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Abstract Quorum sensing refers to the phenomenon that bacteria sense signal molecules in the environment and regulate a series of genes. At present， the known quorum sensing systems in Staphylococcus aureus are the Agr system and the LuxS/AI-2 system. They will be activated when the bacterial concentration is equal to or greater than 107/ml， and by regulating the corresponding genes， bacteria can indirectly or directly regulate the production and degradation of biofilms， the secretion of bacterial toxins and the growth of bacteria. In this paper， we summarized the research progress of quorum sensing in S. aureus by consulting relevant literatures at home and abroad on quorum sensing in S. aureus， so as to find a new direction for the future research on S. aureus.
Key words Quorum sensing; Staphylococcus aureus; Biofilm; Pathogenicity
Staphylococcus aureus （SA） is a common pathogen causing community- and hospital-acquired infections. It is the main cause of human blood infections and can infect various organs to cause infective endocarditis， suppurative arthritis， and osteomyelitis[1]. SA is also very good at evading the hosts immune system， and constantly develops resistance to antibiotics[2]， which poses a great obstacle to treatment.
The phenomenon of bacteria regulating a series of genes through the sensing of signaling molecules in the environment is called the quorum sensing （QS）， also known as self-induction[3]. Instead of language， bacteria use certain secondary metabolites secreted by themselves as signal molecules. When the bacteria reach a certain threshold concentration， the bacteria generate some gene expression by recognizing these signal molecules， resulting in a series of physiological changes[4-5].
Current experiments have shown that SAs QS system is closely related to SAs toxicity and drug resistance[6-7]. Therefore， interfering with SAs QS system to treat SA infection has become an emerging research hotspot[8]. This paper reviewed the research progress of SAs QS system in recent years.
SAs QS Regulation Network
For SA， at least two QS systems have been currently found， which are divided into the agr systems with autoinducing peptides （AIPs） as signal molecules[9] and the LuxS/AI-2 system with furanosyl borate diester （AI-2） as s signal molecule according to the types of signal molecules[10].
The Agr system is a known QS system in the genus Staphylococcus， which is closely related to the synthesis of SAs toxic factors and cell surface adhesion[11]. The agr locus is 3.5 kb in size and consists of two different transcription units， RNA II and RNA III， which are activated by P2 and P3 promoters， respectively[12]. The RNA II locus contains four genes， agrB， agrD， agrC and agrA. agrD is responsible for encoding extracellular pre-peptides AIPs that can be used as QS signal molecules of agr; the gene product of agrB is a transmembrane endopeptidase， used to introduce lactone modification， C-terminal cleavage and outflow of AIPs; and the agrC and agrA genes encode a two-component signal transduction system， including a histidine kinase sensor AgrC， a transmembrane protein that can bind and phosphorylate AIPs and its associated response regulator AgrA[13]. After phosphorylation activation of AgrC， AgrA binds the P2 promoter region on RNA II and the P3 promoter region on RNA III[14]， and further activates RNA III， which is then translated to produce δ toxin encoded by hld[15]. The LuxS/AI-2 system is a QS system with furanosyl borate diester （AI-2） as a signal molecule. It was first discovered from Vibrio harveyi[16]， and later found to be widespread in most bacteria. The QS system is presumed to be a common language among strains[17]. AI-2 is a by-product of the bacterial methyl cycle. In the methyl cycle， s-adenosylmethionine （SAM） is converted to S-adenosylhomocysteine （SAH）， which is hydrolyzed by 5′-methylthioadenosine/S-adenosylhomocysteinase （Pfs） into S-ribose homocysteine （SRH） and adenine， and then the AI-2 anabolic enzyme LuxS catalyzes SRH into the precursor compound of AI-2， 4，5-dihydroxy-2，3-pentanedione， i.e.， DPD， which is unstable itself， and is further converted into AI-2[18]. AI-2 is closely related to various pathogenicity of SA， such as biofilm formation， sensitivity to antibiotics， and toxicity[19-20].
