An overview of the two-component system GarR/GarS role on antibiotic production in Streptomyces coelicolor.
Streptomyces coelicolor
/ metabolism
Anti-Bacterial Agents
/ biosynthesis
Gene Expression Regulation, Bacterial
Anthraquinones
/ metabolism
Prodigiosin
/ analogs & derivatives
Transcription Factors
/ genetics
Bacterial Proteins
/ genetics
Secondary Metabolism
/ genetics
Glucose
/ metabolism
Catabolite Repression
Benzoisochromanequinones
Streptomyces
Antibiotics
Regulation
Response regulator
Sensor histidine kinase
Two-component systems
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
24 Apr 2024
24 Apr 2024
Historique:
received:
09
01
2024
accepted:
03
04
2024
revised:
23
03
2024
medline:
24
4
2024
pubmed:
24
4
2024
entrez:
24
4
2024
Statut:
epublish
Résumé
The Streptomyces genus comprises Gram-positive bacteria known to produce over two-thirds of the antibiotics used in medical practice. The biosynthesis of these secondary metabolites is highly regulated and influenced by a range of nutrients present in the growth medium. In Streptomyces coelicolor, glucose inhibits the production of actinorhodin (ACT) and undecylprodigiosin (RED) by a process known as carbon catabolite repression (CCR). However, the mechanism mediated by this carbon source still needs to be understood. It has been observed that glucose alters the transcriptomic profile of this actinobacteria, modifying different transcriptional regulators, including some of the one- and two-component systems (TCSs). Under glucose repression, the expression of one of these TCSs SCO6162/SCO6163 was negatively affected. We aimed to study the role of this TCS on secondary metabolite formation to define its influence in this general regulatory process and likely establish its relationship with other transcriptional regulators affecting antibiotic biosynthesis in the Streptomyces genus. In this work, in silico predictions suggested that this TCS can regulate the production of the secondary metabolites ACT and RED by transcriptional regulation and protein-protein interactions of the transcriptional factors (TFs) with other TCSs. These predictions were supported by experimental procedures such as deletion and complementation of the TFs and qPCR experiments. Our results suggest that in the presence of glucose, the TCS SCO6162/SCO6163, named GarR/GarS, is an important negative regulator of the ACT and RED production in S. coelicolor. KEY POINTS: • GarR/GarS is a TCS with domains for signal transduction and response regulation • GarR/GarS is an essential negative regulator of the ACT and RED production • GarR/GarS putatively interacts with and regulates activators of ACT and RED.
Identifiants
pubmed: 38656376
doi: 10.1007/s00253-024-13136-z
pii: 10.1007/s00253-024-13136-z
doi:
Substances chimiques
Anti-Bacterial Agents
0
actinorhodin
G4HH387T6Z
Anthraquinones
0
Prodigiosin
OL369FU7CJ
Transcription Factors
0
undecylprodigiosin
52340-48-4
Bacterial Proteins
0
Glucose
IY9XDZ35W2
Benzoisochromanequinones
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
306Subventions
Organisme : Consejo Nacional de Ciencia y Tecnología
ID : A1-S-9143
Informations de copyright
© 2024. The Author(s).
