insults and may contribute to the development of sub-acute Chlamydia-associated chronic diseases in susceptible populations. Given the importance of iron to Chlamydia, relatively little is understood about its acquisition and its role in gene regulation in comparison to other iron-dependent bacteria. Analysis of the genome sequences of a variety of chlamydial species hinted at the involvement of unconventional mechanisms, being that Chlamydia lack many conventional systems of iron homeostasis that are highly conserved in other bacteria. Herein we detail past and current research regarding chlamydial iron biology in an attempt to provide context to the rapid progress of the field in recent years. We aim to highlight recent discoveries and innovations that illuminate the strategies involved in chlamydial iron homeostasis, including the vesicular mode of acquiring iron from the intracellular environment, and the identification of a putative iron-dependent transcriptional regulator that is synthesized as a fusion with a ABC-type transporter subunit. These recent findings, along with the noted absence of iron-related homologs, indicate that Chlamydia have evolved atypical approaches to the problem of iron homeostasis, reinvigorating research into the iron biology of this pathogen.

The iron-dependent repressor YtgR regulates the tryptophan salvage pathway through a bipartite mechanism of transcriptional control inChlamydia trachomatis

“…However, omcB expression was 203 significantly induced following 12 hrs of Bpdl-treatment (p = 0.00015). This was 204 unexpected, but we note that omcB expression has been shown to vary between 205 chlamydial serovars and species when starved for iron (Pokorzynski et al, 2017). 206…”

Interactions Screenings Unearth Potential New Divisome Components in the Chlamydia-Related Bacterium, Waddlia chondrophila

“…Deletion of SufD abolishes Suf function in vivo and reduces bacteria survival [56]. Iron deprivation in C. trachomatis blocks division and induces formation of aberrant bodies [57].…”

Genome-wide transcriptional responses of iron-starvedChlamydia trachomatisreveal prioritization of metabolic precursor synthesis over protein translation

“…Induction of inflammatory cytokines such as IFN-g and IL-6 in response to chlamydial infection likely causes sequestration of free iron by the mononuclear phagocytic system, which includes both cellular and systemic regulatory pathways (20–27). Readers are referred to two comprehensive reviews of the coordinated regulation of iron homeostasis by systemic and cellular mechanisms (26, 28).…”

“…The C-terminus of the YtgC permease, referred to as YtgR, is homologous to the Cornyebacterium repressor DtxR, and has been recently characterized as an iron-dependent repressor of the ytgABCD iron-acquisition operon (42). A recent review highlights the differences between iron-acquisition strategies of Chlamydia with other intracellular bacteria (27).…”