Chlamydial metabolism revisited: interspecies metabolic variability and developmental stage-specific physiologic activities

Abstract

Chlamydiae are a group of obligate intracellular bacteria comprising important human and animal pathogens as well as symbionts of ubiquitous protists. They are characterized by a developmental cycle including two main morphologically and physiologically distinct stages, the replicating reticulate body and the infectious nondividing elementary body. In this review, we reconstruct the history of studies that have led to our current perception of chlamydial physiology, focusing on their energy and central carbon metabolism. We then compare the metabolic capabilities of pathogenic and environmental chlamydiae highlighting interspecies variability among the metabolically more flexible environmental strains. We discuss recent findings suggesting that chlamydiae may not live as energy parasites throughout the developmental cycle and that elementary bodies are not metabolically inert but exhibit metabolic activity under appropriate axenic conditions. The observed host-free metabolic activity of elementary bodies may reflect adequate recapitulation of the intracellular environment, but there is evidence that this activity is biologically relevant and required for extracellular survival and maintenance of infectivity. The recent discoveries call for a reconsideration of chlamydial metabolism and future in-depth analyses to better understand how species- and stage-specific differences in chlamydial physiology may affect virulence, tissue tropism, and host adaptation.

Keywords: Chlamydia; Parachlamydia; Protochlamydia; developmental cycle; genomics; metabolism.

Figure 1. Diversity of the Chlamydiae

The phylogenetic tree shows the relationship of pathogenic chlamydiae (Chlamydiaceae) with other families collectively referred to as environmental chlamydiae. Representative species are shown, and their genome sizes relative to the 3.1 Mb genome of Parachlamydia acanthamoebae are indicated as pie charts. Note that the names Parilichlamydiaceae and Actinochlamydiaceae were independently proposed for what might represent a single family, here indicated as Parilichlamydiaceae (Horn, 2008, Steigen, et al., 2013, Stride, et al., 2013). The unrooted tree is a based on a recent survey of chlamydial diversity in metagenomic and amplicon datasets (Lagkouvardos, et al., 2013).

Figure 2. The chlamydial developmental cycle

The Chlamydia trachomatis developmental cycle is depicted here with approximate times indicated for an LGV strain. Other strains or species grow at different rates. Infection is intiated by the attachment and internalization of an EB which remains within a non-fusogenic vesicle known as the inclusion. Once committed to development, Chlamydia EBs rapidly lose infectivity; one of the first indications of their differentiation to RBs. C. trachomatis EBs increase in size as they differentiate to RBs over the first 10 – 12 h before they initiate multiplication. After about 18 h (for the LGV strains, longer for ocular and genital strains of C. trachomatis and other chlamydial species), the RBs continue to multiply even as a sub-set asynchronously begins to differentiate back to EBs, which accumulate within the inclusion until release by lysis or extrusion at around 48 h or later.

Figure 3. The extended metabolic repertoire of environmental chlamydiae

Selected metabolic features of environmental chlamydiae compared to the Chlamydiaceae as inferred from genome sequences are shown. Pathway reconstructions are based on data from (Horn, et al., 2004, Bertelli, et al., 2010, Collingro, et al., 2011).