AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Genes & Diseases Article
PDF (4.5 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Review Article | Open Access

The transcriptional regulators of virulence for Pseudomonas aeruginosa: Therapeutic opportunity and preventive potential of its clinical infections

Xiaolong Shaoa,b,( ), Chunyan Yaob, Yiqing Dingb, Haiyan Huc, Guoliang Qiana, Mingliang Heb, Xin Dengb,d,e( )
College of Plant Protection, Laboratory of Plant Immunity, Key Laboratory of Integrated Management of Crop Diseases and Pests, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China
Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China
School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou, Guangdong 510006, China
Tung Biomedical Sciences Centre, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China
Shenzhen Research Institute, City University of Hong Kong, Shenzhen, Guangdong 518057, China

Peer review under responsibility of Chongqing Medical University.

Show Author Information

Abstract

In Pseudomonas aeruginosa (P. aeruginosa), transcription factors (TFs) are important mediators in the genetic regulation of adaptability and pathogenicity to respond to multiple environmental stresses and host defences. The P. aeruginosa genome harbours 371 putative TFs; of these, about 70 have been shown to regulate virulence-associated phenotypes by binding to the promoters of their target genes. Over the past three decades, several techniques have been applied to identify TF binding sites on the P. aeruginosa genome, and an atlas of TF binding patterns has been mapped. The virulence-associated regulons of TFs show complex crosstalk in P. aeruginosa’s regulatory network. In this review, we summarise the recent literature on TF regulatory networks involved in the quorum-sensing system, biofilm formation, pyocyanin synthesis, motility, the type Ⅲ secretion system, the type Ⅵ secretion system, and oxidative stress responses. We discuss future perspectives that could provide insights and targets for preventing clinical infections caused by P. aeruginosa based on the global regulatory network of transcriptional regulators.

Keywords

CrosstalkPseudomonas aeruginosaVirulenceRegulatory networkTranscriptional regulators

References

1

Deretic V, Schurr MJ, Yu H. Pseudomonas aeruginosa, mucoidy and the chronic infection phenotype in cystic fibrosis. Trends Microbiol. 1995;3(9):351-356.
Crossref Google Scholar
2

Impey RE, Panjikar S, Hall CJ, et al. Identification of two dihydrodipicolinate synthase isoforms from Pseudomonas aeruginosa that differ in allosteric regulation. FEBS J. 2020;287(2):386-400.
Crossref Google Scholar
3

Kostylev M, Kim DY, Smalley NE, Salukhe I, Greenberg EP, Dandekar AA. Evolution of the Pseudomonas aeruginosa quorum-sensing hierarchy. Proc Natl Acad Sci U S A. 2019;116(14):7027-7032.
Crossref Google Scholar
4

Liu Y, Ling L, Wong SH, et al. Outcomes of respiratory viral-bacterial co-infection in adult hospitalized patients. EClinicalMedicine. 2021;37:100955.
Crossref Google Scholar
5

Qu J, Cai Z, Liu Y, et al. Persistent bacterial coinfection of a COVID-19 patient caused by a genetically adapted Pseudomonas aeruginosa chronic colonizer. Front Cell Infect Microbiol. 2021;11:641920.
Crossref Google Scholar
6

Goodman AL, Kulasekara B, Rietsch A, Boyd D, Smith RS, Lory S. A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa. Dev Cell. 2004;7(5):745-754.
Crossref Google Scholar
7

Hauser AR. The type Ⅲ secretion system of Pseudomonas aeruginosa: infection by injection. Nat Rev Microbiol. 2009;7(9):654-665.
Crossref Google Scholar
8

Hogardt M, Heesemann J. Microevolution of Pseudomonas aeruginosa to a chronic pathogen of the cystic fibrosis lung. Curr Top Microbiol Immunol. 2013;358:91-118.
Crossref Google Scholar
9

Olejnickova K, Hola V, Ruzicka F. Catheter-related infections caused by Pseudomonas aeruginosa: virulence factors involved and their relationships. Pathog Dis. 2014;72(2):87-94.
Crossref Google Scholar
10

Schuster M, Greenberg EP. A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa. Int J Med Microbiol. 2006;296(2-3):73-81.
Crossref Google Scholar
11