Références
Abriata LA, Albanesi D, Dal Peraro M, de Mendoza D (2017) Signal sensing and transduction by histidine kinases as unveiled through studies on a temperature sensor. Acc Chem Res 50(6):1359–1366. https://doi.org/10.1021/acs.accounts.6b00593
doi: 10.1021/acs.accounts.6b00593
pubmed: 28475313
Agrawal R, Sahoo BK, Saini DK (2016) Cross-talk and specificity in two-component signal transduction pathways. Future Microbiol 11(5) https://doi.org/10.2217/fmb-2016-0001
Anderssen S, Naômé A, Jadot C, Brans A, Tocquin P, Rigali S (2022) Autoregulation of transcription factors as facilitator of cis-acting element discovery. Biochim Biophys Acta - Gene Regul Mech 5:194847. https://doi.org/10.1016/j.bbagrm.2022.194847
Angell S, Lewis CG, Buttner MJ, Bibb MJ (1994) Glucose repression in Streptomyces coelicolor A3(2): a likely regulatory role for glucose kinase. Mol Gen Genet 244:135–143. https://doi.org/10.1007/bf00283514
doi: 10.1007/bf00283514
pubmed: 8052232
Arroyo-Pérez EE, González-Cerón G, Soberón-Chávez G, Georgellis D, Servín-González L (2019) A novel two-component system, encoded by the sco5282/sco5283 genes, affects Streptomyces coelicolor morphology in liquid culture. Front Microbiol 10:1568. https://doi.org/10.3389/2Ffmicb.2019.01568
doi: 10.3389/2Ffmicb.2019.01568
pubmed: 31354667
pmcid: 6629963
Bailey TL, Johnson J, Grant CE, Noble WS (2015) The MEME suite. Nucleic Acids Res 43(W1):W39–W49. https://doi.org/10.1093/2Fnar/2Fgkv416
doi: 10.1093/2Fnar/2Fgkv416
pubmed: 25953851
pmcid: 4489269
Barreiro C, Martínez-Castro M (2019) Regulation of the phosphate metabolism in Streptomyces genus: impact on the secondary metabolites. Appl Microbiol Biotechnol 103:1643–1658. https://doi.org/10.1007/s00253-018-09600-2
doi: 10.1007/s00253-018-09600-2
pubmed: 30627795
Bervoets I, Charlier D (2018) Diversity, versatility and complexity of bacterial gene regulation mechanisms: opportunities and drawbacks for applications in synthetic biology. FEMS Microbiol Rev 43(3):304–339. https://doi.org/10.1093/femsre/fuz001
doi: 10.1093/femsre/fuz001
Botas J, Rodríguez Del Río Á, Giner-Lamia J, Huerta-Cepas J (2022) GeCoViz: genomic context visualization of prokaryotic genes from a functional and evolutionary perspective. Nucleic Acids Res 50(W1):W352–W357. https://doi.org/10.1093/nar/gkac367
doi: 10.1093/nar/gkac367
pubmed: 35639770
pmcid: 9252766
Brunet YR, Habib C, Brogan AP, Artzi L, Rudner DZ (2022) Intrinsically disordered protein regions are required for cell wall homeostasis in Bacillus subtilis. Genes Dev 36(17–18):970–984. https://doi.org/10.1101/gad.349895.122
doi: 10.1101/gad.349895.122
pubmed: 36265902
pmcid: 9732909
Busche T, Winkler A, Wedderhoff I, Rückert C, Kalinowski J, Ortiz de Orué LD (2016) Deciphering the transcriptional response mediated by the redox-sensing system HbpS-SenS-SenR from streptomycetes. PLoS ONE 11(8):e0159873. https://doi.org/10.1371/journal.pone.0159873
doi: 10.1371/journal.pone.0159873
pubmed: 27541358
pmcid: 4991794
Buschiazzo A, Trajtenberg F (2019) Two-component sensing and regulation: how do histidine kinases talk with response regulators at the molecular level? Ann Rev Microbiol 73:507–528. https://doi.org/10.1146/annurev-micro-091018-05462
doi: 10.1146/annurev-micro-091018-05462
Carro L (2018) Protein-protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics. Beilstein J Org Chem 14:2881–2896. https://doi.org/10.3762/2Fbjoc.14.267
doi: 10.3762/2Fbjoc.14.267
pubmed: 30546472
pmcid: 6278769
