Host cell death during infection with Chlamydia: a double-edged sword.

Barbara S Sixt

doi:10.1093/femsre/fuaa043

Abstract

ABSTRACTThe phylum Chlamydiae constitutes a group of obligate intracellular bacteria that infect a remarkably diverse range of host species. Some representatives are significant pathogens of clinical or veterinary importance. For instance, Chlamydia trachomatis is the leading infectious cause of blindness and the most common bacterial agent of sexually transmitted diseases. Chlamydiae are exceptionally dependent on their eukaryotic host cells as a consequence of their developmental biology. At the same time, host cell death is an integral part of the chlamydial infection cycle. It is therefore not surprising that the bacteria have evolved exquisite and versatile strategies to modulate host cell survival and death programs to their advantage. The recent introduction of tools for genetic modification of Chlamydia spp., in combination with our increasing awareness of the complexity of regulated cell death in eukaryotic cells, and in particular of its connections to cell-intrinsic immunity, has revived the interest in this virulence trait. However, recent advances also challenged long-standing assumptions and highlighted major knowledge gaps. This review summarizes current knowledge in the field and discusses possible directions for future research, which could lead us to a deeper understanding of Chlamydia’s virulence strategies and may even inspire novel therapeutic approaches.

Highlights

The phylum Chlamydiae is a group of obligate intracellular bacteria that infect a wide range of host species, including members of all major groups of vertebrates, as well as invertebrates, and even unicellular eukaryotes (Horn 2008)
Contrasting with the results reported for human cells, in mouse embryonic fibroblasts (MEFs), MCL1 deficiency only caused a mild sensitization to STSinduced apoptosis (Ying et al 2008a)
While it is clear that late stage host cell death is an exit strategy that promotes Chlamydia spread to formerly uninfected cells, the molecular mechanisms that regulate this important event in Chlamydia’s infection cycle remain obscure

Summary

Introduction

The phylum Chlamydiae is a group of obligate intracellular bacteria that infect a wide range of host species, including members of all major groups of vertebrates, as well as invertebrates, and even unicellular eukaryotes (Horn 2008). Chlamydia trachomatis (serovars D–K) is the most frequent bacterial agent of sexually transmitted diseases and as such a significant cause of infertility and adverse pregnancy outcomes (Newman et al 2015). The second major human pathogenic Chlamydia species, Received: 30 June 2020; Accepted: 2 September 2020 C The Author(s) 2020.

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