The roles of tetraspanins in bacterial infections

Tetraspanins, a wide family composed of 33 transmembrane proteins, are associated with different types of proteins through which they arbitrate important cellular processes such as fusion, adhesion, invasion, tissue differentiation and immunological responses. Tetraspanins share a comparable structural design, which consists of four hydrophobic transmembrane domains with cytoplasmic and extracellular loops. They cooperate with different proteins, including other tetraspanins, receptors or signalling proteins to compose functional complexes at the cell surface, designated tetraspanin-enriched microdomains (TEM). Increasing evidences establish that tetraspanins are exploited by numerous intracellular pathogens as a doorway for entering and replicating within human cells. Although previous surveys focused mainly on viruses and parasites, it is now becoming clear that bacteria interact with tetraspanins, using TEM as a "gateway" to infection. In this review, we examine the biological functions of tetraspanins that are relevant to bacterial infective procedures and consider the available data that reveal how different bacteria benefit from host cell tetraspanins in infection and in the pathogenesis of diseases. We will also emphasise the stimulating potentials of targeting tetraspanins for preventing bacterial infectious diseases, using specific neutralising antibodies or anti-adhesion peptide-based therapies. Such innovative therapeutic opportunities may deliver alternatives for fighting difficult-to-manage and drug-resistant bacterial pathogens.