The Effect of SAs QS System on SA Biofilm
The concept of bacterial biofilm was first proposed by Costerton et al.[21] in 1978. After a lot of research and summary， the academic community generally believes that a bacterial biofilm is a polysaccharide complex secreted by bacteria in order to adapt to the environment， which attaches to the surface of the contact object， and protects the bacteria in the film from antibacterial drugs， while secreting antibiotic inactivating enzymes， which greatly reduce the effects of antibacterial drugs[22]. The biofilm formation process is mainly divided into several steps： （1） bacteria adhere to the surface of non-living things or host matrix proteins， and then aggregate into a multicellular structure and form a film; （2） bacteria multiply and grow; and （3） they decompose and diffuse to other locations， and then start from （1）[23]. Recent studies have shown that the bacterial QS system plays an important role in the formation of bacterial biofilms[24]. The specific mechanism is that after activation of the LuxS/AI-2 system， the Agr system is activated， and produces RNA III， which further binds to its target protein TRAP to promote the formation of SA biofilm[25]. The LuxS/AI-2 system can affect the ica pathway by acting on the icaR[26]， thereby affecting the formation and diffusion of biofilms; and the Agr system can also affect biofilms by affecting the ica pathway[27]， and can independently affect biofilms through the agrA pathway[28].
The Agr system plays an important role in the formation and diffusion of SA biofilms. Agr controls proteases， which affect the expansion of biofilms by degrading the protein components of the biofilm adhesin in vitro and increase the degree of diffusion of biofilms[29]. A small amount of PSM peptides produced by low-activity Agr interacts with the cell surface by interfering with biofilm adhesin PIA， making the bacterial aggregation grow into a large aggregation[30]. When the bacterial concentration is low， the Agr system will inhibit the formation of SA biofilms and increase the flow and quantity of SA， until the production of toxic factors at high concentrations， thereby promoting biofilm formation. Further research found that there are many factors on Agr that affect the formation of biofilms， such as CodY， SarA， etc.[31]. CodY is a negative regulator of the Agr system. CodY indirectly affects the RNA III transcription of the Agr system. The increase of CodY will lead to the accumulation of AIP III， which will reduce the biofilm formation[32]. SarA is one of the main factors affecting biofilm formation. Beenken et al.[33] pointed out that in the process of SA biofilm formation， agr is the superior of SarA， and agr will make SarA have more effect on the formation of biofilms. On the other hand， AI-2 inhibits the transcription level of kdpD and kdpE by acting on the binary signaling system KdpDE， which reduces the amount of kdpE bound to cap and reduces the production of capsular polysaccharides， thereby inhibiting the synthesis of biofilms[34]. Yu et al.[35] compared the amounts of biofilm produced in a LuxS-deleted SA strain， the LuxS-deleted SA strain added with different doses of DPD and normal SA strain， and found that the amount of biofilm of the LuxS-deleted SA strain after DPD addition was reduced. Further study on the expression levels of icaA and icaR genes in the LuxS-deleted SA strain after adding DPD found that AI-2 could inhibit the expression of icaADBC by activating icaR， thereby inhibiting biofilm formation.
The Effect of SAs QS System on SA Virulence Factor
In addition to being related to biofilms， the QS system of bacteria is mainly related to bacterial virulence. The most prominent of these is the Agr-regulated toxin， α-toxin （α-hemolysin， Hla） encoded by the hla locus. It is a β-barrel pore toxin composed of 319 amino acids that binds to disintegrin and metalloproteinase 10 （ADAM10） receptors on the host cell membrane[28-29]. Hla is related to multiple staphylococcal infections in the human body. In animal models of pneumonia infected with staphylococci[30-31]， skin and soft tissue infections[32-33] and intravascular infections[34]， hla gene-deleted mutants showed lower levels of pathogenicity than standard strains.