Chandra G, Chater KF (2014) Developmental biology of Streptomyces from the perspective of 100 actinobacterial genome sequences. FEMS Microbiol Rev 38:345–379. https://doi.org/10.1111/1574-6976.12047
doi: 10.1111/1574-6976.12047
pubmed: 24164321
Chater KF (2016) Recent advances in understanding Streptomyces. F1000Research 5:2795. https://doi.org/10.12688/2Ff1000research.9534.1
doi: 10.12688/2Ff1000research.9534.1
pubmed: 27990276
pmcid: 5133688
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
doi: 10.1016/j.mib.2010.01.016
pubmed: 20223701
pmcid: 3078554
Cruz-Bautista R, Ruiz-Villafán B, Romero-Rodríguez A, Rodríguez-Sanoja R, Sánchez S (2023) Trends in the two-component system’s role in the synthesis of antibiotics by Streptomyces. Appl Microbiol Biotechnol 107:4727–4743. https://doi.org/10.1007/s00253-023-12623-z
doi: 10.1007/s00253-023-12623-z
pubmed: 37341754
pmcid: 10345050
De Castro E, Sigrist CJA, Gattiker A, Bulliard V, Langendijk-Genevaux PS, Gasteiger E, Bairoch A, Hulo N (2006) ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins. Nucleic Acids Res 34:W362-365. https://doi.org/10.1093/nar/gkl124
doi: 10.1093/nar/gkl124
pubmed: 16845026
pmcid: 1538847
Donald L, Pipite A, Subramani R, Owen J, Keyzers RA, Taufa T (2022) Streptomyces: still the biggest producer of new natural secondary metabolites, a current perspective. Microbiol Res 13(3):418–465. https://doi.org/10.3390/microbiolres13030031
doi: 10.3390/microbiolres13030031
Feeney MA, Newitt JT, Addington E, Algora-Gallardo L, Allan C, Balis L, Birke AS, Castaño-Espriu L, Charkoudian LK, Devine R, Gayrard D, Hamilton J, Hennrich O, Hoskisson PA, Keith-Baker M, Klein JG, Kruasuwan W, Mark DR, Mast Y, McHugh RE, McLean TC, Mohit E, Munnoch JT, Murray J, Noble K, Otani H, Parra J, Pereira CF, Perry L, Pintor-Escobar L, Pritchard L, Prudence SMM, Russell AH, Schniete JK, Seipke RF, Sélem-Mojica N, Undabarrena A, Vind K, van Wezel GP, Wilkinson B, Worsley SF, Duncan KR, Fernández-Martínez LT, Hutchings MI (2022) ActinoBase: tools and protocols for researchers working on Streptomyces and other filamentous actinobacteria. Microb Res 8:000824. https://doi.org/10.1099/mgen.0.000824
doi: 10.1099/mgen.0.000824
Ferrie JJ, Karr JP, Tjian R, Darzacq X (2022) “Structure”-function relationships in eukaryotic transcription factors: the role of intrinsically disordered regions in gene regulation. Mol Cell 82:3970–3984. https://doi.org/10.1016/j.molcel.2022.09.021
doi: 10.1016/j.molcel.2022.09.021
pubmed: 36265487
Fridlich R, Delalande F, Jaillard C, Lu J, Poidevin L, Cronin T, Perrocheau L, Millet-Puel G, Niepon ML, Poch O, Holmgren A, Van Dorsselaer A, Sahel JA, Léveillard T (2009) The thioredoxin-like protein rod-derived cone viability factor (RdCVFL) interacts with TAU and inhibits its phosphorylation in the retina. Mol Cell Proteomics 8(6):1206–1218. https://doi.org/10.1074/mcp.M800406-MCP200
doi: 10.1074/mcp.M800406-MCP200
pubmed: 19279044
pmcid: 2690495
Gao R, Bouillet S, Stock AM (2019) Structural basis of response regulator function. Ann Rev Microbiol 73:175–197. https://doi.org/10.1146/annurev-micro-020518-115931
doi: 10.1146/annurev-micro-020518-115931
Gubbens J, Janus M, Florea BI, Overkleeft HS, Van Wezel GP (2012) Identification of glucose kinase-dependent and -independent pathways for carbon control of primary metabolism, development and antibiotic production in Streptomyces coelicolor by quantitative proteomics. Mol Microbiol 86:1490–1507. https://doi.org/10.1111/mmi.12072
