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金黄色葡萄球菌群体感应系统及毒力调控机制
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Abstract:
辅助基因调控(agr)群体感应系统通过调控毒力因子及生物被膜形成等影响金黄色葡萄球菌毒力的表达。agr的信号传导主要依赖于自诱导信号肽(AIP)与AgrC结合后激活AgrA，而后直接由AgrA或转录后调节因子RNAIII作用于下游靶基因调控金黄色葡萄球菌的毒力因子。本综述主要讲述了AIP与AgrC结合以及AgrA作用于下游靶基因的机制。讨论了agr阴性突变菌株感染对临床患者的影响，还讨论了多种毒力调控基因与agr共同作用调节金葡菌毒力的复杂网络。
Accessory gene regulator (agr) quorum sensing network affects the expression of Staphylococcus aureus virulence by regulating virulence factors and biofilm formation. The signal transduction of agr mainly depends on the activation of AgrA after the binding of AIP with AgrC, and then the direct action of AgrA or the post-transcriptional regulatory factor RNAIII on the downstream target gene to regulate the virulence factors of Staphylococcus aureus. This review mainly describes the mechanism of AIP binding to AgrC and AgrA acting on downstream target genes. The effects of agr negative mutant strains on clinical patients were discussed, and the complex network of virulence regulation genes and agr regulating Staphylococcus aureus was discussed.
| [1] | Cheung, G.Y.C., Bae, J.S. and Otto, M. (2021) Pathogenicity and Virulence of staphylococcus Aureus. Virulence, 12, 547-569. https://doi.org/10.1080/21505594.2021.1878688 |
| [2] | Janzon, L. and Arvidson, S. (1990) The Role of the Delta-Lysin Gene (hld) in the Regulation of Virulence Genes by the Accessory Gene Regulator (agr) in Staphylococcus Aureus. The EMBO Journal, 9, 1391-1399. https://doi.org/10.1002/j.1460-2075.1990.tb08254.x |
| [3] | Novick, R.P. and Geisinger, E. (2008) Quorum Sensing in Staphylococci. Annual Review of Genetics, 42, 541-564. https://doi.org/10.1146/annurev.genet.42.110807.091640 |
| [4] | Arvidson, S. and Tegmark, K. (2001) Regulation of Virulence Determinants in Staphylococcus Aureus. International Journal of Medical Microbiology, 291, 159-170. https://doi.org/10.1078/1438-4221-00112 |
| [5] | Thoendel, M. and Horswill, A.R. (2009) Identification of Staphylococcus aureus AgrD Residues Required for Autoinducing Peptide Biosynthesis. Journal of Biological Chemistry, 284, 21828-21838. https://doi.org/10.1074/jbc.m109.031757 |
| [6] | MDowell, P., Affas, Z., Reynolds, C., Holden, M.T.G., Wood, S.J., Saint, S., et al. (2001) Structure, Activity and Evolution of the Group I Thiolactone Peptide Quorum-Sensing System of Staphylococcus aureus. Molecular Microbiology, 41, 503-512. https://doi.org/10.1046/j.1365-2958.2001.02539.x |
| [7] | Ji, G., Beavis, R. and Novick, R.P. (1997) Bacterial Interference Caused by Autoinducing Peptide Variants. Science, 276, 2027-2030. https://doi.org/10.1126/science.276.5321.2027 |
| [8] | Zhang, L. and Ji, G. (2004) Identification of a Staphylococcal AgrB Segment(s) Responsible for Group-Specific Processing of AgrD by Gene Swapping. Journal of Bacteriology, 186, 6706-6713. https://doi.org/10.1128/jb.186.20.6706-6713.2004 |
| [9] | Dufour, P., Jarraud, S., Vandenesch, F., Greenland, T., Novick, R.P., Bes, M., et al. (2002) High Genetic Variability of the agr Locus in staphylococcus Species. Journal of Bacteriology, 184, 1180-1186. https://doi.org/10.1128/jb.184.4.1180-1186.2002 |