Phenol-soluble modulated peptide （PSM） is a family of peptide toxins. Among the virulence factors controlled by Agr， it is the only virulence factor directly controlled by AgrA[35]， which plays an important role in the non-infectious activities of Staphylococcus[36]. In the PSM class， among those encoded in the psmα locus of S. aureus， the most notable is PSMα3， which has a strong pro-inflammatory effect and solubility on a variety of cell types including neutrophils， macrophages， osteoblasts and red blood cells[37]. It results in PSMα peptides having a strong effect on acute S. aureus infections， such as skin and soft tissue infections， sepsis and osteomyelitis[38-39].
Conclusions and Discussion
With the increasing abuse of antibiotics in recent years， the resistance of S. aureus has become an increasingly difficult therapeutic obstacle， and the QS system of S. aureus has become a new and effective research direction. However， the QS system is very complicated. At present， the complete QS system of S. aureus has not been drawn， but existing studies have shown that the pathogenicity of S. aureus is closely related to its QS system， indicating that its antibacterial research in the future can be conducted to towards its own Agr QS system and its LuxS QS system. This paper reviewed the current QS system of S. aureus on biofilms and the current QS mechanism of S. aureus， laying a foundation for future research on the toxicity and drug resistance of S. aureus. References
[1] RASMUSSEN RV， JR FV， SKOV R， et al. Future challenges and treatment of Staphylococcus aureus bacteria with emphasis on MRSA[J]. Future Microbiology， 2011， 6（1）： 43-56.
[2] ROOIJAKKERS SH， VAN KESSEL KP， VAN STRIJP JA. Staphylococcal innate immune evasion[J]. Trends in Microbiology， 2005， 13（12）： 596-601.
[3] FUQUA WC， WINANS SC， GREENBERG EP. Quorum sensing in bacteria： the LuxR-LuxI family of cell density-responsive transcriptional regulators[J]. Journal of Bacteriology， 1994， 176（2）： 269.
[4] ENGEBRECHT J， NEALSON K， SILVERMAN M. Bacterial bioluminescence： Isolation and genetic analysis of functions from Vibrio fischeri[J]. Cell， 1983， 32（3）： 773.
[5] CAO JG， MEIGHEN EA. Purification and structural identification of an autoinducer for the luminescence system of Vibrio harveyi[J]. Journal of Biological Chemistry， 1989， 264（36）： 21670.
[6] YARWOOD JM， BARTELS DJ， VOLPER EM， et al. Quorum sensing in Staphylococcus aureus biofilms[J]. Journal of Bacteriology， 2004， 186（6）： 1838.
[7] SHU YQ， JAMESONLEE M， VILLARUZ AE， et al. RNAIII-independent target gene control by the quorum-sensing system： Insight into the evolution of virulence regulation in Staphylococcus aureus[J]. Molecular Cell， 2008， 32（1）： 150-158.
[8] CASTILLOJUáREZ I， MAEDA T， MANDUJANOTINOCO EA， et al. Role of quorum sensing in bacterial infections[J]. World Journal of Clinical Cases， 2015， 3（7）： 575.
[9] YU D， ZHAO L， XUE T， et al. Staphylococcus aureus， autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner[J]. Bmc Microbiology， 2012， 12（1）： 288.
[10] PENG HL， NOVICK RP， KREISWIRTH B， et al. Cloning， characterization， and sequencing of an accessory gene regulator （agr） in Staphylococcus aureus[J]. Journal of Bacteriology， 1988， 170（9）： 4365-4372.
[11] THOENDEL M， KAVANAUGH JS， FLACK CE， et al. Peptide signaling in the Staphylococci[J]. Chemical Reviews， 2011， 111（1）： 117-151.
[12] KORNBLUM J， KREISWIRTH B， PROJAN SJ， et al. Agr： a polycistronic locus regulating exoprotein synthesis in Staphylococcus aureus[J]. 1990： 373-402.