Smith RS, Iglewski BH. P. Aeruginosa quorum-sensing systems and virulence. Curr Opin Microbiol. 2003;6(1):56-60.
Crossref Google Scholar
12

Jimenez PN, Koch G, Thompson JA, Xavier KB, Cool RH, Quax WJ. The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol Mol Biol Rev. 2012;76(1):46-65.
Crossref Google Scholar
13

Chastre J, Wunderink R, Prokocimer P, Lee M, Kaniga K, Friedland I. Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. Crit Care Med. 2008;36(4):1089-1096.
Crossref Google Scholar
14

Luyt CE, Aubry A, Lu Q, et al. Imipenem, meropenem, or doripenem to treat patients with Pseudomonas aeruginosa ventilator-associated pneumonia. Antimicrob Agents Chemother. 2014;58(3):1372-1380.
Crossref Google Scholar
15

Walkty A, Adam H, Baxter M, et al. In vitro activity of plazomicin against 5,015 gram-negative and gram-positive clinical isolates obtained from patients in canadian hospitals as part of the CANWARD study, 2011-2012. Antimicrob Agents Chemother. 2014;58(5):2554-2563.
Crossref Google Scholar
16

Pankuch GA, Lin G, Kubo A, Armstrong ES, Appelbaum PC, Kosowska-Shick K. Activity of ACHN-490 tested alone and in combination with other agents against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2011;55(5):2463-2465.
Crossref Google Scholar
17

Cigana C, Bernardini F, Facchini M, et al. Efficacy of the novel antibiotic POL7001 in preclinical models of Pseudomonas aeruginosa pneumonia. Antimicrob Agents Chemother. 2016;60(8):4991-5000.
Crossref Google Scholar
18

Shao X, Xie Y, Zhang Y, et al. Novel therapeutic strategies for treating Pseudomonas aeruginosa infection. Expet Opin Drug Discov. 2020;15(12):1403-1423.
Crossref Google Scholar
19

Winsor GL, Griffiths EJ, Lo R, Dhillon BK, Shay JA, Brinkman FS. Enhanced annotations and features for comparing thousands of Pseudomonas genomes in the Pseudomonas genome database. Nucleic Acids Res. 2016;44(D1):D646-D653.
Crossref Google Scholar
20

Gilbert KB, Kim TH, Gupta R, Greenberg EP, Schuster M. Global position analysis of the Pseudomonas aeruginosa quorum-sensing transcription factor LasR. Mol Microbiol. 2009;73(6):1072-1085.
Crossref Google Scholar
21

Bartlett A, O’Malley RC, Huang SC, et al. Mapping genome-wide transcription-factor binding sites using DAP-seq. Nat Protoc. 2017;12(8):1659-1672.
Crossref Google Scholar
22

Trouillon J, Imbert L, Villard AM, Vernet T, Attrée I, Elsen S. Determination of the two-component systems regulatory network reveals core and accessory regulations across Pseudomonas aeruginosa lineages. Nucleic Acids Res. 2021;49(20):11476-11490.
Crossref Google Scholar
23

Trouillon J, Sentausa E, Ragno M, et al. Species-specific recruitment of transcription factors dictates toxin expression. Nucleic Acids Res. 2020;48(5):2388-2400.
Crossref Google Scholar
24

Jaini S, Lyubetskaya A, Gomes A, et al. Transcription factor binding site mapping using ChIP-seq. Microbiol Spectr. 2014;2(2):1-21.
Crossref Google Scholar
25

Kang H, Gan J, Zhao J, et al. Crystal structure of Pseudomonas aeruginosa RsaL bound to promoter DNA reaffirms its role as a global regulator involved in quorum-sensing. Nucleic Acids Res. 2017;45(2):699-710.
Crossref Google Scholar
26

Huang H, Shao X, Xie Y, et al. An integrated genomic regulatory network of virulence-related transcriptional factors in Pseudomonas aeruginosa. Nat Commun. 2019;10(1):2931.
Crossref Google Scholar
27

Shao X, Zhang X, Zhang Y, et al. RpoN-dependent direct regulation of quorum sensing and the type Ⅵ secretion system in Pseudomonas aeruginosa PAO1. J Bacteriol. 2018;200(16):e00205-e00218.
Crossref Google Scholar
28