doi: 10.1111/mmi.12072
pubmed: 23078239
Gust B, Challis GL, Fowler K, Kieser T, Chater KF (2003) PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. Proc Natl Acad Sci USA 100(4):1541–1546. https://doi.org/10.1073/pnas.0337542100
doi: 10.1073/pnas.0337542100
pubmed: 12563033
pmcid: 149868
Guzmán S, Ramos I, Moreno E, Ruiz B, Rodríguez-Sanoja R, Escalante L, Langley E, Sánchez S (2005) Sugar uptake and sensitivity to carbon catabolite repression in Streptomyces peucetius var. caesius. Appl Microbiol Biotechnol 69:200–206. https://doi.org/10.1007/s00253-005-1965-7
doi: 10.1007/s00253-005-1965-7
pubmed: 15812641
Hallgren J, Tsirigos KD, Pedersen MD, Almagro AJJ, Marcatili P, Nielsen H, Krogh A, Winther O (2022) DeepTMHMM predicts alpha and beta transmembrane proteins using deep neural networks. bioRxiv 487609. https://doi.org/10.1101/2022.04.08.487609
Hanes R, Zhang F, Huang Z (2023) Protein interaction network analysis to investigate stress response, virulence, and antibiotic resistance mechanisms in Listeria monocytogenes. Microorganisms 11(4):930. https://doi.org/10.3390/microorganisms11040930
doi: 10.3390/microorganisms11040930
pubmed: 37110353
pmcid: 10144942
Huang J, Lih CJ, Pan KH, Cohen SN (2001) Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways in Streptomyces coelicolor using DNA microarrays. Genes Dev 15(23):3183–3192. https://doi.org/10.1101/2Fgad.943401
doi: 10.1101/2Fgad.943401
pubmed: 11731481
pmcid: 312833
Jacob-Dubuisson F, Mechaly A, Betton JM, Antoine R (2018) Structural insights into the signaling mechanisms of two-component systems. Sci Signal 16:585–593. https://doi.org/10.1126/scisignal.aaz2970
doi: 10.1126/scisignal.aaz2970
Jin S, Hui M, Lu Y, Zhao Y (2023) An overview on the two-component systems of Streptomyces coelicolor. World J Microbiol Biotechnol 39:78. https://doi.org/10.1007/s11274-023-03522-6
doi: 10.1007/s11274-023-03522-6
pubmed: 36645528
Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, Tunyasuvunakool K, Bates R, Žídek A, Potapenko A, Bridgland A, Meyer C, Kohl SAA, Ballard AJ, Cowie A, Romera-Paredes B, Nikolov S, Jain R, Adler J, Back T, Petersen S, Reiman D, Clancy E, Zielinski M, Steinegger M, Pacholska M, Berghammer T, Bodenstein S, Silver D, Vinyals O, Senior AW, Kavukcuoglu K, Kohli P, Hassabis D (2021) Highly accurate protein structure prediction with AlphaFold. Nature 596:583–589. https://doi.org/10.1038/s41586-021-03819-2
doi: 10.1038/s41586-021-03819-2
pubmed: 34265844
pmcid: 8371605
Kieser T, Hopwood DA, Bibb JM, Chater KF, Buttner MJ (2000) Practical Streptomyces Genetics. John Innes Foundation. Norwich
Krysenko S (2023) Impact of nitrogen-containing compounds on secondary metabolism in Streptomyces spp. A source of metabolic engineering strategies. SynBio 1(3):204–225. https://doi.org/10.3390/synbio1030015
doi: 10.3390/synbio1030015
Liu G, Chater KF, Chandra G, Niu G, Tan H (2013) Molecular regulation of antibiotic biosynthesis in Streptomyces. Microbiol Mol Biol Rev 77(1):112–143. https://doi.org/10.1128/mmbr.00054-12
doi: 10.1128/mmbr.00054-12
pubmed: 23471619
pmcid: 3591988
Liu L, Cheng Y, Lyu M, Zhao X, Wen Y, Li J, Chen Z (2019) AveI, an AtrA homolog of Streptomyces avermitilis, controls avermectin and oligomycin production, melanogenesis, and morphological differentiation. Appl Microbiol Biotechnol 103(20):8459–8472. https://doi.org/10.1007/s00253-019-10062-3
doi: 10.1007/s00253-019-10062-3
pubmed: 31422450