[13] BRIAN G， PAMELA H， HATTIE G. Targetingagr- and agr-like quorum sensing systems for development of common therapeutics to treat multiple gram-positive bacterial infections[J]. Sensors， 2013， 13（4）： 5130-5166.
[14] GEISINGER E， CHEN J， NOVICK RP. Allele-dependent differences in quorum-sensing dynamics result in variant expression of virulence genes in Staphylococcus aureus[J]. Journal of Bacteriology， 2012， 194（11）： 2854-64. [15] CHEUNG GY， JOO HS， CHATTERJEE SS， et al. Phenol-soluble modulins-critical determinants of staphylococcal virulence[J]. Fems Microbiology Reviews， 2014， 38（4）： 698-719.
[16] BASSLER BL， GREENBERG EP， STEVENS AM. Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi[J]. Journal of Bacteriology， 1997， 179（12）： 4043-4045.
[17] WINZER K， HARDIE K R， WILLIAMS P. LuxS and autoinducer-2： Their contribution to quorum sensing and metabolism in bacteria[J]. Advances in Applied Microbiology， 2003， 53（4）： 291.
[18] ZHAO LP. Regulation of AI-2 quorum sensing system in Staphylococcus aureus[D]. Hefei： University of Science and Technology of China， 2010. （in Chinese）
[19] XUE T， ZHAO LP， SUN BL. LuxS/AI-2 system is involved in antibiotic susceptibility and autolysi in Staphylococcus aureus NCTC 8325[J]. International Journal of Antimicrobial Agents， 2013， 41（1）： 85-9.
[20] YU D， ZHAO L， XUE T， et al. Staphylococcus aureus， autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner[J]. Bmc Microbiology， 2012， 12（1）： 288.
[21] COSTERTON JW， GEESEY GG， CHENG KJ. How bacteria stick[J]. Scientific American， 1978， 238（1）： 86-95.
[22] LI J， XIE S， AHMED S， et al. Antimicrobial activity and resistance： Influencing factors[J]. Frontiers in Pharmacology， 2017（8）： 364.
[23] PAHARIK AE， HORSWILL AR. The Staphylococcal biofilm： Adhesins， regulation， and host response[J]. Microbiology Spectrum， 2016， 4（2）： 10.
[24] TOWNSLEY L， SHANK EA. Natural-product antibiotics： Cues for modulating bacterial biofilm formation[J]. Trends in microbiology， 2017.
[25] KIRAN MD， ADIKESAVAN NV， CIRIONI O， et al. Discovery of a quorum-sensing inhibitor of drug-resistant staphylococcal infections by structure-based virtual screening.[J]. Molecular Pharmacology， 2008， 73（5）： 1578.
[26] DAN Y， ZHAO L， XUE T， et al. Staphylococcus aureus autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner[J]. Bmc Microbiology， 2012， 12（1）： 288.
[27] AUDRETSCH C. Quorum sensing and biofilm formation in Staphylococcus aureus[M]. Suedwestdeutscher Verlag Fuer Hochschulschriften， 2014.
[28] FOSTER TJ， GEOGHEGAN JA， GANESH VK， et al. Adhesion， invasion and evasion： the many functions of the surface proteins of Staphylococcus aureus[J]. Nature Reviews Microbiology， 2014， 12（1）： 49.
[29] LAUDERDALE KJ， BOLES BR， CHEUNG AL， et al. Interconnections between Sigma B， agr， and proteolytic activity in Staphylococcus aureus biofilm maturation[J]. Infection & Immunity， 2009， 77（4）： 1623-35. [30] DASTGHEYB SS， VILLARUZ AE， LE KY， et al. Role of phenol-soluble modulins in formation of Staphylococcus aureus biofilms in synovial fluid[J]. Infection & Immunity， 2015， 83（7）： 2966-75.
