Abstract
Bacteria would adapt to ever-changing multifaceted environments. Two-component systems (TCSs) are predominantly used by bacteria to respond to environmental cues. TCSs regulate the expression of genes involved in quorum sensing, biofilm formation, cell growth and division, acid tolerance, spore formation, virulence, drug resistance, and nitrogen fixation. TCSs are composed of sensor (histidine kinase; HK—membrane-bound homodimeric protein) and a cognate response regulator (RR) which on phosphorylation by HK is converted into active DNA binding form and alters gene expression. TCSs are used by virulent bacteria to control the expression of virulence factors. The aerobic respiration control (Arc) TCS plays a role in anaerobic to aerobic shift by sensing oxygen availability or consumption. Evolutionary dynamics explains a dramatic increase in the number of TCSs within many bacterial genomes through gene duplication and the subsequent divergence, enabling the microbes to sense and respond to various environmental stimuli. Bacterial TCSs are promising targets for antimicrobial therapy.
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Further Reading
Agrawal R, Sahoo BK, Saini DK (2016) Cross-talk and specificity in two-component signal transduction pathways. Future Microbiol 11:685–697. https://doi.org/10.2217/fmb-2016-0001
Alexeeva S, Hellingwerf KJ, Teixeira de Mattos MJ (2003) Requirement of ArcA for redox regulation in Escherichia coli under microaerobic but not anaerobic or aerobic conditions. J Bacteriol 185(1):204–209. https://doi.org/10.1128/JB.185.1.204-209.2003
Barakat M, Ortet P, Whitworth DE (2011) P2CS: a database of prokaryotic two-component systems. Nucleic Acids Res 39(Database issue):D771–D776. https://doi.org/10.1093/nar/gkq1023
Barrett JF, Goldschmidt RM, Lawrence LE, Foleno B, Chen R, Demers JP, Johnson S, Kanojia R, Fernandez J, Bernstein J, Licata L, Donetz A, Huang S, Hlasta DJ, Macielag MJ, Ohemeng K, Frechette R, Frosco MB, Klaubert DH, Whiteley JM et al (1998) Antibacterial agents that inhibit two-component signal transduction systems. Proc Natl Acad Sci USA 95(9):5317–5322. https://doi.org/10.1073/pnas.95.9.5317
Beier D, Gross R (2006) Regulation of bacterial virulence by two-component systems. Curr Opin Microbiol 9(2):143–152. https://doi.org/10.1016/j.mib.2006.01.005
Bijlsma JJ, Groisman EA (2003) Making informed decisions: regulatory interactions between two-component systems. Trends Microbiol 11(8):359–366
Bourret RB, Silversmith RE (2010) Two-component signal transduction. Curr Opin Microbiol 13(2):113–115. https://doi.org/10.1016/j.mib.2010.02.003
Bretl DJ, Demetriadou C, Zahrt TC (2011) Adaptation to environmental stimuli within the host: two-component signal transduction systems of Mycobacterium tuberculosis. Microbiol Mol Biol Rev 75(4):566–582. https://doi.org/10.1128/MMBR.05004-11
Brown AN, Anderson MT, Bachman MA, Mobley HLT (2022) The ArcAB two-component system: function in metabolism, redox control, and infection. Microbiol Mol Biol Rev 86(2):e0011021. https://doi.org/10.1128/mmbr.00110-21
Caliskan M, Poschmann G, Gudzuhn M, Waldera-Lupa D, Molitor R, Strunk CH, Streit WR, Jaeger KE, Stühler K, Kovacic F (2023) Pseudomonas aeruginosa responds to altered membrane phospholipid composition by adjusting the production of two-component systems, proteases and iron uptake proteins. Biochim Biophys Acta Mol Cell Biol Lipids 1868(6):159317. https://doi.org/10.1016/j.bbalip.2023.159317
