Table 1 Natural anti-biofilm agents and their molecular mechanisms in anti-biofilm effects

N-(Heptylsulfanylacetyl)-l-homoserine lactone (Garlic extract)

Transcriptional regulators LuxR and LasR

P. aeruginosa

Decreased elaboration of virulence factors and reduced production of QS signals

[23,24,25]

Ethyl acetate fraction of Cocculus trilobus

Sortase

Gram positives bacteria

Exerted anti-adhesin effects at the adhesion stage of biofilm formation

[26]

Polyphenols (Cranberry)

Glucan-binding proteins, enzymes involved in biofilm formation

Cariogenic and periodontopathogenic bacteria

Affected the destruction of the extracellular matrix, carbohydrate production, bacterial hydrophobicity, proteolytic activities and coaggregation which involved in biofilm formation

[27,28,29,30,31]

Patriniae

Biofilm-associated genes

P. aeruginosa

Inhibited biofilm formation and reduced exopolysaccharide production

[32]

Ginkgolic acids

Curli genes and prophage genes

E. coli O157:H7

Inhibited biofilm formation on the surfaces of glass, polystyrene and nylon membranes

[33, 34]

Cinnamaldehyde

DNA-binding ability of LuxR

E. coli and Vibrio spp.

Affected biofilm formation and structure, the swimming motility, stress response and virulence

[35, 36]

Phloretin

Toxin genes (hlyE and stx(2)), autoinducer-2 importer genes (lsrACDBF), curli genes (csgA and csgB), and prophage genes in E. coli O157:H7

E. coli O157:H7

Reduced biofilm formation and fimbria production

[37]

Phloretin

Efflux protein genes

S. aureus RN4220 and SA1199B

Anti-biofilm formation at low concentration (1–256 μg/ml)

[38]

Isolimonic acid

luxO and AI-3/epinephrine activated cell–cell signaling pathway

Vibrio harveyi

Interfered with cell–cell signaling and biofilm formation

[39, 40]

Hordenine

QS-related genes

P. aeruginosa

Blocked QS-controlled phenotypes like biofilm formation and reduced virulence factors

[41, 42]

Quercetin

SrtA

Streptococcus pneumoniae

Blocked function of SrtA, affect sialic acid production and impair biofilm formation

[49]

Quercetin

LasI, LasR, RhlI and RhlR

P. aeruginosa

Inhibited biofilm formation and production of virulence factors

[44,45,46,47,48]

Quercetin

pH

S. mutans

Disrupted the pH in biofilm

[50]

Quercetin

Glycolytic, protein translation-elongation and protein folding pathways

Enterococcus faecalis

Blocked glycolytic, protein translation-elongation and protein folding pathways

[51]

Methanolic fraction of Zingiber officinale

The virulence genes, F-ATPase activity, surface protein antigen SpaP

S. mutans

Inhibition of surface protein antigen SpaP and inhibitory effect on cell-surface hydrophobicity index of S. mutans

[53]

Ethanolic extract of P. betle leaf (PbLE)

Pyocyanin

P. aeruginosa strain PAO1

Inhibition of Pyocyanin production and reduction of swarming, swimming, and twitching ability of the bacteria by PbLE extract

[54]

Bergenia crassifolia (L.) leaf extract

Gtfs, EPSs

S. mutans

Decreased the adherence property of S. mutans through inhibiting Gtfs to synthesize EPSs

[55]

Ethanol extract from Rhodomyrtus tomentosa

Not investigated

S. aureus, Staphylococcus epidermidis

Inhibited staphylococcal biofilm formation and killed mature biofilm

[56]

Extract of Hymenocallis littoralis leaves

Adhesin proteins, SrtA and Als3

S. aureus NCIM 2654 and C. albicans NCIM 3466

Antimicrobial, anti-biofilm formation and antioxidant activities

[57]

Polyphenolic extract (Epigallocatechin-3-gallate) from Camellia sinesis

Not investigated

Stenotrophomonas maltophilia (sm) isolated from cystic fibrosis (CF)

Reduced bacterial cell viability in biofilm in vitro and significantly reduced Sm bacterial counts in an acute infection model with wild type and CF mice

[58]

Polyphenolic extract from Rosa rugose tea

QS-controlled violacein factors

Chromobacterium violaceum 026, E. coli K-12 and P. aeruginosa PAO1

Inhibited swarming motility and biofilm formation

[59]

Erianin

SrtA

S. aureus

Downregulated SrtA, thereby inhibited cell adhesion

[60]

Isovitexin

SpA

USA300

Reduced SpA and inhibited biofilm formation

[61]

Parthenolide

LasI, RhlI, LasR, RhlR, and extracellular polymeric substance

P. aeruginosa PAO1

Inhibited QS related genes expression including LasI/LasR and RhlI/RhlR and downregulated extracellular polymeric substance

[62]

Extract of Chamaemelum nobile flowers

Not investigated

P. aeruginosa PAO1 and strains isolated from patients

Inhibition of bacteria swarming and biofilm formation

[76]

Wheat-bran

AHL

S. aureus

Inhibition of QS and biofilm formation through downregulating AHLs level

[77]