| [10] | Jensen, R.O., Winzer, K., Clarke, S.R., Chan, W.C. and Williams, P. (2008) Differential Recognition of Staphylococcus aureus Quorum-Sensing Signals Depends on Both Extracellular Loops 1 and 2 of the Transmembrane Sensor AgrC. Journal of Molecular Biology, 381, 300-309. https://doi.org/10.1016/j.jmb.2008.06.018 |
| [11] | Ji, G., Pei, W., Zhang, L., Qiu, R., Lin, J., Benito, Y., et al. (2005) staphylococcus Intermedius Produces a Functional agr Autoinducing Peptide Containing a Cyclic Lactone. Journal of Bacteriology, 187, 3139-3150. https://doi.org/10.1128/jb.187.9.3139-3150.2005 |
| [12] | Reynolds, J. and Wigneshweraraj, S. (2011) Molecular Insights into the Control of Transcription Initiation at the Staphylococcus Aureus agr Operon. Journal of Molecular Biology, 412, 862-881. https://doi.org/10.1016/j.jmb.2011.06.018 |
| [13] | Novick, R.P., Projan, S.J., Kornblum, J., Ross, H.F., Ji, G., Kreiswirth, B., et al. (1995) The agr P2 Operon: An Autocatalytic Sensory Transduction System in Staphylococcus aureus. Molecular and General Genetics, 248, 446-458. https://doi.org/10.1007/bf02191645 |
| [14] | Queck, S.Y., Jameson-Lee, M., Villaruz, A.E., Bach, T.L., Khan, B.A., Sturdevant, D.E., et al. (2008) RNAIII-Independent Target Gene Control by the agr Quorum-Sensing System: Insight into the Evolution of Virulence Regulation in Staphylococcus Aureus. Molecular Cell, 32, 150-158. https://doi.org/10.1016/j.molcel.2008.08.005 |
| [15] | Morfeldt, E., Taylor, D., von Gabain, A. and Arvidson, S. (1995) Activation of Alpha-Toxin Translation in Staphylococcus Aureus by the Trans-Encoded Antisense RNA, RNAIII. The EMBO Journal, 14, 4569-4577. https://doi.org/10.1002/j.1460-2075.1995.tb00136.x |
| [16] | Xiong, Y., Van Wamel, W., Nast, C.C., Yeaman, M.R., Cheung, A.L. and Bayer, A.S. (2002) Activation and Transcriptional Interaction between agr RNAII and RNAIII in Staphylococcus aureus in Vitro and in an Experimental Endocarditis Model. The Journal of Infectious Diseases, 186, 668-677. https://doi.org/10.1086/342046 |
| [17] | Sloan, T.J., Murray, E., Yokoyama, M., Massey, R.C., Chan, W.C., Bonev, B.B., et al. (2019) Timing Is Everything: Impact of Naturally Occurring staphylococcus Aureus AgrC Cytoplasmic Domain Adaptive Mutations on Autoinduction. Journal of Bacteriology, 201, e00409-19. https://doi.org/10.1128/jb.00409-19 |
| [18] | Young, B.C., Wu, C., Gordon, N.C., Cole, K., Price, J.R., Liu, E., et al. (2017) Severe Infections Emerge from Commensal Bacteria by Adaptive Evolution. E Life, 6, e30637. https://doi.org/10.7554/elife.30637 |
| [19] | Yang, X., Dong, F., Qian, S., Wang, L., Liu, Y., Yao, K., et al. (2019) Accessory Gene Regulator (agr) Dysfunction Was Unusual in Staphylococcus Aureus Isolated from Chinese Children. BMC Microbiology, 19, Article No. 95. https://doi.org/10.1186/s12866-019-1465-z |