[31] RUTHERFORD ST， BASSLER BL. Bacterial quorum sensing： Its role in virulence and possibilities for its control[J]. Cold Spring Harbor Perspectives in Medicine， 2012， 2（11）： 705-709.
[32] ROUX A， TODD DA， VELáZQUEZ JV， et al. CodY-Mediated regulation of the Staphylococcus aureus Agr system integrates nutritional and population density signals[J]. Journal of Bacteriology， 2014， 196（6）： 1184-96.
[33] BEENKEN KE， MRAK LN， GRIFFIN LM， et al. Epistatic relationships between sarA and agr in Staphylococcus aureus biofilm formation[J]. Plos One， 2010， 5（5）： e10790.
[34] ZHAO L， XUE T， SHANG F， et al. Staphylococcus aureus AI-2 quorum sensing associates with the KdpDE two-component system to regulate capsular polysaccharide synthesis and virulence[J]. Infection & Immunity， 2010， 78（8）： 3506.
[35] YU D， ZHAO L， XUE T， et al. Staphylococcus aureus， autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner[J]. Bmc Microbiology， 2012， 12（1）： 288.
[36] CHEUNG GY， JOO HS， CHATTERJEE SS， et al. Phenol-soluble modulins-critical determinants of staphylococcal virulence[J]. FEMS Microbiol. Rev.， 2014（38）： 698-719.
[37] RASIGADE JP， TROUILLET-ASSANT S， FERRY T， et al. PSMs of hypervirulent Staphylococcus aureus act as intracellular toxins that kill infected osteoblasts[J]. PLoS ONE， 2013（8）： e63176.
[38] WANG R， BRAUGHTON KR， KRETSCHMER D， et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA[J]. Nat. Med.， 2007（13）： 1510-1514.
[39] CASSAT JE， HAMMER ND， CAMPBELL JP， et al. A secreted bacterial protease tailors the Staphylococcus aureus virulence repertoire to modulate bone remodeling during osteomyelitis[J]. Cell Host Microbe， 2013（13）： 759-772.
Key words Quorum sensing; Staphylococcus aureus; Biofilm; Pathogenicity
Staphylococcus aureus （SA） is a common pathogen causing community- and hospital-acquired infections. It is the main cause of human blood infections and can infect various organs to cause infective endocarditis， suppurative arthritis， and osteomyelitis[1]. SA is also very good at evading the hosts immune system， and constantly develops resistance to antibiotics[2]， which poses a great obstacle to treatment.
The phenomenon of bacteria regulating a series of genes through the sensing of signaling molecules in the environment is called the quorum sensing （QS）， also known as self-induction[3]. Instead of language， bacteria use certain secondary metabolites secreted by themselves as signal molecules. When the bacteria reach a certain threshold concentration， the bacteria generate some gene expression by recognizing these signal molecules， resulting in a series of physiological changes[4-5].
Current experiments have shown that SAs QS system is closely related to SAs toxicity and drug resistance[6-7]. Therefore， interfering with SAs QS system to treat SA infection has become an emerging research hotspot[8]. This paper reviewed the research progress of SAs QS system in recent years.
SAs QS Regulation Network
For SA， at least two QS systems have been currently found， which are divided into the agr systems with autoinducing peptides （AIPs） as signal molecules[9] and the LuxS/AI-2 system with furanosyl borate diester （AI-2） as s signal molecule according to the types of signal molecules[10].
