Table 1 Genes involved in biofilm development in S. aureus categorized by every developmental stage

srtA (RN4220, OS2 and Newman strains)

Sortase A

Extracellular transpeptidases responsible for anchoring the cell-wall-anchored proteins in S. aureus and Gram-positive bacteria.

[25]

fnBP A/B (8325 strain)

Fibronectin-binding protein A and B

Members of the MSCRAMMs group responsible for binding to components of the extracellular matrix such as fibrinogen, fibronectin, and elastin.

[26]

Clf A/B (Newman strain)

Clumping-factor A and B

Glycoprotein; members of the MSCRAMMs group responsible for clumping bacterial cells prior to recognizing and binding to host matrix fibrinogen.

[27]

spA (ISP479r strain)

Protein A

A cell wall-anchored protein recognizing platelet-secreted immunoglobulin G

[28]

EbpS (strain 12,598 Cowan)

Elastin-binding protein

A cell-wall protein responsible for binding to the N-terminal region of the elastin present in host extracellular matrix.

[29]

Pls (1061 strain)

Plasmin-sensitive protein

A virulence factor encoded by a gene carried on the staphylococcal cassette chromosome (SCC) mec type I in MRSA. It stimulates biofilm formation.

[30, 31]

SasG (8325–4 and Newman strains)

S. aureus surface protein G

Surface protein that allows attachment to squamous and desquamated epithelial cells, promotes colonization and stimulates biofilm formation.

[32]

IsdA (8325–4 strain)

Iron-regulated surface protein A

Surface protein; part of the NEAT protein family, has a role in binding to fibrinogen, fibronectin, and loricrin.

[33]

Bbp (E514 and O24 strains)

bone sialoprotein-binding protein

Part of the MSCRAMMs; interacts with bone sialoprotein which is a major component of dentine extracellular matrix (ECM) and bones. It plays a significant role in the colonization of bone tissues.

[34]

dltABCD operon (Sa113 wild-type strain)

D-alanylation proteins

Encodes proteins that act synergistically to mediate the D-alanylation of the teichoic acids; wall-teichoic proteins and lipoteichoic acids anchored in the cell wall.

[35]

AltA (8325–4 strain)

Peptidoglycan hydrolase

An enzyme that has been shown to promote binding to hydrophilic and hydrophobic polystyrene surfaces.

[36]

icaABCD operon (SA113 strain)

polysaccharide intracellular adhesin (PIA/PNAG)

Polymeric carbohydrates form complex networks with each other and are anchored to cell surfaces.

[37]

icaR (RN4220 strain)

intercellular adhesin locus regulator

Locus responsible for downregulating the expression of the icaABCD operon.

[38]

SasG (8325–4 and Newman strains)

S. aureus surface protein G

Surface protein involved in the protein-mediated ica-independent mechanism of accumulation and cell-to-cell attachment.

[32]

AltA (8325–4 strain)

Peptidoglycan hydrolase

AtlA-mediated lysis of the bacterial cells is crucial for the development of the biofilm.

[36]

cidA (UAMS-1)

Putative holin protein

The product of this gene mediates cell lysis during biofilm development.

[39]

Nuc (USA300)

Degradative nucleases

These nucleases play a role in early dispersal of biofilm cells through degrading the eDNA present in the biofilm matrix.

[40]

SaeS (ISP479 and Newman strain)

Sensor histidine kinase

This kinase is responsible for phosphorylation-mediated activation of the SaeR gene upon recognition of environmental signals.

[41]

SaeR (ISP479 and Newman strain)

Response regulator

Upon being activated by the sensor histidine kinase, it induces transcription of around 20 virulence genes

[41]

lrgAB (8325–4 strain)

Putative antiholin

Responsible for inhibiting cell death/lysis, typically those initiated by the cidABC operon.

[42]

cidA (UAMS-1)

Putative holin protein

The product of this gene mediates cell lysis and plays a role in biofilm maturation along with the products of the lrgAB operon.

[39]

Aur (USA300 strain)

Zinc-dependent metalloprotease aureolysin

This protein is crucial for pathogenesis as it targets the components of the complement system inside the infected host. It also targets ClfB and Bap.

[43]

SspB (RN4220 strain)

Cysteine protease

Protease involved in the degradation of collagen.

[44]

SspA (RN4220 strain)

Serine protease

Protease involved in the degradation of FnBP and Bap.

[44]

agrA (RN4220 strain)

AgrA response regulator

AgrA is for controlling the genetic adaptation in response to this signal.

[23]

agrC (RN4220 strain)

Transmembrane signal receptor

AgrC is a histidine kinase responsible for the detection of environmental signals.

agrB (RN4220 strain)

AgrB secretory protein

ArgB is responsible for post-translational modification of AgrD and its secretion into the biofilm milieu.

agrD (RN4220 strain)

AgrD precursor protein

This precursor protein is processed by the AgrB protein to give a mature autoinducing octapeptide.

ccpA (SA113)

Catabolite control protein A

CcpA is responsible for regulating gene expression in response to different sugars used as carbon sources.

[45]

Fur (SH1000 and Newman strains)

Ferric uptake regulator

Controls iron concentrations inside bacterial cells and is involved in a complex regulatory network with both Agr and Sae systems

[46]