| [20] | Jiang, S., Chen, M., Zhang, J., Ba, X., Zhang, H., Hong, Y., et al. (2023) Profiling Daptomycin Resistance among Diverse Methicillin-Resistant Staphylococcus aureus Lineages in China. Antimicrobial Agents and Chemotherapy, 67, e0056323. https://doi.org/10.1128/aac.00563-23 |
| [21] | Chong, Y.P., Kim, E.S., Park, S., Park, K., Kim, T., Kim, M., et al. (2013) Accessory Gene Regulator (agr) Dysfunction in Staphylococcus aureus Bloodstream Isolates from South Korean Patients. Antimicrobial Agents and Chemotherapy, 57, 1509-1512. https://doi.org/10.1128/aac.01260-12 |
| [22] | Cameron, D.R., Howden, B.P. and Peleg, A.Y. (2011) The Interface between Antibiotic Resistance and Virulence in Staphylococcus aureus and Its Impact Upon Clinical Outcomes. Clinical Infectious Diseases, 53, 576-582. https://doi.org/10.1093/cid/cir473 |
| [23] | Schweizer, M.L., Furuno, J.P., Sakoulas, G., Johnson, J.K., Harris, A.D., Shardell, M.D., et al. (2011) Increased Mortality with Accessory Gene Regulator (agr) Dysfunction in Staphylococcus aureus among Bacteremic Patients. Antimicrobial Agents and Chemotherapy, 55, 1082-1087. https://doi.org/10.1128/aac.00918-10 |
| [24] | Scherr, T.D., Hanke, M.L., Huang, O., James, D.B.A., Horswill, A.R., Bayles, K.W., et al. (2015) Staphylococcus aureus Biofilms Induce Macrophage Dysfunction through Leukocidin AB and Alpha-Toxin. mBio, 6, e01021-15. https://doi.org/10.1128/mbio.01021-15 |
| [25] | Häffner, N., Bär, J., Dengler Haunreiter, V., Mairpady Shambat, S., Seidl, K., Crosby, H.A., et al. (2020) Intracellular Environment and agr System Affect Colony Size Heterogeneity of Staphylococcus aureus. Frontiers in Microbiology, 11, Article 01415. https://doi.org/10.3389/fmicb.2020.01415 |
| [26] | Gor, V., Takemura, A.J., Nishitani, M., Higashide, M., Medrano Romero, V., Ohniwa, R.L., et al. (2019) Finding of agr Phase Variants in Staphylococcus aureus. mBio, 10, e00796-19. https://doi.org/10.1128/mbio.00796-19 |
| [27] | Morfeldt, E., Tegmark, K. and Arvidson, S. (1996) Transcriptional Control of the agr-Dependent Virulence Gene Regulator, RNAIII, in Staphylococcus aureus. Molecular Microbiology, 21, 1227-1237. https://doi.org/10.1046/j.1365-2958.1996.751447.x |
| [28] | Cheung, A.L., Bayer, A.S., Zhang, G., Gresham, H. and Xiong, Y. (2004) Regulation of Virulence Determinants in Vitro and in Vivo in Staphylococcus aureus. FEMS Immunology & Medical Microbiology, 40, 1-9. https://doi.org/10.1016/s0928-8244(03)00309-2 |
| [29] | Bayer, M.G., Heinrichs, J.H. and Cheung, A.L. (1996) The Molecular Architecture of the Sar Locus in Staphylococcus aureus. Journal of Bacteriology, 178, 4563-4570. https://doi.org/10.1128/jb.178.15.4563-4570.1996 |
| [30] | Liu, Y., Manna, A.C., Pan, C., Kriksunov, I.A., Thiel, D.J., Cheung, A.L., et al. (2006) Structural and Function Analyses of the Global Regulatory Protein Sara from Staphylococcus aureus. Proceedings of the National Academy of Sciences, 103, 2392-2397. https://doi.org/10.1073/pnas.0510439103 |
| [31] | Roberts, C., Anderson, K.L., Murphy, E., Projan, S.J., Mounts, W., Hurlburt, B., et al. (2006) Characterizing the Effect of Thestaphylococcus Aureusvirulence Factor Regulator, Sara, on Log-Phase mRNA Half-Lives. Journal of Bacteriology, 188, 2593-2603. https://doi.org/10.1128/jb.188.7.2593-2603.2006 |