The Agr system is a known QS system in the genus Staphylococcus， which is closely related to the synthesis of SAs toxic factors and cell surface adhesion[11]. The agr locus is 3.5 kb in size and consists of two different transcription units， RNA II and RNA III， which are activated by P2 and P3 promoters， respectively[12]. The RNA II locus contains four genes， agrB， agrD， agrC and agrA. agrD is responsible for encoding extracellular pre-peptides AIPs that can be used as QS signal molecules of agr; the gene product of agrB is a transmembrane endopeptidase， used to introduce lactone modification， C-terminal cleavage and outflow of AIPs; and the agrC and agrA genes encode a two-component signal transduction system， including a histidine kinase sensor AgrC， a transmembrane protein that can bind and phosphorylate AIPs and its associated response regulator AgrA[13]. After phosphorylation activation of AgrC， AgrA binds the P2 promoter region on RNA II and the P3 promoter region on RNA III[14]， and further activates RNA III， which is then translated to produce δ toxin encoded by hld[15]. The LuxS/AI-2 system is a QS system with furanosyl borate diester （AI-2） as a signal molecule. It was first discovered from Vibrio harveyi[16]， and later found to be widespread in most bacteria. The QS system is presumed to be a common language among strains[17]. AI-2 is a by-product of the bacterial methyl cycle. In the methyl cycle， s-adenosylmethionine （SAM） is converted to S-adenosylhomocysteine （SAH）， which is hydrolyzed by 5′-methylthioadenosine/S-adenosylhomocysteinase （Pfs） into S-ribose homocysteine （SRH） and adenine， and then the AI-2 anabolic enzyme LuxS catalyzes SRH into the precursor compound of AI-2， 4，5-dihydroxy-2，3-pentanedione， i.e.， DPD， which is unstable itself， and is further converted into AI-2[18]. AI-2 is closely related to various pathogenicity of SA， such as biofilm formation， sensitivity to antibiotics， and toxicity[19-20].
The Effect of SAs QS System on SA Biofilm
The concept of bacterial biofilm was first proposed by Costerton et al.[21] in 1978. After a lot of research and summary， the academic community generally believes that a bacterial biofilm is a polysaccharide complex secreted by bacteria in order to adapt to the environment， which attaches to the surface of the contact object， and protects the bacteria in the film from antibacterial drugs， while secreting antibiotic inactivating enzymes， which greatly reduce the effects of antibacterial drugs[22]. The biofilm formation process is mainly divided into several steps： （1） bacteria adhere to the surface of non-living things or host matrix proteins， and then aggregate into a multicellular structure and form a film; （2） bacteria multiply and grow; and （3） they decompose and diffuse to other locations， and then start from （1）[23]. Recent studies have shown that the bacterial QS system plays an important role in the formation of bacterial biofilms[24]. The specific mechanism is that after activation of the LuxS/AI-2 system， the Agr system is activated， and produces RNA III， which further binds to its target protein TRAP to promote the formation of SA biofilm[25]. The LuxS/AI-2 system can affect the ica pathway by acting on the icaR[26]， thereby affecting the formation and diffusion of biofilms; and the Agr system can also affect biofilms by affecting the ica pathway[27]， and can independently affect biofilms through the agrA pathway[28].
The Agr system plays an important role in the formation and diffusion of SA biofilms. Agr controls proteases， which affect the expansion of biofilms by degrading the protein components of the biofilm adhesin in vitro and increase the degree of diffusion of biofilms[29]. A small amount of PSM peptides produced by low-activity Agr interacts with the cell surface by interfering with biofilm adhesin PIA， making the bacterial aggregation grow into a large aggregation[30]. When the bacterial concentration is low， the Agr system will inhibit the formation of SA biofilms and increase the flow and quantity of SA， until the production of toxic factors at high concentrations， thereby promoting biofilm formation. Further research found that there are many factors on Agr that affect the formation of biofilms， such as CodY， SarA， etc.[31]. CodY is a negative regulator of the Agr system. CodY indirectly affects the RNA III transcription of the Agr system. The increase of CodY will lead to the accumulation of AIP III， which will reduce the biofilm formation[32]. SarA is one of the main factors affecting biofilm formation. Beenken et al.[33] pointed out that in the process of SA biofilm formation， agr is the superior of SarA， and agr will make SarA have more effect on the formation of biofilms. On the other hand， AI-2 inhibits the transcription level of kdpD and kdpE by acting on the binary signaling system KdpDE， which reduces the amount of kdpE bound to cap and reduces the production of capsular polysaccharides， thereby inhibiting the synthesis of biofilms[34]. Yu et al.[35] compared the amounts of biofilm produced in a LuxS-deleted SA strain， the LuxS-deleted SA strain added with different doses of DPD and normal SA strain， and found that the amount of biofilm of the LuxS-deleted SA strain after DPD addition was reduced. Further study on the expression levels of icaA and icaR genes in the LuxS-deleted SA strain after adding DPD found that AI-2 could inhibit the expression of icaADBC by activating icaR， thereby inhibiting biofilm formation.