Cheung J, Hendrickson WA (2010) Sensor domains of two-component regulatory systems. Curr Opin Microbiol 13(2):116–123. https://doi.org/10.1016/j.mib.2010.01.016
Crépin S, Chekabab SM, Le Bihan G, Bertrand N, Dozois CM, Harel J (2011) The Pho regulon and the pathogenesis of Escherichia coli. Vet Microbiol 153(1–2):82–88. https://doi.org/10.1016/j.vetmic.2011.05.043
Desai SK, Kenney LJ (2017) To ∼P or not to ∼P? Non-canonical activation by two-component response regulators. Mol Microbiol 103(2):203–213. https://doi.org/10.1111/mmi.13532
Dhaked HPS, Biswas I (2022) Distribution of two-component signal transduction systems BlpRH and ComDE across streptococcal species. Front Microbiol 13:960994. https://doi.org/10.3389/fmicb.2022.960994
Edwards AN, McBride SM (2023) The RgaS-RgaR two-component system promotes Clostridioides difficile sporulation through a small RNA and the Agr1 system. bioRxiv. https://doi.org/10.1101/2023.06.26.546640
Gao R, Stock AM (2009) Biological insights from structures of two-component proteins. Ann Rev Microbiol 63:133–154. https://doi.org/10.1146/annurev.micro.091208.073214
Gómez-Mejia A, Gámez G, Hammerschmidt S (2018) Streptococcus pneumoniae two-component regulatory systems: the interplay of the pneumococcus with its environment. Int J Med Microbiol 308(6):722–737. https://doi.org/10.1016/j.ijmm.2017.11.012
Gotoh Y, Eguchi Y, Watanabe T, Okamoto S, Doi A, Utsumi R (2010) Two-component signal transduction as potential drug targets in pathogenic bacteria. Curr Opin Microbiol 13(2):232–239. https://doi.org/10.1016/j.mib.2010.01.008
Groisman EA (2016) Feedback control of two-component regulatory systems. Ann Rev Microbiol 70:103–124. https://doi.org/10.1146/annurev-micro-102215-095331
Gumerov VM, Ulrich LE, Zhulin IB (2024) MiST 4.0: a new release of the microbial signal transduction database, now with a metagenomic component. Nucleic Acids Res D1:D647–D653
He LY, Le YJ, Guo Z, Li S, Yang XY (2021) The role and regulatory network of the CiaRH two-component system in streptococcal species. Front Microbiol 12:693858. https://doi.org/10.3389/fmicb.2021.693858
Hoch JA (2000) Two-component and phosphorelay signal transduction. Curr Opin Microbiol 3(2):165–170. https://doi.org/10.1016/s1369-5274(00)00070-9
Iuchi S, Weiner L (1996) Cellular and molecular physiology of Escherichia coli in the adaptation to aerobic environments. J Biochem 120(6):1055–1063. https://doi.org/10.1093/oxfordjournals.jbchem.a021519
Jacob-Dubuisson F, Mechaly A, Betton JM, Antoine R (2018) Structural insights into the signalling mechanisms of two-component systems. Nat Rev Microbiol 16(10):585–593. https://doi.org/10.1038/s41579-018-0055-7
Lange R, Wagner C, de Saizieu A, Flint N, Molnos J, Stieger M, Caspers P, Kamber M, Keck W, Amrein KE (1999) Domain organization and molecular characterization of 13 two-component systems identified by genome sequencing of Streptococcus pneumoniae. Gene 237(1):223–234. https://doi.org/10.1016/s0378-1119(99)00266-8
Loui C, Chang AC, Lu S (2009) Role of the ArcAB two-component system in the resistance of Escherichia coli to reactive oxygen stress. BMC Microbiol 9:183. https://doi.org/10.1186/1471-2180-9-183