| [32] | Chan, P.F., Foster, S.J., Ingham, E. and Clements, M.O. (1998) The Staphylococcus aureus Alternative Sigma Factor Σ b Controls the Environmental Stress Response but Not Starvation Survival or Pathogenicity in a Mouse Abscess Model. Journal of Bacteriology, 180, 6082-6089. https://doi.org/10.1128/jb.180.23.6082-6089.1998 |
| [33] | Tegmark, K., Karlsson, A. and Arvidson, S. (2000) Identification and Characterization of Sarh1, a New Global Regulator of Virulence Gene Expression in Staphylococcus aureus. Molecular Microbiology, 37, 398-409. https://doi.org/10.1046/j.1365-2958.2000.02003.x |
| [34] | Cheung, A.L., Schmidt, K., Bateman, B. and Manna, A.C. (2001) Sars, a Sara Homolog Repressible by agr, Is an Activator of Protein a Synthesis in Staphylococcus aureus. Infection and Immunity, 69, 2448-2455. https://doi.org/10.1128/iai.69.4.2448-2455.2001 |
| [35] | Kaito, C., Morishita, D., Matsumoto, Y., Kurokawa, K. and Sekimizu, K. (2006) Novel DNA Binding Protein SarZ Contributes to Virulence in Staphylococcus aureus. Molecular Microbiology, 62, 1601-1617. https://doi.org/10.1111/j.1365-2958.2006.05480.x |
| [36] | Goerke, C., Campana, S., Bayer, M.G., Döring, G., Botzenhart, K. and Wolz, C. (2000) Direct Quantitative Transcript Analysis of the agr Regulon of Staphylococcus aureus during Human Infection in Comparison to the Expression Profile in Vitro. Infection and Immunity, 68, 1304-1311. https://doi.org/10.1128/iai.68.3.1304-1311.2000 |
| [37] | Yarwood, J.M., McCormick, J.K., Paustian, M.L., Kapur, V. and Schlievert, P.M. (2002) Repression of the Staphylococcus aureus Accessory Gene Regulator in Serum and in Vivo. Journal of Bacteriology, 184, 1095-1101. https://doi.org/10.1128/jb.184.4.1095-1101.2002 |
| [38] | Giraudo, A.T., Raspanti, C.G., Calzolari, A. and Nagel, R. (1994) Characterization of a Tn551-Mutant of Staphylococcus aureus Defective in the Production of Several Exoproteins. Canadian Journal of Microbiology, 40, 677-681. https://doi.org/10.1139/m94-107 |
| [39] | Giraudo, A.T., Cheung, A.L. and Nagel, R. (1997) The Sae Locus of Staphylococcus aureus Controls Exoprotein Synthesis at the Transcriptional Level. Archives of Microbiology, 168, 53-58. https://doi.org/10.1007/s002030050469 |
| [40] | Goerke, C., Fluckiger, U., Steinhuber, A., Zimmerli, W. and Wolz, C. (2001) Impact of the Regulatory Loci agr, sara and sae of Staphylococcus aureus on the Induction of α-Toxin during Device-Related Infection Resolved by Direct Quantitative Transcript Analysis. Molecular Microbiology, 40, 1439-1447. https://doi.org/10.1046/j.1365-2958.2001.02494.x |
| [41] | McNamara, P.J., Milligan-Monroe, K.C., Khalili, S. and Proctor, R.A. (2000) Identification, Cloning, and Initial Characterization of Rot, a Locus Encoding a Regulator of Virulence Factor Expression in Staphylococcus aureus. Journal of Bacteriology, 182, 3197-3203. https://doi.org/10.1128/jb.182.11.3197-3203.2000 |
