SOS Response: Activation, Impact, and Drug Targets

Overview

Journal mLife

Date 2024 Oct 3

PMID 39359682

Authors

Kaiying Cheng

Yukang Sun

Huan Yu

Yingxuan Hu

Yini He

Yuanyuan Shen

Affiliations

Soon will be listed here.

Abstract

is a common cause of diverse infections, ranging from superficial to invasive, affecting both humans and animals. The widespread use of antibiotics in clinical treatments has led to the emergence of antibiotic-resistant strains and small colony variants. This surge presents a significant challenge in eliminating infections and undermines the efficacy of available treatments. The bacterial Save Our Souls (SOS) response, triggered by genotoxic stressors, encompasses host immune defenses and antibiotics, playing a crucial role in bacterial survival, invasiveness, virulence, and drug resistance. Accumulating evidence underscores the pivotal role of the SOS response system in the pathogenicity of . Inhibiting this system offers a promising approach for effective bactericidal treatments and curbing the evolution of antimicrobial resistance. Here, we provide a comprehensive review of the activation, impact, and key proteins associated with the SOS response in . Additionally, perspectives on therapeutic strategies targeting the SOS response for , both individually and in combination with traditional antibiotics are proposed.

References

Lee A, Ross C, Zeng B, Singleton S . A molecular target for suppression of the evolution of antibiotic resistance: inhibition of the Escherichia coli RecA protein by N(6)-(1-naphthyl)-ADP. J Med Chem. 2005; 48(17):5408-11. DOI: 10.1021/jm050113z. View

Voter A, Killoran M, Ananiev G, Wildman S, Hoffmann F, Keck J . A High-Throughput Screening Strategy to Identify Inhibitors of SSB Protein-Protein Interactions in an Academic Screening Facility. SLAS Discov. 2017; 23(1):94-101. PMC: 5667550. DOI: 10.1177/2472555217712001. View

Arias C, Murray B . Antibiotic-resistant bugs in the 21st century--a clinical super-challenge. N Engl J Med. 2009; 360(5):439-43. DOI: 10.1056/NEJMp0804651. View

Kohanski M, Dwyer D, Collins J . How antibiotics kill bacteria: from targets to networks. Nat Rev Microbiol. 2010; 8(6):423-35. PMC: 2896384. DOI: 10.1038/nrmicro2333. View

Selva L, Viana D, Regev-Yochay G, Trzcinski K, Corpa J, Lasa I . Killing niche competitors by remote-control bacteriophage induction. Proc Natl Acad Sci U S A. 2009; 106(4):1234-8. PMC: 2633583. DOI: 10.1073/pnas.0809600106. View

Ubeda C, Maiques E, Tormo M, Campoy S, Lasa I, Barbe J . SaPI operon I is required for SaPI packaging and is controlled by LexA. Mol Microbiol. 2007; 65(1):41-50. DOI: 10.1111/j.1365-2958.2007.05758.x. View

Kohanski M, Dwyer D, Hayete B, Lawrence C, Collins J . A common mechanism of cellular death induced by bactericidal antibiotics. Cell. 2007; 130(5):797-810. DOI: 10.1016/j.cell.2007.06.049. View

Janion C . Inducible SOS response system of DNA repair and mutagenesis in Escherichia coli. Int J Biol Sci. 2008; 4(6):338-44. PMC: 2556049. DOI: 10.7150/ijbs.4.338. View

Sirois S, Szatmari G . Detection of XerC and XerD recombinases in gram-negative bacteria of the family Enterobacteriaceae. J Bacteriol. 1995; 177(14):4183-6. PMC: 177159. DOI: 10.1128/jb.177.14.4183-4186.1995. View

10.

Chen J, Novick R . Phage-mediated intergeneric transfer of toxin genes. Science. 2009; 323(5910):139-41. DOI: 10.1126/science.1164783. View

11.

Michel B, Sinha A, Leach D . Replication Fork Breakage and Restart in Escherichia coli. Microbiol Mol Biol Rev. 2018; 82(3). PMC: 6094043. DOI: 10.1128/MMBR.00013-18. View

12.

Yang J, Sun Y, Wang Y, Hao W, Cheng K . Structural and DNA end resection study of the bacterial NurA-HerA complex. BMC Biol. 2023; 21(1):42. PMC: 9960219. DOI: 10.1186/s12915-023-01542-0. View

13.

Gottschalk S, Ifrah D, Lerche S, Gottlieb C, Cohn M, Hiasa H . The antimicrobial lysine-peptoid hybrid LP5 inhibits DNA replication and induces the SOS response in Staphylococcus aureus. BMC Microbiol. 2013; 13:192. PMC: 3751284. DOI: 10.1186/1471-2180-13-192. View

14.

Lin E, Huang C . Crystal structure of the single-stranded DNA-binding protein SsbB in complex with the anticancer drug 5-fluorouracil: Extension of the 5-fluorouracil interactome to include the oligonucleotide/oligosaccharide-binding fold protein. Biochem Biophys Res Commun. 2020; 534:41-46. DOI: 10.1016/j.bbrc.2020.11.125. View

15.

Liu L, Ingmer H, Vestergaard M . Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in . Antibiotics (Basel). 2021; 10(1). PMC: 7829806. DOI: 10.3390/antibiotics10010082. View

16.

Frees D, Gerth U, Ingmer H . Clp chaperones and proteases are central in stress survival, virulence and antibiotic resistance of Staphylococcus aureus. Int J Med Microbiol. 2014; 304(2):142-9. DOI: 10.1016/j.ijmm.2013.11.009. View

17.

Mo C, Culyba M, Selwood T, Kubiak J, Hostetler Z, Jurewicz A . Inhibitors of LexA Autoproteolysis and the Bacterial SOS Response Discovered by an Academic-Industry Partnership. ACS Infect Dis. 2017; 4(3):349-359. PMC: 5893282. DOI: 10.1021/acsinfecdis.7b00122. View

18.

Thabet M, Penades J, Haag A . The ClpX protease is essential for inactivating the CI master repressor and completing prophage induction in Staphylococcus aureus. Nat Commun. 2023; 14(1):6599. PMC: 10584840. DOI: 10.1038/s41467-023-42413-0. View

19.

Huang Y, Huang C . SAAV2152 is a single-stranded DNA binding protein: the third SSB in . Oncotarget. 2018; 9(29):20239-20254. PMC: 5945547. DOI: 10.18632/oncotarget.24427. View

20.

Uhlemann A, Otto M, Lowy F, DeLeo F . Evolution of community- and healthcare-associated methicillin-resistant Staphylococcus aureus. Infect Genet Evol. 2013; 21:563-74. PMC: 3884050. DOI: 10.1016/j.meegid.2013.04.030. View