Table 2.
Summary of the role of two-component systems and other regulatory genes involved in the virulence genes expression in Staphylococcus aureus [77,78,79,80,81,82,83].
| Regulators | Functions |
|---|---|
| AgrCA | Cell-to-cell communication system, where the bacteria communicate with self-produced autoinducing peptide Essential for biofilm disassembly and initial attachment Agr regulation represses adhesins and stimulates phenol-soluble modulins and proteases |
| AirSR/YhcSR | Involved in cellular homeostasis and energy production Important for aerobic and anaerobic growth Positively regulates the expression of the sspABC operon |
| ArlRS | Positive regulator of MgrA and Spx Regulates many cellular processes, including cell wall-anchored adhesins, virulence factors, polysaccharides, and capsular synthesis genes |
| BceRS | Positive regulator of bceAB and vraDE genes Confers resistance towards bacteriocins by transporting bacteriocins outside the cytoplasm through BceAB and VraDE proteins |
| BraSR | Confers resistance towards nisin A and nukacin ISK-1 Exhibits significant regulatory effects on the symbiosis of S. aureus and the type I bacteriocin strain |
| CodY | Strain-dependent regulation of PIA Positive regulator of biofilm formation through the induction of ica operon Cytoplasmic regulator for metabolic response Positive regulator of virulence factor protease |
| GraRS/ApsRS | Belongs to the intramembrane-sensing histidine kinase (IM-HK) familyPositively regulates expression of the dlt operon Essential in evading host defense mechanisms such as neutrophil killing and cationic AMPs |
| HptRS | Hexose phosphate transporter Primarily involved with hptA (initiates autophosphorylation of hptS based on the phosphate concentration), uhpT (downstream regulatory protein transports phosphate/fosfomycin into the bacterial cell to maintain physiological metabolism) Mutation reduces the uptake of fosfomycin (structure similar to phosphoenolpyruvate) and increases the bacterial resistance |
| HssRS | Heme sensor system responding to heme exposure Positive regulator of the efflux pump HrtAB (heme-regulated transporter), which plays a role in maintaining intracellular heme homeostasis Found to have a role in regulating virulence and modulating host immune response |
| KdpDE | Involved in sensing potassium (K+) limitation or salt stress It plays a role in the expression of genes involved in capsule biosynthesis, amino acid and central metabolism |
| LytRS | Regulates cell lysis and induces the expression of irgAB Plays a predominant role in eDNA-mediated biofilm formation |
| MgrA | SarA family cytoplasmic regulator and prime effector of the ArlRS system Repression of adhesins and negative regulator of biofilm formation |
| NreCB | Involved in oxygen sensing; converts nitrate and nitrite as final oxygen acceptors Regulates the gene clusters involved in nitrate (narGHJI) and nitrite reduction (nirRBD) Expression is controlled by NreA, which inhibits NreB autophosphorylation |
| NsaRS | Belongs to the IM-HK family Important in conferring resistance towards nisin |
| PhoRP | Involved in response to inorganic phosphate starvation Positive regulator of pstSCAB and nptA, and also modulates the expression of pitA |
| Rot | SarA family cytoplasmic regulator and prime effector of the Agr QS system Positive regulator of biofilm formation through protease repression and adhesin induction |
| SaeRS | Stimulates adhesin and nuclease production and is very much crucial in the biofilm maturation process |
| SarA | Positive regulator of biofilm formation through the induction of ica operon Induces biofilm formation through the repression of protease production |
| SigB | Strain-dependent regulation of PIA Positive regulator of virulence factors protease and nucleaseEssential for initial attachment and biofilm disassembly Cytoplasmic regulator for stress response |
| SrrAB | Global regulator for S. aureus virulence Critical for survival under environmental stress Regulation of genes involved in anaerobic metabolism, nitrous oxide detoxification, cytochrome biosynthesis and assembly, biofilm formation, hydrogen peroxide metabolism, and programmed cell death |
| VraRS | Associated with vancomycin resistance Essential for cell wall synthesis Positive regulator of PBP2, SgtB, and MurZ |
| WalKR/YycGF | Essential for cell wall metabolism and cell viability Positive regulator of AtlA, SsaA, IsaA, and LytM Regulates the expression of host matrix interaction proteins, cytolytic toxins, and proteins involved in host immune evasion |