Liang H, Deng X, Li X, Ye Y, Wu M. Molecular mechanisms of master regulator VqsM mediating quorum-sensing and antibiotic resistance in Pseudomonas aeruginosa. Nucleic Acids Res. 2014;42(16):10307-10320.
Crossref Google Scholar
29

Jones CJ, Newsom D, Kelly B, et al. ChIP-Seq and RNA-Seq reveal an AmrZ-mediated mechanism for cyclic di-GMP synthesis and biofilm development by Pseudomonas aeruginosa. PLoS Pathog. 2014;10(3):e1003984.
Crossref Google Scholar
30

An SQ, Valvano MA, Yu YH, Webb JS, Lopez Campos G. An improved bind-n-seq strategy to determine protein-DNA interactions validated using the bacterial transcriptional regulator YipR. BMC Microbiol. 2020;20(1):1.
Crossref Google Scholar
31

Wang T, Sun W, Fan L, et al. An atlas of the binding specificities of transcription factors in Pseudomonas aeruginosa directs prediction of novel regulators in virulence. Elife. 2021;10:e61885.
Crossref Google Scholar
32

Liang H, Deng X, Ji Q, Sun F, Shen T, He C. The Pseudomonas aeruginosa global regulator VqsR directly inhibits QscR to control quorum-sensing and virulence gene expression. J Bacteriol. 2012;194(12):3098-3108.
Crossref Google Scholar
33

Kong W, Zhao J, Kang H, et al. ChIP-seq reveals the global regulator AlgR mediating cyclic di-GMP synthesis in Pseudomonas aeruginosa. Nucleic Acids Res. 2015;43(17):8268-8282.
Crossref Google Scholar
34

Zhao J, Yu X, Zhu M, et al. Structural and molecular mechanism of CdpR involved in quorum-sensing and bacterial virulence in Pseudomonas aeruginosa. PLoS Biol. 2016;14(4):e1002449.
Crossref Google Scholar
35

Song Y, Yang C, Chen G, et al. Molecular insights into the master regulator CysB-mediated bacterial virulence in Pseudomonas aeruginosa. Mol Microbiol. 2019;111(5):1195-1210.
Crossref Google Scholar
36

Sun L, Chi X, Feng Z, et al. phz1 contributes much more to phenazine-1-carboxylic acid biosynthesis than phz2 in Pseudomonas aeruginosa rpoS mutant. J Basic Microbiol. 2019;59(9):914-923.
Crossref Google Scholar
37

Galán-Vásquez E., Luna-Olivera B.C., Ramírez-Ibáñez M., Martínez-Antonio A. RegulomePA: a database of transcriptional regulatory interactions in Pseudomonas aeruginosa PAO1. Database (Oxford). 2020;2020:baaa106.
Crossref Google Scholar
38

Rajput A, Tsunemoto H, Sastry AV, et al. Machine learning from Pseudomonas aeruginosa transcriptomes identifies independently modulated sets of genes associated with known transcriptional regulators. Nucleic Acids Res. 2022;50(7):3658-3672.
Crossref Google Scholar
39

Lee J, Wu J, Deng Y, et al. A cell-cell communication signal integrates quorum sensing and stress response. Nat Chem Biol. 2013;9(5):339-343.
Crossref Google Scholar
40

Schuster M, Lostroh CP, Ogi T, Greenberg EP. Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J Bacteriol. 2003;185(7):2066-2079.
Crossref Google Scholar
41

Wagner VE, Bushnell D, Passador L, Brooks AI, Iglewski BH. Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment. J Bacteriol. 2003;185(7):2080-2095.
Crossref Google Scholar
42

Waters CM, Bassler BL. Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol. 2005;21:319-346.
Crossref Google Scholar
43

Williams P, Camara M. Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr Opin Microbiol. 2009;12(2):182-191.
Crossref Google Scholar
44

Schuster M, Sexton DJ, Diggle SP, Greenberg EP. Acyl-homoserine lactone quorum sensing: from evolution to application. Annu Rev Microbiol. 2013;67:43-63.
Crossref Google Scholar
45

