journal article·2025-09Open access

Quorum Sensing Inhibits Type III‐A CRISPR‐Cas System Activity Through Repressing Positive Regulators SarA and ArcR in Staphylococcus Aureus

Yang Li, Yuanyue Tang, Xiaofei Li, Nina Molin Høyland‐Kroghsbo, Hanne Ingmer, Xinan Jiao, Qiuchun Li

Advanced Science· Volume 12· Issue 36

Abstract

Abstract CRISPR‐Cas is an adaptive immune system that protects prokaryotes from the invasion of foreign genetic elements. The components and immunity mechanisms of CRISPR‐Cas have been extensively studied, but the regulation of this system in Staphylococci remains unclear. Here, it is shown that the cell‐cell communication, known as quorum sensing (QS), inhibits the expression and activity of the type III‐A CRISPR‐Cas system in S. aureus . The QS regulator, AgrA, directly binds to the promoters of two transcriptional regulators encoding the genes sarA and arcR to inhibit their expression. However, both SarA and ArcR act as positive regulators that promote the transcription of cas genes by directly binding to a novel promoter P cas . Furthermore, the P cas of 300 bp located in cas1 displays as a critical regulatory node to initiate the transcription of cas10 and csm3 . Our data reveal a new regulatory mechanism for QS‐mediated repression of the Type III‐A CRISPR‐Cas system, which may allow S. aureus to acquire foreign genetic elements encoding antibiotic resistance or virulence factors specifically at high cell density.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: CRISPR and Genetic Engineering · Bacterial Genetics and Biotechnology · Bacterial biofilms and quorum sensing

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Jiangsu Key Lab of Zoonosis/Jiangsu Co‐Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou University Jiangsu 225100 China

Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri‐food Safety and Quality Ministry of Agriculture of China Yangzhou University Jiangsu 225100 China

Department of Plant and Environmental Sciences University of Copenhagen Copenhagen 1870 Denmark

Department of Veterinary and Animal Sciences University of Copenhagen Copenhagen 1870 Denmark

Joint International Research Laboratory of Agriculture and Agri‐Product Safety Yangzhou University Jiangsu 225100 China

Funding

National Key Research and Development Program of China · Natural Science Foundation of Jiangsu Province · National Natural Science Foundation of China · Lundbeck Foundation · Priority Academic Program Development of Jiangsu Higher Education Institutions

References (85)