Magdalena Ś, Tenconi E, Rigali S, Van Wezel GP (2012) Functional analysis of the N-acetylglucosamine metabolic genes of Streptomyces coelicolor and role in control of development and antibiotic production. J Bacteriol 194:1136–1144. https://doi.org/10.1128/2FJB.06370-11
doi: 10.1128/2FJB.06370-11
McGuffin LJ, Edmunds NS, Genc AG, Alharbi SMA, Salehe BR, Adiyaman R (2023) Prediction of protein structures, functions and interactions using the IntFOLD7, MultiFOLD and ModFOLDdock servers. Nucleic Acids Res 51(W1):W274–W280. https://doi.org/10.1093/nar/gkad297
doi: 10.1093/nar/gkad297
pubmed: 37102670
pmcid: 10320135
Oren A, Garrity GM (2021) Valid publication of the names of forty-two phyla of prokaryotes. Int J Syst Evol Microbiol 71(10). https://doi.org/10.1099/ijsem.0.005056
Paysan-Lafosse T, Blum M, Chuguransky S, Grego T, Pinto BL, Salazar GA, Bileschi ML, Bork P, Bridge A, Colwell L, Gough J, Haft DH, Letunić I, Marchler-Bauer A, Mi H, Natale DA, Orengo CA, Pandurangan AP, Rivoire C, Sigrist CJA, Sillitoe I, Thanki N, Thomas PD, Tosatto SCE, Wu CH, Bateman A (2022) InterPro in 2022. Nucleic Acids Res 51(D1):D418–D427. https://doi.org/10.1093/nar/gkac993
doi: 10.1093/nar/gkac993
pmcid: 9825450
Pettersen EF, Goddard TD, Huang CC, Meng EC, Couch GS, Croll TI, Morris JH, Ferrin TE (2021) UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci 30:70–82. https://doi.org/10.1002/pro.3943
doi: 10.1002/pro.3943
pubmed: 32881101
Rocha-Mendoza D, Manzo-Ruiz M, Romero-Rodríguez A, Ruiz-Villafán B, Rodríguez-Sanoja R, Sánchez S (2021) Dissecting the role of the two Streptomyces peucetius var. caesius glucokinases in the sensitivity to carbon catabolite repression. J Ind Microbiol Biotechnol 48(9–10):kuab047. https://doi.org/10.1093/jimb/kuab047
doi: 10.1093/jimb/kuab047
Romero-Rodríguez A, Robledo-Casados I, Sánchez S (2015) An overview on transcriptional regulators in Streptomyces. Biochim Biophys Acta 1849:1017–1039. https://doi.org/10.1016/j.bbagrm.2015.06.007
doi: 10.1016/j.bbagrm.2015.06.007
pubmed: 26093238
Romero-Rodríguez A, Ruiz-Villafán B, Tierrafría VH, Rodríguez-Sanoja R, Sánchez S (2016a) Carbon catabolite regulation of secondary metabolite formation and morphological differentiation in Streptomyces coelicolor. Appl Biochem Biotechnol 180:1152–1166. https://doi.org/10.1007/s12010-016-2158-9
doi: 10.1007/s12010-016-2158-9
pubmed: 27372741
Romero-Rodríguez A, Rocha D, Ruiz-Villafán B, Tierrafría V, Rodríguez-Sanoja R, Segura-González D, Sánchez S (2016b) Transcriptomic analysis of a classical model of carbon catabolite regulation in Streptomyces coelicolor. BMC Microbiol 16:1–16. https://doi.org/10.1186/s12866-016-0690-y
doi: 10.1186/s12866-016-0690-y
Romero-Rodríguez A, Maldonado-Carmona N, Ruiz-Villafán B, Koirala N, Rocha D, Sánchez S (2018) Interplay between carbon, nitrogen and phosphate utilization in the control of secondary metabolite production in Streptomyces. Anton Leeuw Int J Gen Mol Microbiol 111:761–781. https://doi.org/10.1007/s10482-018-1073-1
doi: 10.1007/s10482-018-1073-1
Rozas D, Gullón S, Mellado RP (2012) A novel two-component system involved in the transition to secondary metabolism in Streptomyces coelicolor. PLoS ONE 7(2):e31760. https://doi.org/10.1371/journal.pone.0031760
doi: 10.1371/journal.pone.0031760
pubmed: 22347508
pmcid: 3276577
Rudd BAM, Hopwood DA (1980) A pigmented mycelial antibiotic in Streptomyces coelicolor: control by a chromosomal gene cluster. J Gen Microbiol 119:333–340. https://doi.org/10.1099/00221287-119-2-333
doi: 10.1099/00221287-119-2-333
