Abstract
During infection chlamydial pathogens form an intracellular membrane-bound replicative niche termed the inclusion, which is enriched with bacterial transmembrane proteins called Incs. Incs bind and manipulate host cell proteins to promote inclusion expansion and provide camouflage against innate immune responses. Sorting nexin (SNX) proteins that normally function in endosomal membrane trafficking are a major class of inclusion-associated host proteins, and are recruited by IncE/CT116. Crystal structures of the SNX5 phox-homology (PX) domain in complex with IncE define the precise molecular basis for these interactions. The binding site is unique to SNX5 and related family members SNX6 and SNX32. Intriguingly the site is also conserved in SNX5 homologues throughout evolution, suggesting that IncE captures SNX5-related proteins by mimicking a native host protein interaction. These findings thus provide the first mechanistic insights both into how chlamydial Incs hijack host proteins, and how SNX5-related PX domains function as scaffolds in protein complex assembly.
Highlights
To counter host defence mechanisms intracellular bacterial pathogens have evolved numerous strategies to evade immune detection, replicate and cause infection
It was previously shown that the sorting nexins SNX1, SNX2, SNX5 and SNX6 are recruited to the inclusion membrane in C. trachomatis infected cells (Aeberhard et al, 2015; Mirrashidi et al, 2015)
To confirm the role of inclusion protein (IncE) in direct SNX5 protein recruitment to the chlamydial inclusion we examined the localisation of GFP-tagged SNX5 in HeLa cells infected with C. trachomatis L2 (CTL2) for 24 hr (MOI ~0.5)
Summary
To counter host defence mechanisms intracellular bacterial pathogens have evolved numerous strategies to evade immune detection, replicate and cause infection. The pathogen often endeavors to decorate the PCV with host proteins and lipids that mimic other host cell organelles in order to circumvent innate immune detection, expand the replicative niche and acquire nutrients to support intracellular replication (Di Russo Case and Samuel, 2016; Personnic et al, 2016). This process is often orchestrated through the action of molecular syringe-like secretion systems that deliver bacterial effector proteins directly into the host cell cytoplasm. Even though chlamydial infections can generally be treated with antibiotics, persistent infections remain a challenge (Kohlhoff and Hammerschlag, 2015; Mpiga and Ravaoarinoro, 2006)
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