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

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.