Structural Determinants ofHaemophilus influenzaeAdherence to Host Epithelia: Variations on Type V Secretion

Abstract

This chapter focuses on Hap, the HMW1/HMW2 adhesins, and the Hia/Hsf adhesins. All of these adhesive proteins are grouped in the type V secretion pathway, which includes the autotransporter pathway and the two-partner secretion (TPS) pathway. Hap is ubiquitous among Haemophilus influenzae isolates, including both typeable and nontypeable strains. HMW1/HMW2-like proteins are expressed by the majority of nontypeable clinical isolates and are absent from typeable strains. Hia is expressed by nearly all nontypeable strains that lack HMW adhesins, and Hsf is a homolog of Hia that is universally present among typeable H. influenzae strains, including both type b and non-type b strains. Hap is an example of a conventional autotransporter, Hia/Hsf represent variant autotransporters, and HMW1/HMW2 belong to the TPS pathway. In considering the structural determinants of Hap secretion, it is informative to examine the structural elements that are common to Hap and other conventional autotransporters. Given the similarity between the HMW1 and HMW2 systems, in the chapter, the authors focus primarily on HMW1. The sequence homology, similar functions, shared secretion pathway, and shared immunoreactive epitopes between the HMW proteins and filamentous hemagglutinin (FHA) may indicate that these adhesins have similar structures. The chapter suggests that the HMW1 and HMW2 adhesins adopt β-helical structures. As highlighted in this chapter, recent crystal structures have provided important insights into the mechanisms by which Hap, Hia/Hsf, HMW1/HMW2, and other type V secretion pathway proteins are presented on the bacterial surface and are able to interact with host cells.