Mechanism of bacterial adhesion and embedment in a DNA biofilm matrix: Evidence that binding of outer membrane lipopolysaccharide (LPS) to HU is key

In biofilms, bacteria are embedded within a matrix of extracellular DNA (e-DNA). Since bacterial cells and e-DNA are both negatively-charged, a positively-charged substance must act like a ‘glue’ to allow bacteria to be embedded within the DNA matrix. Here we show that HU (a highly-abundant, histone-like, nucleoid-associated, DNA-binding protein) facilitates bacterium-bacterium and bacterium-DNA interactions by binding to lipopolysaccharide (LPS), a bacterial outer membrane component. We demonstrate that LPS binds to both the canonical and non-canonical DNA-binding sites on HU. We propose that the hexose sugar-terminal phosphate moieties present in the lipid A head-group of LPS bind to the same lysine/arginine residues that are involved in binding of the pentose sugar-phosphate groups in DNA. Alternate binding of LPS and DNA by HU’s DNA-binding sites could allow HU to bind to bacterial cells surfaces and thus elicit bacterium-bacterium and bacterium-DNA interactions in biofilms.