Table 2.

Studies using dimethyl-sulfoxide (DMSO) as a treatment in in vitro antibiofilm assays: general results and proposed mechanisms of action. ATCC: American Type Culture Collection; EPS: exopolysaccharide; QS: quorum sensing.

Target species	DMSO conc.	DMSO effect on biofilms	Proposed mechanism of action	Ref
Burkholderia cepacia; B. pyrrocinia (clinical isolate); Pseudomonas aeruginosa	10–100%	DMSO dissociated double-stranded segments of cepacian (EPS) molecules leading to dispersion of polymeric chains and formation of a porous biofilm	DMSO induces disruption of polymer chain aggregation in polysaccharides	[102]
Staphylococcus aureus strains 72, 80, 510, ATCC 29213	1/1, 1/3, 1/9 v/v	When directly adding DMSO to a biofilm, a complete disruption of this biofilm was macroscopically observed	Not provided	[96]
P aeruginosa (PAO1), Escherichia coli	2% v/v (10% v/v for model)	DMSO significantly attenuated a range of QS-controlled virulence factors and biofilm formation at a non-inhibitory growth concentration; DMSO did not affect antibiotic MICs up to 2%; DMSO treatment reduced mortality in a murine model of P. aeruginosa wound infection	Reduction of C4-HSL (N-butanoyl-l-homoserine lactone) involved in las and rhl QS systems was the main influence on virulence factors; “[the impact of DMSO] on virulence factors of bacterial pathogens complicates its usage as a solvent in biological and medicinal studies.”	[25]
E. coli UTI89, UTI89csgA, MC4100, MC4100csgA	0.05–4%	At low concentrations (<1%) DMSO had no effect, at high concentrations (2–4%) DMSO (and ethanol, but to a lesser extent) increased cellular agglutination in broth and increased curli expression (adhesion molecule) to enhance biofilm formation	Effects currently not understood at the molecular and atomic level; “DMSO was not being metabolized or transformed by E. coli."	[108]
E. coli (n = 10), Klebsiella pneumoniae (n = 10), and P. aeruginosa (n = 8) isolates	30%	DMSO significantly reduced preformed biofilm biomass and viable colony forming units; more effective than other tested agents (hypochlorous agents, ozone, antimicrobial peptide mimic); different efficacy depending on bacteria species	Not provided	[113]
Pseudomonas fluorescens (H2S)	2% and 5%	“Treatment with DMSO produced different results in separate experiments, causing a slight decrease in biofilm thickness at 2% and at times an increase at 5% (data not shown)"	Not provided	[95]
Shewanella sp. (20 strains from various environmental and clinical sources)	0.55–70 mM	DMSO (35 mM) increased biofilm production up to 3-fold in some isolates, but not in others, under different conditions- addition of nitrates (electron acceptors) resulted in a 3-fold reduction in biofilm formation at the same DMSO concentration	DMSO reduction is variable among certain isolates; respiration-driven biofilm formation may constitute a mechanism of niche colonization by specialized strains; a terminal DMSO reductase is involved in extracellular respiration and uses sulfoxides and N-oxides as substrates	[110]
Staphylococcus epidermidis (ATCC 35984)	0.0039–1%	Biofilm formation stimulated by 12–42% (p < 0.05) with DMSO	Likely strain dependent; recommend use of <1% methanol as solvent as opposed to DMSO	[109]
Corynebacterium pseudotuberculosis (clinical isolate); Salmonella typhimurium ATCC 14028	50, 25, 12.5, 6.25, 3.13, 1.56%	DMSO significantly inhibited C. pseudotuberculosis biofilm formation at all concentrations relative to the control but the effect was similar between concentrations.	DMSO may inhibit functional linkages between glycolytic enzymes (hub proteins)	[103]
C. pseudotuberculosis (clinical isolate); S. typhimurium (ATCC 14028)	50, 25, 12.5, 6.25, 3.13, 1.56%	All DMSO concentrations significantly inhibited C. pseudotuberculosis biofilm but not S. typhimurium and was the more effective than EDTA and EtOH	“Inhibition of bacterial growth by DMSO is known to involve membrane perturbation."	[114]
S. typhimurium (ATCC 14028)	1–32%	DMSO (32%) inhibited pellicle formation, biofilm viability, biofilm biomass and several important components of the EPS matrix; planktonic bacteria were affected differentially by different DMSO concentrations	“Protein interaction network analysis identified several biological pathways to be affected, including glycolysis, PhoP–PhoQ phosphorelay signalling and flagellar biosynthesis; DMSO may inhibit multiple biological pathways to control biofilm formation."	[100]
E. coli ATCC 1299, P. aeruginosa (ATCC 10145), and S. typhimurium (ATCC 14029)	1–32%	Significantly lower EPS protein conc with DMSO alone (32%) and afatanib + DMSO treatments; “planktonic fractions were affected differentially by DMSO” - killing effect at 10% DMSO	“DMSO, but not afatinib, is regarded as an effective antibiofilm agent [at 32%]. Chemical modification of EPS matrix may account for, at least, a part of the mode of action of DMSO.”	[26]