TABLE 2.

Mechanisms of known biofilm signals and regulators in A. baumannii, Klebsiella sp., and Enterobacter sp.

Microorganism	Biofilm signals and regulators	Mechanisms	References
Acinetobacter sp.	– Csu assembly system composed from pilin subunits CsuA/B, CsuA, CsuB, and CsuE and transport proteins CsuC and CsuD – OmpA (Outer membrane protein A) – Biofilm-associated protein (Bap) – β-lactamase blaPER-1 – pil operon, codifying for type IV pili, pap operon, and prpABCD operon codifying also for pili – Poly-β-(1,6)-N-acetylglucosamine (PNAG)	– biofilm formation, adherence to the inert surfaces in many biofilm forming Acinetobacter baumannii strains, – biofilm formation, adherence of the strains to inert surfaces and host cells, – adherence to bronchial cells and for biofilm structure integrity, – increases adherence to the substratum, – involved in adherence and biofilm formation, – extracellular polysaccharide; function as intercellular adhesin within the biofilm.	Brossard and Campagnari, 2012; Yang et al., 2019; Colquhoun and Rather, 2020
	– AbaI/R QS system – BfmRS two component system – AdeRS, GacSA two component systems – cyclic di-GMP	– regulate biofilm formation, – biofilm master regulator, involved in regulation of csu operon and genes important for virulence and desiccation tolerance, – regulates pili synthesis, motility, biofilm formation, – regulate signaling in biofilms.	Ahmad et al., 2020; Colquhoun and Rather, 2020
Klebsiella sp.	– type 3 fimbriae (subunit MrkA, a chaperone-usher system MrkBC, the fimbrial tip adhesin MrkD, and MrkF) – CPS (capsular polysaccharides) – second messenger cyclic-di-GMP (c-di-GMP) – MrkH and MrkI transcriptional activators (encoded by mrkHIJ gene clusters) – MrkI – histone-like nucleoid-structuring protein (H-NS), CRP – ferric uptake regulator (Fur) – RcsAB (a two-component regulator of capsule synthesis) – IscR (iron-sulfur cluster regulator) – AI-2 interspecies QS system	– mediate stable adherence in biofilm, – involved in cell-to-cell communication and biofilm architecture, – biofilm regulation by control of type 3 fimbrial production (decrease concentration of c-di-GMP decreased the expression of the mrkABCDF preventing the synthesis of the type 3 fimbriae), – control c-di-GMP dependent phenotypes, – act as functional c-di-GMP phosphodiesterase and conduct to hydrolysis of c-di-GMP repressing type 3 fimbriae expression and biofilm formation, – control of type 3 fimbriae expression, – type 3 fimbriae expression, capsula and biofilm formation in K. pneumoniae, – regulate transcription of galF gene (controlling the biosynthesis of capsular polysaccharide) by binding to the galF promoter DNA, – modulate the iron-acquisition system and attachment, – regulate biofilm formation and LPS synthesis in K. pneumoniae biofilm by increase in the expression of two LPS-synthesis – related genes, wbbM and wzm.	Johnson et al., 2011; Piperaki et al., 2017,De Araujo et al., 2010; Johnson et al., 2011; Lin et al., 2017; Peng et al., 2018; Zhang et al., 2021
Enterobacter sp.	– ‘curli fimbriae’ – the second type VI secretion system (T6SS-2) – mRNA expression level of csgA and csgD genes (curli biogenesis genes).	– protein extracellular fibers involved in host cell adhesion and invasion, control the formation and architecture of E. cloacae biofilms, modulate adherence to abiotic and biotic surfaces, – regulate biofilm formation in Enterobacter sp.	Mezzatesta et al., 2012; Soria-Bustos et al., 2020,Soares et al., 2016