pubmed: 7229612
Ruiz-Villafán B, Cruz-Bautista R, Manzo-Ruiz M, Passari AK, Villarreal-Gómez K, Rodríguez-Sanoja R, Sánchez S (2021) Carbon catabolite regulation of secondary metabolite formation, an old but not well-established regulatory system. Microb Biotechnol 0:1–15. https://doi.org/10.1111/1751-7915.13791
Sánchez de la Nieta R, Santamaría RI, Díaz M (2022) Two-component systems of Streptomyces coelicolor: an intricate network to be unraveled. Int J Mol Sci 23(23):15085. https://doi.org/10.3390/ijms232315085
doi: 10.3390/ijms232315085
pubmed: 36499414
pmcid: 9739842
Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, Annika GL, Fang T, Doncheva NT, Pyysalo S, Bork P, Jensen LJ, von Mering C (2023) The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 51(D1):D638-646. https://doi.org/10.1093/nar/gkac1000
doi: 10.1093/nar/gkac1000
pubmed: 36370105
Taboada B, EstradaK CR, Merino E (2018) Operon-mapper: a web server for precise operon identification in bacterial and archaeal genomes. Bioinf 34:4118–4120. https://doi.org/10.1093/bioinformatics/bty496
doi: 10.1093/bioinformatics/bty496
Thakur P, Gauba P (2024) Expression analysis of nitrogen metabolism genes in Lelliottia amnigena PTJIIT1005, comparison with Escherichia coli K12 and validation of nitrogen metabolism genes. Biochem Genet. https://doi.org/10.1007/s10528-024-10677-w
doi: 10.1007/s10528-024-10677-w
pubmed: 38341394
Tierrafría V, Licona-Cassani C, Maldonado-Carmona N, Romero-Rodríguez A, Centeno-Leija S, Marcellin E, Rodríguez-Sanoja R, Ruiz B, Nielsen L, Sánchez S (2016) Deletion of the hypothetical protein SCO2127 of Streptomyces coelicolor allowed identification of a new regulator of actinorhodin production. Appl Microbiol Biotechnol 100(21):9229–9237. https://doi.org/10.1007/s00253-016-7811-2
doi: 10.1007/s00253-016-7811-2
pubmed: 27604626
Uguru GC, Stephens KE, Stead JA, Towle JE, Baumberg S, McDowall KJ (2005) Transcriptional activation of the pathway-specific regulator of the actinorhodin biosynthetic genes in Streptomyces coelicolor. Mol Microbiol 58(1):131–150. https://doi.org/10.1111/j.1365-2958.2005.04817.x
doi: 10.1111/j.1365-2958.2005.04817.x
pubmed: 16164554
van der Heul HU, Bilyk BL, McDowall KJ, Seipke RF, van Wezel GP (2018) Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era. Nat Prod Rep 35(6):575–604. https://doi.org/10.1039/c8np00012c
doi: 10.1039/c8np00012c
pubmed: 29721572
Wright LF, Hopwood DA (1976) Actinorhodin is a chromosomally determined antibiotic in Streptomyces coelicolorA3(2). J Gen Microbiol 96:289–329. https://doi.org/10.1099/00221287-96-2-289
doi: 10.1099/00221287-96-2-289
pubmed: 993778
Wu W, Kang Y, Hou B, Ye J, Wang R, Wu H, Zhang H (2023) Characterization of a TetR-type positive regulator AtrA for lincomycin production in Streptomyces lincolnensis. Biosci Biotechnol Biochem 87:786–795. https://doi.org/10.1093/bbb/zbad046
doi: 10.1093/bbb/zbad046
pubmed: 37076767
Yan Z, Xia L, Xu X, Ma B, Yuan X, Yang K, Li K, Ye X, Zhang L, Chen T (2023) Exploring calcium channel blocker as a candidate drug for Pseudomonas aeruginosa through network pharmacology and experimental validation. Chem Biol Drug Des 102(6):1353–1366. https://doi.org/10.1111/cbdd.14322
doi: 10.1111/cbdd.14322
pubmed: 37599112
Zhang N, Dong Y, Zhou H, Cui H (2022) Effect of PAS-LuxR family regulators on the secondary metabolism of Streptomyces. Antibiotics (Basel) 11:1783. https://doi.org/10.3389/2Ffmicb.2019.01568
doi: 10.3389/2Ffmicb.2019.01568
pubmed: 36551440