Ma P, Phillips-Jones MK (2021) Membrane sensor histidine kinases: insights from structural, ligand and inhibitor studies of full-length proteins and signalling domains for antibiotic discovery. Molecules (Basel, Switzerland) 26(16):5110. https://doi.org/10.3390/molecules26165110
Pasqua M, Coluccia M, Eguchi Y, Okajima T, Grossi M, Prosseda G, Utsumi R, Colonna B (2022) Roles of two-component signal transduction systems in shigella virulence. Biomol Ther 12(9):1321. https://doi.org/10.3390/biom12091321
Perron K, Caille O, Rossier C, Van Delden C, Dumas JL, Köhler T (2004) CzcR-CzcS, a two-component system involved in heavy metal and carbapenem resistance in Pseudomonas aeruginosa. J Biol Chem 279(10):8761–8768. https://doi.org/10.1074/jbc.M312080200
Rajput A, Seif Y, Choudhary KS, Dalldorf C, Poudel S, Monk JM, Palsson BO (2021) Pangenome analytics reveal two-component systems as conserved targets in ESKAPEE pathogens. mSystems 6(1):e00981–e00920. https://doi.org/10.1128/mSystems.00981-20
Robinson VL, Buckler DR, Stock AM (2000) A tale of two components: a novel kinase and a regulatory switch. Nat Struct Biol 7(8):626–633. https://doi.org/10.1038/77915
Salazar ME, Laub MT (2015) Temporal and evolutionary dynamics of two-component signaling pathways. Curr Opin Microbiol 24:7–14
Scharf BE (2010) Summary of useful methods for two-component system research. Curr Opin Microbiol 13(2):246–252. https://doi.org/10.1016/j.mib.2010.01.006
Stephenson K, Hoch JA (2002a) Virulence- and antibiotic resistance-associated two-component signal transduction systems of Gram-positive pathogenic bacteria as targets for antimicrobial therapy. Pharmacol Ther 93(2–3):293–305. https://doi.org/10.1016/s0163-7258(02)00198-5
Stephenson K, Hoch JA (2002b) Two-component and phosphorelay signal-transduction systems as therapeutic targets. Curr Opin Pharmacol 2(5):507–512. https://doi.org/10.1016/s1471-4892(02)00194-7
Stock AM, Robinson VL, Goudreau PN (2000a) Two-component signal transduction. Annu Rev Biochem 69:183–215
Stock AM, Robinson VL, Goudreau PN (2000b) Two-component signal transduction. Annu Rev Biochem 69:183–215. https://doi.org/10.1146/annurev.biochem.69.1.183
Sultan M, Arya R, Kim KK (2021) Roles of two-component systems in Pseudomonas aeruginosa virulence. Int J Mol Sci 22(22):12152. https://doi.org/10.3390/ijms222212152
Tiwari S, Jamal SB, Hassan SS, Carvalho PVSD, Almeida S, Barh D, Ghosh P, Silva A, Castro TLP, Azevedo V (2017) Two-component signal transduction systems of pathogenic bacteria as targets for antimicrobial therapy: an overview. Front Microbiol 8:1878. https://doi.org/10.3389/fmicb.2017.01878
Tobe T (2008) The roles of two-component systems in virulence of pathogenic Escherichia coli and Shigella spp. Adv Exp Med Biol 631:189–199. https://doi.org/10.1007/978-0-387-78885-2_13
Zhu Y, Dou Q, Du L, Wang Y (2023) QseB/QseC: a two-component system globally regulating bacterial behaviors. Trends Microbiol 31(7):749–762. https://doi.org/10.1016/j.tim.2023.02.001
Zschiedrich CP, Keidel V, Szurmant H (2016) Molecular mechanisms of two-component signal transduction. J Mol Biol 428(19):3752–3775. https://doi.org/10.1016/j.jmb.2016.08.003
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Jagtap, S. (2024). Two-Component Regulatory Systems in Microbial Pathogenesis. In: Verma, P. (eds) Industrial Microbiology and Biotechnology. Springer, Singapore. https://doi.org/10.1007/978-981-97-1912-9_13
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