Many intracellular pathogens rely on host cell membrane compartments for their survival. The strategies they have developed to subvert intracellular trafficking are often unknown, and SNARE proteins, which are essential for membrane fusion, are possible targets. The obligate intracellular bacteria Chlamydia replicate within an intracellular vacuole, termed an inclusion. A large family of bacterial proteins is inserted in the inclusion membrane, and the role of these inclusion proteins is mostly unknown. Here we identify SNARE-like motifs in the inclusion protein IncA, which are conserved among most Chlamydia species. We show that IncA can bind directly to several host SNARE proteins. A subset of SNAREs is specifically recruited to the immediate vicinity of the inclusion membrane, and their accumulation is reduced around inclusions that lack IncA, demonstrating that IncA plays a predominant role in SNARE recruitment. However, interaction with the SNARE machinery is probably not restricted to IncA as at least another inclusion protein shows similarities with SNARE motifs and can interact with SNAREs. We modelled IncA's association with host SNAREs. The analysis of intermolecular contacts showed that the IncA SNARE-like motif can make specific interactions with host SNARE motifs similar to those found in a bona fide SNARE complex. Moreover, point mutations in the central layer of IncA SNARE-like motifs resulted in the loss of binding to host SNAREs. Altogether, our data demonstrate for the first time mimicry of the SNARE motif by a bacterium.
Chlamydiae are obligate intracellular bacteria that have co-evolved with eukaryotic cells and adapted to a wide range of hosts, causing several diseases in humans and animals. For example, one species pathogenic to humans, Chlamydia trachomatis, is the leading cause of preventable blindness and of bacterial sexually transmitted diseases worldwide. Chlamydiae multiply inside a membrane-bound compartment, the inclusion. The exchanges between the membrane of the inclusion and other intracellular membranes are tightly controlled by the bacteria, for example avoiding fusion with some degradation compartments, while acquiring lipids. Inclusion proteins, made by the bacteria and secreted into the inclusion membrane, are thought to play a central role in controlling these interactions, although their exact function is mostly unknown. We have identified, in three inclusion proteins, a motif common to proteins that are essential for the fusion of two compartments in eukaryotic cells, the SNARE proteins. Via this motif, inclusion proteins interact specifically with a subset of SNAREs of the host, which leads to the selective recruitment of intracellular compartments around the inclusion. This study thus provides a striking example of mimicry of the host by an intracellular pathogen.