Albus AM, Pesci EC, Runyen-Janecky LJ, West SE, Iglewski BH. H. Vfr controls quorum sensing in Pseudomonas aeruginosa. J Bacteriol. 1997;179(12):3928-3935.
Crossref Google Scholar
46

Balasubramanian D, Kumari H, Jaric M, et al. Deep sequencing analyses expands the Pseudomonas aeruginosa AmpR regulon to include small RNA-mediated regulation of iron acquisition, heat shock and oxidative stress response. Nucleic Acids Res. 2014;42(2):979-998.
Crossref Google Scholar
47

Carty NL, Layland N, Colmer-Hamood JA, Calfee MW, Pesci EC, Hamood AN. PtxR modulates the expression of QS-controlled virulence factors in the Pseudomonas aeruginosa strain PAO1. Mol Microbiol. 2006;61(3):782-794.
Crossref Google Scholar
48

Chugani SA, Whiteley M, Lee KM, D’Argenio D, Manoil C, Greenberg EP. QscR, a modulator of quorum-sensing signal synthesis and virulence in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2001;98(5):2752-2757.
Crossref Google Scholar
49

Siehnel R, Traxler B, An DD, Parsek MR, Schaefer AL, Singh PK. A unique regulator controls the activation threshold of quorum-regulated genes in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2010;107(17):7916-7921.
Crossref Google Scholar
50

Li S, Gong X, Yin L, et al. Acetylation of CspC controls the las quorum-sensing system through translational regulation of rsaL in Pseudomonas aeruginosa. mBio. 2022;13(3):e0054722.
Crossref Google Scholar
51

Zhang Y, Zhou CM, Pu Q, et al. Pseudomonas aeruginosa regulatory protein AnvM controls pathogenicity in anaerobic environments and impacts host defense. mBio. 2019;10(4):e01362-19.
Crossref Google Scholar
52

Sana TG, Lomas R, Gimenez MR, et al. Differential modulation of quorum sensing signaling through QslA in Pseudomonas aeruginosa strains PAO1 and PA14. J Bacteriol. 2019;201(21):e00362-19.
Crossref Google Scholar
53

Kojic M, Jovcic B, Vindigni A, Odreman F, Venturi V. Novel target genes of PsrA transcriptional regulator of Pseudomonas aeruginosa. FEMS Microbiol Lett. 2005;246(2):175-181.
Crossref Google Scholar
54

Wells G, Palethorpe S, Pesci EC. PsrA controls the synthesis of the Pseudomonas aeruginosa quinolone signal via repression of the FadE homolog, PA0506. PLoS One. 2017;12(12):e0189331.
Crossref Google Scholar
55

Mahajan-Miklos S, Tan MW, Rahme LG, Ausubel FM. Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell. 1999;96(1):47-56.
Crossref Google Scholar
56

Wilson R, Sykes DA, Watson D, Rutman A, Taylor GW, Cole PJ. Measurement of Pseudomonas aeruginosa phenazine pigments in sputum and assessment of their contribution to sputum sol toxicity for respiratory epithelium. Infect Immun. 1988;56(9):2515-2517.
Crossref Google Scholar
57

Rampioni G, Schuster M, Greenberg EP, et al. RsaL provides quorum sensing homeostasis and functions as a global regulator of gene expression in Pseudomonas aeruginosa. Mol Microbiol. 2007;66(6):1557-1565.
Crossref Google Scholar
58

Whiteley M, Greenberg EP. Promoter specificity elements in Pseudomonas aeruginosa quorum-sensing-controlled genes. J Bacteriol. 2001;183(19):5529-5534.
Crossref Google Scholar
59

Li C, Wally H, Miller SJ, Lu CD. The multifaceted proteins MvaT and MvaU, members of the H-NS family, control arginine metabolism, pyocyanin synthesis, and prophage activation in Pseudomonas aeruginosa PAO1. J Bacteriol. 2009;191(20):6211-6218.
Crossref Google Scholar
60

Cai Z, Yang F, Shao X, et al. ECF sigma factor HxuI is critical for in vivo fitness of Pseudomonas aeruginosa during infection. Microbiol Spectr. 2022;10(1):e0162021.
Crossref Google Scholar
61