The Effect of SAs QS System on SA Virulence Factor
In addition to being related to biofilms， the QS system of bacteria is mainly related to bacterial virulence. The most prominent of these is the Agr-regulated toxin， α-toxin （α-hemolysin， Hla） encoded by the hla locus. It is a β-barrel pore toxin composed of 319 amino acids that binds to disintegrin and metalloproteinase 10 （ADAM10） receptors on the host cell membrane[28-29]. Hla is related to multiple staphylococcal infections in the human body. In animal models of pneumonia infected with staphylococci[30-31]， skin and soft tissue infections[32-33] and intravascular infections[34]， hla gene-deleted mutants showed lower levels of pathogenicity than standard strains.
Phenol-soluble modulated peptide （PSM） is a family of peptide toxins. Among the virulence factors controlled by Agr， it is the only virulence factor directly controlled by AgrA[35]， which plays an important role in the non-infectious activities of Staphylococcus[36]. In the PSM class， among those encoded in the psmα locus of S. aureus， the most notable is PSMα3， which has a strong pro-inflammatory effect and solubility on a variety of cell types including neutrophils， macrophages， osteoblasts and red blood cells[37]. It results in PSMα peptides having a strong effect on acute S. aureus infections， such as skin and soft tissue infections， sepsis and osteomyelitis[38-39].
Conclusions and Discussion
With the increasing abuse of antibiotics in recent years， the resistance of S. aureus has become an increasingly difficult therapeutic obstacle， and the QS system of S. aureus has become a new and effective research direction. However， the QS system is very complicated. At present， the complete QS system of S. aureus has not been drawn， but existing studies have shown that the pathogenicity of S. aureus is closely related to its QS system， indicating that its antibacterial research in the future can be conducted to towards its own Agr QS system and its LuxS QS system. This paper reviewed the current QS system of S. aureus on biofilms and the current QS mechanism of S. aureus， laying a foundation for future research on the toxicity and drug resistance of S. aureus. References
[1] RASMUSSEN RV， JR FV， SKOV R， et al. Future challenges and treatment of Staphylococcus aureus bacteria with emphasis on MRSA[J]. Future Microbiology， 2011， 6（1）： 43-56.
[2] ROOIJAKKERS SH， VAN KESSEL KP， VAN STRIJP JA. Staphylococcal innate immune evasion[J]. Trends in Microbiology， 2005， 13（12）： 596-601.
[3] FUQUA WC， WINANS SC， GREENBERG EP. Quorum sensing in bacteria： the LuxR-LuxI family of cell density-responsive transcriptional regulators[J]. Journal of Bacteriology， 1994， 176（2）： 269.
[4] ENGEBRECHT J， NEALSON K， SILVERMAN M. Bacterial bioluminescence： Isolation and genetic analysis of functions from Vibrio fischeri[J]. Cell， 1983， 32（3）： 773.
[5] CAO JG， MEIGHEN EA. Purification and structural identification of an autoinducer for the luminescence system of Vibrio harveyi[J]. Journal of Biological Chemistry， 1989， 264（36）： 21670.
