The role of extracellular DNA in the formation, architecture, stability, and treatment of bacterial biofilms

Abstract

Advances in biotechnology to treat and cure human disease have markedly improved human health and the development of modern societies. However, substantial challenges remain to overcome innate biological factors that thwart the activity and efficacy of pharmaceutical therapeutics. Until recently, the importance of extracellular DNA (eDNA) in biofilms was overlooked. New data reveal its extensive role in biofilm formation, adhesion, and structural integrity. Different approaches to target eDNA as anti-biofilm therapies have been proposed, but eDNA and the corresponding biofilm barriers are still difficult to disrupt. Therefore, more creative approaches to eradicate biofilms are needed. The production of eDNA often originates with the genetic material of bacterial cells through cell lysis.However, genomic DNA and eDNA are not necessarily structurally or compositionally identical. Variations are noteworthy because they dictate important interactions within the biofilm. Interactions between eDNA and biofilm components may as well be exploited as alternative anti-biofilm strategies. In this review, we discuss recent developments in eDNA research, emphasizing potential ways to disrupt biofilms. This review also highlights proteins, exopolysaccharides, and other molecules interacting with eDNA that can serve as anti-biofilm therapeutic targets.Overall, the array of diverse interactions with eDNA is important in biofilm structure, architecture, and stability. K E Y W O R D Santi-biofilm therapies, biofilms, eDNA, eDNA therapy, eDNA-interactions | BACKGROUNDA global health crisis is growing due to antibiotic resistance. Antibiotics were first prescribed to treat severe infections after Alexander Fleming discovered penicillin in the 1940's. Over time, various classes of antibiotics that target different bacterial machineries were introduced to the market. However, in recent years, the rate of discovery of new antibiotic classes has stagnated whereas the rate of antibiotic consumption has continued to increase (Silver, 2011). As a result, antibiotic resistance can emerge as bacteria respond to therapeutic treatments. The Centers for Disease Control and Prevention reports that at least 2.8 million people get infected and at least 35,000 die because of antibiotic resistant bacteria in the United States annually (CDC, 2019). In Europe, an estimated number of 25,000 deaths are associated to antibiotic resistant bacteria ("Annual report of the European Medicines Agency," 2010). Greater than 30,000 deaths per year are reported in countries like Thailand as well as increasing variants of antibiotic resistant bacteria emerging in South America, the Middle East, and Asia (Howell, 2013). In addition to these statistics, neonatal sepsis attributed to antibiotic resistance are increasing in Tanzania and Mozambique, and approximately 58,000 neonatal sepsis deaths related to antibiotic resistance are reported in India (Hellen et al., 2015

DNase inhibits early biofilm formation in Pseudomonas aeruginosa- or Staphylococcus aureus-induced empyema models

“…This finding suggests that the mode of action of intrapleural DNase therapy may be to inhibit early biofilm formation in pleural empyema. eDNA is known to be important for biofilm stability, and DNase treatment can remove eDNA from biofilms, particularly during bacterial attachment and the initial stages of biofilm formation (Panlilio and Rice, 2021). Cleavage of eDNA by DNase can promote the penetration of antibiotic molecules and decrease biofilm biomass (Liu et al, 2020).…”

Biofilm formation as an extra gear for Apilactobacillus kunkeei to counter the threat of agrochemicals in honeybee crop

“…It could explain the strong contrasting action towards the biofilm growth, since both EPS and proteins play an essential role in biofilm expansion other then as protective agents (Karygianni et al ., 2020). Also, extracellular DNA aids in bacterial attachment and aggregation, but it is critical especially in the early stages of biofilm formation (Panlilio and Rice, 2021).…”

Recognition of extracellular DNA by type IV pili promotes biofilm formation by Clostridioides difficile

“…The formation of C. difficile biofilms in vitro is typically studied in monoculture, but in vivo, interactions with other bacterial species, either pathogens or commensal members of the gut microbiome, may play an important role (14,15), either cooperatively or competitively. Bacterial biofilms are composed not only of bacterial cells, but an extensive extracellular matrix composed of polysaccharides, extracellular DNA and polypeptides (16)(17)(18)(19), either as monomers (20) or as surface assemblies (21,22). Previously, our group and others have reported a defect in in vitro biofilm formation for mutations in the Type IV pilus (T4P) system in C. difficile (7)(8)(9).…”

“…Bacterial biofilms are composed not only of bacterial cells but an extensive extracellular matrix composed of polysaccharides, extracellular DNA, and polypeptides ( 16 , 17 , 18 , 19 ), either as monomers ( 20 ) or as surface assemblies ( 21 , 22 ). Previously, our group and others have reported a defect in in vitro biofilm formation for mutations in the type IV pilus (T4P) system in C. difficile ( 7 , 8 , 9 ).…”