Liang H, Duan J, Sibley CD, Surette MG, Duan K. Identification of mutants with altered phenazine production in Pseudomonas aeruginosa. J Med Microbiol. 2011;60(Pt 1):22-34.
Crossref Google Scholar
62

Lin L, Xu K, Shen D, Chou SH, Gomelsky M, Qian G. Antifungal weapons of Lysobacter, a mighty biocontrol agent. Environ Microbiol. 2021;23(10):5704-5715.
Crossref Google Scholar
63

Starnbach MN, Lory S. The fliA (rpoF) gene of Pseudomonas aeruginosa encodes an alternative sigma factor required for flagellin synthesis. Mol Microbiol. 1992;6(4):459-469.
Crossref Google Scholar
64

Dasgupta N, Wolfgang MC, Goodman AL, et al. A four-tiered transcriptional regulatory circuit controls flagellar biogenesis in Pseudomonas aeruginosa. Mol Microbiol. 2003;50(3):809-824.
Crossref Google Scholar
65

Frisk A, Jyot J, Arora SK, Ramphal R. Identification and functional characterization of flgM, a gene encoding the anti-sigma 28 factor in Pseudomonas aeruginosa. J Bacteriol. 2002;184(6):1514-1521.
Crossref Google Scholar
66

Dasgupta N, Ferrell EP, Kanack KJ, West SE, Ramphal R. fleQ, the gene encoding the major flagellar regulator of Pseudomonas aeruginosa, is sigma70 dependent and is downregulated by Vfr, a homolog of Escherichia coli cyclic AMP receptor protein. J Bacteriol. 2002;184(19):5240-5250.
Crossref Google Scholar
67

Chanchal, Banerjee P, Raghav S, Goswami HN, Jain D. The antiactivator FleN uses an allosteric mechanism to regulate sigma(54)-dependent expression of flagellar genes in Pseudomonas aeruginosa. Sci Adv. 2021;7(43):eabj1792.
Crossref Google Scholar
68

Petrova OE, Schurr JR, Schurr MJ, Sauer K. The novel Pseudomonas aeruginosa two-component regulator BfmR controls bacteriophage-mediated lysis and DNA release during biofilm development through PhdA. Mol Microbiol. 2011;81(3):767-783.
Crossref Google Scholar
69

Wang D, Zhang X, Yin L, et al. RplI interacts with 5’ UTR of exsA to repress its translation and type Ⅲ secretion system in Pseudomonas aeruginosa. PLoS Pathog. 2022;18(1):e1010170.
Crossref Google Scholar
70

Ma Y, Liu Y, Bi Y, et al. OsaR (PA0056) functions as a repressor of the gene fleQ encoding an important motility regulator in Pseudomonas aeruginosa. J Bacteriol. 2021;203(20):e0014521.
Crossref Google Scholar
71

Baraquet C, Harwood CS. FleQ DNA binding consensus sequence revealed by studies of FleQ-dependent regulation of biofilm gene expression in Pseudomonas aeruginosa. J Bacteriol. 2015;198(1):178-186.
Crossref Google Scholar
72

Hickman JW, Harwood CS. Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor. Mol Microbiol. 2008;69(2):376-389.
Crossref Google Scholar
73

Baraquet C, Murakami K, Parsek MR, Harwood CS. The FleQ protein from Pseudomonas aeruginosa functions as both a repressor and an activator to control gene expression from the pel operon promoter in response to c-di-GMP. Nucleic Acids Res. 2012;40(15):7207-7218.
Crossref Google Scholar
74

Wu W, Badrane H, Arora S, Baker HV, Jin S. MucA-mediated coordination of type Ⅲ secretion and alginate synthesis in Pseudomonas aeruginosa. J Bacteriol. 2004;186(22):7575-7585.
Crossref Google Scholar
75

Jones AK, Fulcher NB, Balzer GJ, et al. Activation of the Pseudomonas aeruginosa AlgU regulon through mucA mutation inhibits cyclic AMP/Vfr signaling. J Bacteriol. 2010;192(21):5709-5717.
Crossref Google Scholar
76

Chand NS, Lee JS, Clatworthy AE, Golas AJ, Smith RS, Hung DT. The sensor kinase KinB regulates virulence in acute Pseudomonas aeruginosa infection. J Bacteriol. 2011;193(12):2989-2999.
Crossref Google Scholar
77

