Bacterial Biofilms Utilize an Underlying Extracellular DNA Matrix Structure That Can Be Targeted for Biofilm Resolution

Abstract

Bacterial biofilms contribute significantly to the antibiotic resistance, pathogenesis, chronicity and recurrence of bacterial infections. Critical to the stability and survival of extant biofilms is the extracellular DNA (eDNA)-dependent matrix which shields the resident bacteria from hostile environments, allows a sessile metabolic state, but also encourages productive interactions with biofilm-inclusive bacteria. Given the importance of the eDNA, approaches to this area of research have been to target not just the eDNA, but also the additional constituent structural components which appear to be widespread. Chief among these is a ubiquitous two-member family of bacterial nucleoid associated proteins (the DNABII proteins) responsible for providing structural integrity to the eDNA and thereby the biofilm. Moreover, this resultant novel eDNA-rich secondary structure can also be targeted for disruption. Here, we provide an overview of both what is known about the eDNA-dependent matrix, as well as the resultant means that have resulted in biofilm resolution. Results obtained to date have been highly supportive of continued development of DNABII-targeted approaches, which is encouraging given the great global need for improved methods to medically manage, or ideally prevent biofilm-dependent infections, which remains a highly prevalent burden worldwide.

Keywords: NET; PMN; Z-DNA; biofilm; chinchilla; disruption; humanized monoclonal antibody; nucleoid associated proteins; tip-chimer peptide.

Figure 1

Localization of a DNABII protein at vertices of bent eDNA within an in situ biofilm. (A) Immunofluorescent image of a biofilm formed in the middle ear of the chinchilla (21 days after challenge with non-typeable Haemophilus influenzae). Fine, widely spaced dsDNA strands are labeled with DAPI and appear blue in this image, whereas non-typeable H. influenzae are labeled with FITC-conjugated antiserum directed at a surface-exposed protein and appear green. Marker bar = 5 µm. (B) DNABII family members have a stronger preference for binding to bent DNA—a generalized scheme. (C) Immunohistochemical labeling of IHF within an NTHI biofilm formed in vivo. The strong labeling of each vertex where individual strands of DNA cross (arrows) must be noted. FITC, fluorescein isothiocyanate; IHF, integration host factor; NTHI, non-typeable Haemophilus influenzae. Reprinted from Ref. [9].