Multitasking functions of bacterial extracellular DNA in biofilms

Abstract

Bacterial biofilms are intricate ecosystems of microbial communities that adhere to various surfaces and are enveloped by an extracellular matrix composed of polymeric substances. Within the context of bacterial biofilms, extracellular DNA (eDNA) originates from cell lysis or is actively secreted, where it exerts a significant influence on the formation, stability, and resistance of biofilms to environmental stressors. The exploration of eDNA within bacterial biofilms holds paramount importance in research, with far-reaching implications for both human health and the environment. An enhanced understanding of the functions of eDNA in biofilm formation and antibiotic resistance could inspire the development of strategies to combat biofilm-related infections and improve the management of antibiotic resistance. This comprehensive review encapsulates the latest discoveries concerning eDNA, encompassing its origins, functions within bacterial biofilms, and significance in bacterial pathogenesis.

Keywords: biofilm; extracellular DNA (eDNA); extracellular polymeric substances (EPSs); horizontal gene transfer (HGT); quorum sensing (QS).

Fig 1

Source of eDNA within biofilms. eDNA release in biofilms occurs through both lysis-dependent and -independent mechanisms. Lysis-dependent mechanisms include programmed bacterial apoptosis, fratricide-induced death, exposure to sublethal doses of antibiotics, and the action of bacteriophages. Lysis-independent mechanisms include the active secretion of DNA by the type IV secretion system (T4SS), the production of membrane vesicles (MVs) filled with eDNA, and the formation of neutrophil extracellular traps (NETs) by polymorphonuclear leukocytes/neutrophils.

Fig 2

Dynamic niche of bacterial biofilms and NETs. (A) Biofilms are complex communities of bacteria embedded in a self-produced extracellular matrix (ECM) that provides structural support, protection from environmental insults, and a means of communication. EPSs, a major component of the ECM, interact with eDNA to form a mesh-like structure that enhances biofilm stability and resistance to antibiotic treatment. QS signals, which are molecules that bacteria use to communicate with each other, trigger the release of eDNA from biofilm-associated bacteria. Along with other matrix proteins, the biofilm matrix protein DNABII helps to stabilize the conformation of eDNA and facilitates processes such as horizontal gene transfer (HGT). (B) Neutrophils, the predominant white blood cells in the immune system, employ a powerful weapon against invading microbes: NETs. These intricate mesh-like structures, composed of eDNA and antimicrobial proteins, serve as sticky nets to capture and eliminate individual bacteria. In the context of biofilms, which are densely packed communities of bacteria that adhere to surfaces, NETs play a crucial role in preventing biofilm growth and spread. However, the effectiveness of NETs hinges on the structural integrity of the DNA backbone. In its native B-form, eDNA is robust and resilient, enabling NETs to effectively capture and immobilize bacteria. However, certain proteins, such as DNABII, can induce a structural transition from the B-form to the Z-form DNA. This conformational change weakens the NET structure, compromising its ability to trap and eliminate bacteria.