Mukherjee S, Jemielita M, Stergioula V, Tikhonov M, Bassler BL. Photosensing and quorum sensing are integrated to control Pseudomonas aeruginosa collective behaviors. PLoS Biol. 2019;17(12):e3000579.
Crossref Google Scholar
78

Romero M, Silistre H, Lovelock L, et al. Genome-wide mapping of the RNA targets of the Pseudomonas aeruginosa riboregulatory protein RsmN. Nucleic Acids Res. 2018;46(13):6823-6840.
Crossref Google Scholar
79

Mikkelsen H, Ball G, Giraud C, Filloux A. Expression of Pseudomonas aeruginosa CupD fimbrial genes is antagonistically controlled by RcsB and the EAL-containing PvrR response regulators. PLoS One. 2009;4(6):e6018.
Crossref Google Scholar
80

Hauser AR, Cobb E, Bodi M, et al. Type Ⅲ protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Crit Care Med. 2002;30(3):521-528.
Crossref Google Scholar
81

Roy-Burman A, Savel RH, Racine S, et al. Type Ⅲ protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections. J Infect Dis. 2001;183(12):1767-1774.
Crossref Google Scholar
82

Crouch Brewer S, Wunderink RG, Jones CB, Leeper KV Jr. Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest. 1996;109(4):1019-1029.
Crossref Google Scholar
83

Bordi C, Lamy MC, Ventre I, et al. Regulatory RNAs and the HptB/RetS signalling pathways fine-tune Pseudomonas aeruginosa pathogenesis. Mol Microbiol. 2010;76(6):1427-1443.
Crossref Google Scholar
84

Williams McMackin EA, Marsden AE, Yahr TL. H-Ns. Family members MvaT and MvaU regulate the Pseudomonas aeruginosa type Ⅲ secretion system. J Bacteriol. 2019;201(14):e00054-19.
Crossref Google Scholar
85

Li K, Xu C, Jin Y, et al. SuhB is a regulator of multiple virulence genes and essential for pathogenesis of Pseudomonas aeruginosa. mBio. 2013;4(6):e00419-13.
Crossref Google Scholar
86

Li K, Yang G, Debru AB, et al. SuhB regulates the motile-sessile switch in Pseudomonas aeruginosa through the Gac/Rsm pathway and c-di-GMP signaling. Front Microbiol. 2017;8:1045.
Crossref Google Scholar
87

Xia Y, Xu C, Wang D, et al. YbeY controls the type Ⅲ and type Ⅵ secretion systems and biofilm formation through RetS in Pseudomonas aeruginosa. Appl Environ Microbiol. 2020;87(5):e02171-20.
Crossref Google Scholar
88

Jin Y, Zhang M, Zhu F, et al. NrtR regulates the type Ⅲ secretion system through cAMP/Vfr pathway in Pseudomonas aeruginosa. Front Microbiol. 2019;10:85.
Crossref Google Scholar
89

Intile PJ, Balzer GJ, Wolfgang MC, Yahr TL. The RNA helicase DeaD stimulates ExsA translation to promote expression of the Pseudomonas aeruginosa type Ⅲ secretion system. J Bacteriol. 2015;197(16):2664-2674.
Crossref Google Scholar
90

Janssen KH, Corley JM, Djapgne L, et al. Hfq and sRNA 179 inhibit expression of the Pseudomonas aeruginosa cAMP-Vfr and type Ⅲ secretion regulons. mBio. 2020;11(3):e00363-20.
Crossref Google Scholar
91

Li S, Weng Y, Li X, et al. Acetylation of the CspA family protein CspC controls the type Ⅲ secretion system through translational regulation of exsA in Pseudomonas aeruginosa. Nucleic Acids Res. 2021;49(12):6756-6770.
Crossref Google Scholar
92

Mougous JD, Cuff ME, Raunser S, et al. A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science. 2006;312(5779):1526-1530.
Crossref Google Scholar
93

Marden JN, Diaz MR, Walton WG, et al. An unusual CsrA family member operates in series with RsmA to amplify posttranscriptional responses in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2013;110(37):15055-15060.
Crossref Google Scholar
94