[6] YARWOOD JM， BARTELS DJ， VOLPER EM， et al. Quorum sensing in Staphylococcus aureus biofilms[J]. Journal of Bacteriology， 2004， 186（6）： 1838.
[7] SHU YQ， JAMESONLEE M， VILLARUZ AE， et al. RNAIII-independent target gene control by the quorum-sensing system： Insight into the evolution of virulence regulation in Staphylococcus aureus[J]. Molecular Cell， 2008， 32（1）： 150-158.
[8] CASTILLOJUáREZ I， MAEDA T， MANDUJANOTINOCO EA， et al. Role of quorum sensing in bacterial infections[J]. World Journal of Clinical Cases， 2015， 3（7）： 575.
[9] YU D， ZHAO L， XUE T， et al. Staphylococcus aureus， autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner[J]. Bmc Microbiology， 2012， 12（1）： 288.
[10] PENG HL， NOVICK RP， KREISWIRTH B， et al. Cloning， characterization， and sequencing of an accessory gene regulator （agr） in Staphylococcus aureus[J]. Journal of Bacteriology， 1988， 170（9）： 4365-4372.
[11] THOENDEL M， KAVANAUGH JS， FLACK CE， et al. Peptide signaling in the Staphylococci[J]. Chemical Reviews， 2011， 111（1）： 117-151.
[12] KORNBLUM J， KREISWIRTH B， PROJAN SJ， et al. Agr： a polycistronic locus regulating exoprotein synthesis in Staphylococcus aureus[J]. 1990： 373-402.
[13] BRIAN G， PAMELA H， HATTIE G. Targetingagr- and agr-like quorum sensing systems for development of common therapeutics to treat multiple gram-positive bacterial infections[J]. Sensors， 2013， 13（4）： 5130-5166.
[14] GEISINGER E， CHEN J， NOVICK RP. Allele-dependent differences in quorum-sensing dynamics result in variant expression of virulence genes in Staphylococcus aureus[J]. Journal of Bacteriology， 2012， 194（11）： 2854-64. [15] CHEUNG GY， JOO HS， CHATTERJEE SS， et al. Phenol-soluble modulins-critical determinants of staphylococcal virulence[J]. Fems Microbiology Reviews， 2014， 38（4）： 698-719.
[16] BASSLER BL， GREENBERG EP， STEVENS AM. Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi[J]. Journal of Bacteriology， 1997， 179（12）： 4043-4045.
[17] WINZER K， HARDIE K R， WILLIAMS P. LuxS and autoinducer-2： Their contribution to quorum sensing and metabolism in bacteria[J]. Advances in Applied Microbiology， 2003， 53（4）： 291.
[18] ZHAO LP. Regulation of AI-2 quorum sensing system in Staphylococcus aureus[D]. Hefei： University of Science and Technology of China， 2010. （in Chinese）
[19] XUE T， ZHAO LP， SUN BL. LuxS/AI-2 system is involved in antibiotic susceptibility and autolysi in Staphylococcus aureus NCTC 8325[J]. International Journal of Antimicrobial Agents， 2013， 41（1）： 85-9.
[20] YU D， ZHAO L， XUE T， et al. Staphylococcus aureus， autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner[J]. Bmc Microbiology， 2012， 12（1）： 288.
[21] COSTERTON JW， GEESEY GG， CHENG KJ. How bacteria stick[J]. Scientific American， 1978， 238（1）： 86-95.
[22] LI J， XIE S， AHMED S， et al. Antimicrobial activity and resistance： Influencing factors[J]. Frontiers in Pharmacology， 2017（8）： 364.
[23] PAHARIK AE， HORSWILL AR. The Staphylococcal biofilm： Adhesins， regulation， and host response[J]. Microbiology Spectrum， 2016， 4（2）： 10.
[24] TOWNSLEY L， SHANK EA. Natural-product antibiotics： Cues for modulating bacterial biofilm formation[J]. Trends in microbiology， 2017.
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