The roles of tetraspanins in bacterial infections

Abstract

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.

Antimicrobial Effects of Tetraspanins: A New Turnabout in Treatment of Microorganisms

“…Tetraspanins can interact with different types of proteins such as adhesion molecules, immunoglobulin, signaling receptors, intracellular signaling molecules and immune signaling molecules ( 3 , 6 ). Tetraspanins also can interact with lipids namely membrane gangliosides and cholesterol ( 3 , 7 ). The web of tetraspanins allows it to form larger downstream complexes.…”

“…They are known to be the ‘gateway’ for infections through their TEM-dependent complexes at the EC2 region ( 5 , 11 ). Tetraspanins are utilised directly or indirectly by the pathogens to manipulate the normal cellular processes for pathogens binding, intracellular trafficking, replication, and infection development within the human cells ( 7 ). Tetraspanins are well documented to be associated with the hepatitis C virus and human immunodeficiency virus (HIV) for viral entry into the host cells ( 5 ).…”

“…Previous studies have reported that tetraspanin-mediated adhesion is the initial step for the bacterial in invading the host cells and breaching the host cells barrier. Uroplakin 1a (TSPAN21) and Uroplakin 1b (TSPAN20) have been found to attach to the type 1 fimbriae, Fim H adhesin of uropathogenic Escherichia coli that invaded the bladder epithelial cells leading to urinary tract infections in humans ( 5 , 7 ). The involvement of tetraspanins in viral infections has been reviewed since 2005 by Martin and the team ( 12 ).…”

Mycobacterium abscessus alkyl hydroperoxide reductase C promotes cell invasion by binding to tetraspanin CD81

“…Tetraspanins belong to a superfamily of glycoproteins, which span the membrane four times and possess a small (SEL) and a large extracellular loop (LEL). 22 These proteins display a wide panel of cellular functions (adhesion, motility, and fusion) and are related to infection by a variety of human pathogens, including viruses, parasites and bacteria. 22 Humans possess 33 tetraspanins, with most cells expressing simultaneously multiple members of this family of proteins.…”

CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway

“…Partner proteins can include integrins, HSPGs and immunoglobulin superfamily members (Umeda et al, 2020), many of which are important in host cell adherence and entry of microbial pathogens. The tetraspanins have been implicated in a number of different viral and bacterial infections (Florin and Lang, 2018; Karam et al, 2020). We have previously demonstrated that tetraspanin blockade, using antibodies or recombinant EC2 domains, can significantly reduce Gram-negative and Gram-positive bacterial adherence to epithelial cells (Green et al, 2011).…”