Zhang X, Yin L, Liu Q, et al. NrtR mediated regulation of H1-T6SS in Pseudomonas aeruginosa. Microbiol Spectr. 2022;10(1):e0185821.
Crossref Google Scholar
95

Zhou T, Huang J, Liu Z, Lin Q, Xu Z, Zhang LH. The two-component system FleS/FleR represses H1-T6SS via cyclic di-GMP signaling in Pseudomonas aeruginosa. Appl Environ Microbiol. 2022;88(2):e0165521.
Crossref Google Scholar
96

Chen PR, Bae T, Williams WA, et al. An oxidation-sensing mechanism is used by the global regulator MgrA in Staphylococcus aureus. Nat Chem Biol. 2006;2(11):591-595.
Crossref Google Scholar
97

Fuangthong M, Helmann JD. The OhrR repressor senses organic hydroperoxides by reversible formation of a cysteine-sulfenic acid derivative. Proc Natl Acad Sci U S A. 2002;99(10):6690-6695.
Crossref Google Scholar
98

Fujimoto DF, Higginbotham RH, Sterba KM, et al. Staphylococcus aureus SarA is a regulatory protein responsive to redox and pH that can support bacteriophage lambda integrase-mediated excision/recombination. Mol Microbiol. 2009;74(6):1445-1458.
Crossref Google Scholar
99

Palma M, Zurita J, Ferreras JA, et al. Pseudomonas aeruginosa SoxR does not conform to the archetypal paradigm for SoxR-dependent regulation of the bacterial oxidative stress adaptive response. Infect Immun. 2005;73(5):2958-2966.
Crossref Google Scholar
100

Dietrich LE, Teal TK, Price-Whelan A, Newman DK. Redox-active antibiotics control gene expression and community behavior in divergent bacteria. Science. 2008;321(5893):1203-1206.
Crossref Google Scholar
101

Vinckx T, Matthijs S, Cornelis P. Loss of the oxidative stress regulator OxyR in Pseudomonas aeruginosa PAO1 impairs growth under iron-limited conditions. FEMS Microbiol Lett. 2008;288(2):258-265.
Crossref Google Scholar
102

Ochsner UA, Vasil ML, Alsabbagh E, Parvatiyar K, Hassett DJ. Role of the Pseudomonas aeruginosa oxyR-recG operon in oxidative stress defense and DNA repair: OxyR-dependent regulation of katB-ankB, ahpB, and ahpC-ahpF. J Bacteriol. 2000;182(16):4533-4544.
Crossref Google Scholar
103

Vinckx T, Wei Q, Matthijs S, Cornelis P. The Pseudomonas aeruginosa oxidative stress regulator OxyR influences production of pyocyanin and rhamnolipids: protective role of pyocyanin. Microbiology (Read). 2010;156(Pt 3):678-686.
Crossref Google Scholar
104

Lan L, Murray TS, Kazmierczak BI, He C. Pseudomonas aeruginosa OspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection. Mol Microbiol. 2010;75(1):76-91.
Crossref Google Scholar
105

Chen H, Hu J, Chen PR, et al. The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanism. Proc Natl Acad Sci U S A. 2008;105(36):13586-13591.
Crossref Google Scholar
106

Deng X, Weerapana E, Ulanovskaya O, et al. Proteome-wide quantification and characterization of oxidation-sensitive cysteines in pathogenic bacteria. Cell Host Microbe. 2013;13(3):358-370.
Crossref Google Scholar
107

Xuan G, Lv C, Xu H, et al. Sulfane sulfur regulates LasR-mediated quorum sensing and virulence in Pseudomonas aeruginosa PAO1. Antioxidants. 2021;10(9):1498.
Crossref Google Scholar
108

Kafle P, Amoh AN, Reaves JM, et al. Molecular insights into the impact of oxidative stress on the quorum-sensing regulator protein LasR. J Biol Chem. 2016;291(22):11776-11786.
Crossref Google Scholar
109

Shlyueva D, Stampfel G, Stark A. Transcriptional enhancers: from properties to genome-wide predictions. Nat Rev Genet. 2014;15(4):272-286.
Crossref Google Scholar
110

Rosenberg G, Riquelme S, Prince A, Avraham R. Immunometabolic crosstalk during bacterial infection. Nat Microbiol. 2022;7(4):497-507.
Crossref Google Scholar
111

