The Acinetobacter baumannii Autotransporter Adhesin Ata Recognizes Host Glycans as High-Affinity Receptors

Abstract

Acinetobacter baumannii is a significant opportunistic pathogen responsible for infections of the lung, blood, skin, urinary tract, and soft tissues, with some strains exhibiting almost complete resistance to commonly used antibiotics. This multidrug resistance, together with a dearth of new antibiotic development, mean novel methods of treatment and prevention are urgently needed. Although many A. baumannii factors required to colonize the host have been identified, little is known about the specific host molecules recognized by these factors. A. baumannii produces a trimeric autotransporter adhesin known as Ata that has been previously demonstrated to bind components of the host cell's extracellular matrix, which are often heavily glycosylated. We hypothesized that Ata would exhibit lectin activity which would play a role in adherence to the host cell surface. Our biophysical analysis using glycan arrays and surface plasmon resonance demonstrated that Ata binds galactose, N-acetylglucosamine, and galactose (β1−3/4) N-acetylglucosamine with high-affinity. These structures are present on many of the proteins which were previously reported to be bound by Ata. We also demonstrated that the recognition of human plasma fibronectin by Ata requires this ability to bind glycans, as the interaction between Ata and fibronectin does not occur when fibronectin is deglycosylated. This strongly suggests a key role for Ata lectin activity during host adherence. This information will assist in directing the development of new and effective treatments to block host interactions using glycans and/or novel compounds in multidrug resistant A. baumannii infections.

InvL, an invasin-like adhesin, is a type II secretion system substrate required for Acinetobacter baumannii uropathogenesis

“…ECM components bound by Type IV pili and Bap are not known. However, Ata has been shown to bind with high affinity to collagen (types I, III, IV, and V), laminin, and glycosylated fibronectin, and FhaBC reportedly binds to fibronectin (85, 88, 89, 92). While the collagen-binding role of InvL may be redundant with that of Ata, InvL is the first published Acinetobacter adhesin to bind directly to α5β1 integrin or fibrinogen.…”

“…Our characterization of InvL adds to the growing list of known Acinetobacter adhesins that facilitate binding to epithelial cells, which includes Type IV pili, the Ata autotransporter, the FhaB/FhaC two-partner secretion system, and biofilm-associated protein (Bap) (83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93). ECM components bound by Type IV pili and Bap are not known.…”

How bacteria utilize sialic acid during interactions with the host: snip, snatch, dispatch, match and attach

“…For example, P. aeruginosa pili and flagellum interact with GM1 and GM2 gangliosides containing α2,3linked Neu5Ac residues [109]. In an interesting example of sialylation not increasing adherence to the underlying glycans, the Ata adhesin of the multi-drug-resistant pathogen A. baumannii interacts with high-affinity to N-Acetylactosamine, which consists of a galactose and GlcNAc joined by a β1-4 linkage [110]. Sialylation of the GlcNAc with Neu5Ac to form sialyllactosamine did not change the affinity of the interaction [110].…”

“…In an interesting example of sialylation not increasing adherence to the underlying glycans, the Ata adhesin of the multi-drug-resistant pathogen A. baumannii interacts with high-affinity to N-Acetylactosamine, which consists of a galactose and GlcNAc joined by a β1-4 linkage [110]. Sialylation of the GlcNAc with Neu5Ac to form sialyllactosamine did not change the affinity of the interaction [110]. This suggests that Neu5Ac may not be 'seen' by Ata, with the underlying structure of N-acetylactosamine, or the individual components of this structure, more important to binding, and that not all human pathogens have an affinity for sialic acids.…”

A Short Peptide of Autotransporter Ata Is a Promising Protective Antigen for Vaccination Against Acinetobacter baumannii

“…Acinetobacter trimeric autotransporter (Ata) of A. baumannii ATCC 17978, belongs to the trimeric autotransporter adhesin superfamily and is secreted through a type V secretion system. Trimeric autotransporter adhesins act as key virulence factors in many Gram-negative bacteria; participate in adhesion, biofilm formation, immune evasion, angiogenesis, and cell death; and mediate adhesion to extracellular matrix proteins in a murine pneumonia model ( 8 , 22 , 23 ). Ata is a potential vaccine target, and research has shown that antibodies against Ata are highly opsonic against A. baumannii and show low-to-moderate killing activity against four A. baumannii strains ( 22 , 24 ).…”