Show source-provided references
1. 10.1038/nrmicro356410.1038/nrmicro3564 ↗
2. 10.1038/s41586-019-1894-810.1038/s41586-019-1894-8 ↗
3. 10.1126/science.113814010.1126/science.1138140 ↗
4. 10.1126/science.116577110.1126/science.1165771 ↗
5. 10.1038/s41579-019-0299-x10.1038/s41579-019-0299-x ↗
6. 10.1038/nature1538610.1038/nature15386 ↗
7. 10.1038/nature1423710.1038/nature14237 ↗
8. 10.1093/nar/gks21610.1093/nar/gks216 ↗
9. 10.1101/gad.174290810.1101/gad.1742908 ↗
10. 10.1126/science.115968910.1126/science.1159689 ↗
11. 10.1038/nature0952310.1038/nature09523 ↗
12. 10.1038/nature1363710.1038/nature13637 ↗
13. 10.1016/j.cell.2015.04.02710.1016/j.cell.2015.04.027 ↗
14. 10.1111/mmi.1215210.1111/mmi.12152 ↗
15. 10.1101/gad.272153.11510.1101/gad.272153.115 ↗
16. 10.1101/gad.273722.11510.1101/gad.273722.115 ↗
17. 10.1016/j.molcel.2016.03.02410.1016/j.molcel.2016.03.024 ↗
18. 10.1126/science.aao010010.1126/science.aao0100 ↗
19. 10.1038/nature2346710.1038/nature23467 ↗
20. 10.1016/j.micres.2016.09.00310.1016/j.micres.2016.09.003 ↗
21. 10.1089/crispr.2021.004610.1089/crispr.2021.0046 ↗
22. 10.1016/j.ijmm.2016.08.00510.1016/j.ijmm.2016.08.005 ↗
23. 10.1038/s41589-020-00700-710.1038/s41589-020-00700-7 ↗
24. 10.1016/j.mib.2017.02.00410.1016/j.mib.2017.02.004 ↗
25. 10.1016/j.molcel.2016.11.01210.1016/j.molcel.2016.11.012 ↗
26. 10.1073/pnas.161741511310.1073/pnas.1617415113 ↗
27. 10.1128/AEM.01043-1510.1128/AEM.01043-15 ↗
28. 10.3389/fvets.2022.79941410.3389/fvets.2022.799414 ↗
29. 10.3389/fmicb.2022.98765610.3389/fmicb.2022.987656 ↗
30. 10.1038/s41396-021-00946-610.1038/s41396-021-00946-6 ↗
31. 10.1128/mBio.00627-1510.1128/mBio.00627-15 ↗
32. 10.1128/mBio.00362-1210.1128/mBio.00362-12 ↗
33. 10.1016/j.celrep.2023.11315410.1016/j.celrep.2023.113154 ↗
34. 10.1073/pnas.92.26.1205510.1073/pnas.92.26.12055 ↗
35. 10.1074/jbc.M20536720010.1074/jbc.M205367200 ↗
36. 10.1016/j.tim.2014.09.00210.1016/j.tim.2014.09.002 ↗
37. 10.1002/j.1460-2075.1993.tb06074.x10.1002/j.1460-2075.1993.tb06074.x ↗
38. 10.1016/j.molcel.2008.08.00510.1016/j.molcel.2008.08.005 ↗
39. 10.1002/j.1460-2075.1993.tb06074.x10.1002/j.1460-2075.1993.tb06074.x ↗
40. 10.1074/jbc.274.52.3716910.1074/jbc.274.52.37169 ↗
41. 10.1128/JB.00592-0710.1128/JB.00592-07 ↗
42. 10.1128/mbio.03174-2110.1128/mbio.03174-21 ↗
43. 10.1021/acsomega.1c0717810.1021/acsomega.1c07178 ↗
44. 10.1111/j.1365-2958.2010.07073.x10.1111/j.1365-2958.2010.07073.x ↗
45. 10.1128/JB.186.22.7549-7555.200410.1128/JB.186.22.7549-7555.2004 ↗
46. 10.1093/nar/gkl73410.1093/nar/gkl734 ↗
47. 10.1128/JB.185.15.4410-4417.200310.1128/JB.185.15.4410-4417.2003 ↗
48. 10.1128/msystems.00713-2110.1128/msystems.00713-21 ↗
49. Mauro T. · Nucleic Acids Res. · 2016 · 44
50. 10.1128/IAI.00046-1110.1128/IAI.00046-11 ↗
51. 10.3201/eid1604.09143510.3201/eid1604.091435 ↗
52. 10.1016/j.molcel.2016.08.03810.1016/j.molcel.2016.08.038 ↗
53. 10.3390/ijms1805096010.3390/ijms18050960 ↗
54. 10.1016/j.tim.2004.11.00910.1016/j.tim.2004.11.009 ↗
55. 10.1038/s41579-019-0186-510.1038/s41579-019-0186-5 ↗
56. 10.1126/science.280.5361.29510.1126/science.280.5361.295 ↗
57. 10.1371/journal.ppat.100005210.1371/journal.ppat.1000052 ↗
58. 10.1007/s00018-010-0389-410.1007/s00018-010-0389-4 ↗
59. 10.1016/j.tim.2004.06.00410.1016/j.tim.2004.06.004 ↗
60. 10.1111/j.1365-2958.2006.05441.x10.1111/j.1365-2958.2006.05441.x ↗
61. 10.1016/j.chom.2016.08.01010.1016/j.chom.2016.08.010 ↗
62. 10.1038/ncomms308710.1038/ncomms3087 ↗
63. 10.1016/j.molcel.2022.01.01210.1016/j.molcel.2022.01.012 ↗
64. 10.1038/s41564-020-00822-710.1038/s41564-020-00822-7 ↗
65. 10.1016/j.cell.2020.12.01710.1016/j.cell.2020.12.017 ↗
66. 10.1093/nar/gkab70410.1093/nar/gkab704 ↗
67. 10.1038/s41564-020-0691-310.1038/s41564-020-0691-3 ↗
68. 10.1093/nar/gkx61210.1093/nar/gkx612 ↗
69. 10.1016/j.celrep.2024.11448510.1016/j.celrep.2024.114485 ↗
70. 10.4161/rna.8.3.1519010.4161/rna.8.3.15190 ↗
71. 10.1128/JB.01130-1310.1128/JB.01130-13 ↗
72. 10.1093/nar/gky47510.1093/nar/gky475 ↗
73. 10.1128/MMBR.00026-1910.1128/MMBR.00026-19 ↗
74. 10.1128/AAC.02666-1610.1128/AAC.02666-16 ↗
75. 10.1128/AEM.01789-1410.1128/AEM.01789-14 ↗
76. 10.1128/IAI.69.2.885-896.200110.1128/IAI.69.2.885-896.2001 ↗
77. 10.1111/mmi.1261410.1111/mmi.12614 ↗
78. 10.1093/nar/gkv51710.1093/nar/gkv517 ↗
79. 10.1128/JB.01739-0610.1128/JB.01739-06 ↗
80. 10.1016/j.jmb.2009.10.05710.1016/j.jmb.2009.10.057 ↗
81. 10.1016/j.chom.2021.11.01410.1016/j.chom.2021.11.014 ↗
82. 10.1038/s41564-019-0634-z10.1038/s41564-019-0634-z ↗
83. 10.1128/mBio.00277-1110.1128/mBio.00277-11 ↗
84. 10.1101/pdb.prot542310.1101/pdb.prot5423 ↗
85. 10.1007/7651_2020_30710.1007/7651_2020_307 ↗