SCAN: Type III secretion tricks in Yersinia, Salmonella, and Chlamydia

ABSTRACT

Type III secretion (T3S) is a mechanism used by several Gram-negative pathogenic and symbiotic bacteria to deliver effector proteins directly from the bacterial cytoplasm into the cytosol and membranes of eukaryotic host cells. The effectors manipulate the eukaryotic cell to benefit the bacteria. In this talk, I will present an overview on T3S in pathogenic bacteria, from the functioning of the secretion-translocation machine to the intracellular role of the effectors. I will focus in studies made in Yersinia and Salmonella, which can cause systemic (plague and typhoid fever) or gastrointestinal diseases in humans. To finalise, I will briefly show how in the Infecion Biology laboratory we intend to use Yersinia and Salmonella to study the secretion and function of T3S effectors of Chlamydia trachomatis, an obligate intracellular bacterium, intractable to genetic manipulation, which is the most frequent bacterial cause of sexually transmitted diseases and of preventable blindness worldwide.

Many T3S nanomachines (injectisomes) possess a stiff needle-like structure of a defined length. The needle is thought to function as the conduit for protein translocation. I will present data showing that a minimal needle length is required for efficient functioning of the Yersinia enterocolitica injectisome. This minimal needle length correlates with the length of the major adhesin at the bacterial surface. This suggests that the needle may be required for triggering T3S and its length may have evolved to match specific structures at the bacterial and host cell surfaces.

Salmonella enterica are facultative intracellular bacteria that multiply intracellularly in a membrane-bound vacuole. The intracellular replication of Salmonella is dependent in the manipulation of host cell membrane trafficking by T3S effectors. Salmonella effectors were typically known to manipulate the endocytic pathway. In epithelial cells, this results in the formation of membrane tubules enriched in late endocytic proteins. We recently found that Salmonella effectors can also subvert specific post-Golgi trafficking and that this is reflected in the formation of a distinct tubular network. Hijacking of post-Golgi trafficking could be a means for the bacteria to acquire nutrients and membrane and suggest a new mechanism by which Salmonella effectors might control host immune responses.