Bartell JA, Blazier AS, Yen P, et al. Reconstruction of the metabolic network of Pseudomonas aeruginosa to interrogate virulence factor synthesis. Nat Commun. 2017;8:14631.
Crossref Google Scholar
112

Panayidou S, Georgiades K, Christofi T, Tamana S, Promponas VJ, Apidianakis Y. Pseudomonas aeruginosa core metabolism exerts a widespread growth-independent control on virulence. Sci Rep. 2020;10(1):9505.
Crossref Google Scholar
113

Chavali AK, D’Auria KM, Hewlett EL, Pearson RD, Papin JA. A metabolic network approach for the identification and prioritization of antimicrobial drug targets. Trends Microbiol. 2012;20(3):113-123.
Crossref Google Scholar
114

Mienda BS, Salihu R, Adamu A, Idris S. Genome-scale metabolic models as platforms for identification of novel genes as antimicrobial drug targets. Future Microbiol. 2018;13:455-467.
Crossref Google Scholar
115

Oberhardt MA, Puchałka J, Fryer KE, Martins dos Santos VA, Papin JA. Genome-scale metabolic network analysis of the opportunistic pathogen Pseudomonas aeruginosa PAO1. J Bacteriol. 2008;190(8):2790-2803.
Crossref Google Scholar
116

Müh U, Schuster M, Heim R, Singh A, Olson ER, Greenberg EP. Novel Pseudomonas aeruginosa quorum-sensing inhibitors identified in an ultra-high-throughput screen. Antimicrob Agents Chemother. 2006;50(11):3674-3679.
Crossref Google Scholar
117

Starkey M, Lepine F, Maura D, et al. Identification of anti-virulence compounds that disrupt quorum-sensing regulated acute and persistent pathogenicity. PLoS Pathog. 2014;10(8):e1004321.
Crossref Google Scholar
118

Imperi F, Massai F, Facchini M, et al. Repurposing the antimycotic drug flucytosine for suppression of Pseudomonas aeruginosa pathogenicity. Proc Natl Acad Sci U S A. 2013;110(18):7458-7463.
Crossref Google Scholar
119

Borlee BR, Geske GD, Blackwell HE, Handelsman J. Identification of synthetic inducers and inhibitors of the quorum-sensing regulator LasR in Pseudomonas aeruginosa by high-throughput screening. Appl Environ Microbiol. 2010;76(24):8255-8258.
Crossref Google Scholar
120

van Tilburg Bernardes E, Charron-Mazenod L, Reading DJ, Reckseidler-Zenteno SL, Lewenza S. Exopolysaccharide-repressing small molecules with antibiofilm and antivirulence activity against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2017;61(5):e01997-16.
Crossref Google Scholar
121

Aiello D, Williams JD, Majgier-Baranowska H, et al. Discovery and characterization of inhibitors of Pseudomonas aeruginosa type Ⅲ secretion. Antimicrob Agents Chemother. 2010;54(5):1988-1999.
Crossref Google Scholar
122

Zhu J, Cai X, Harris TL, et al. Disarming Pseudomonas aeruginosa virulence factor LasB by leveraging a Caenorhabditis elegans infection model. Chem Biol. 2015;22(4):483-491.
Crossref Google Scholar
123

Abelyan N, Grabski H, Tiratsuyan S. In silico screening of flavones and its derivatives as potential inhibitors of quorum-sensing regulator LasR of Pseudomonas aeruginosa. Mol Biol. 2020;54(1):153-163.
Crossref Google Scholar
124

Shaker B, Ahmad S, Thai TD, Eyun SI, Na D. Rational drug design for Pseudomonas aeruginosa PqsA enzyme: an in silico guided study to block biofilm formation. Front Mol Biosci. 2020;7:577316.
Crossref Google Scholar
125

Vetrivel A, Natchimuthu S, Subramanian V, Murugesan R. High-throughput virtual screening for a new class of antagonist targeting LasR of Pseudomonas aeruginosa. ACS Omega. 2021;6(28):18314-18324.
Crossref Google Scholar
126

Baloyi IT, Adeosun IJ, Yusuf AA, Cosa S. In silico and in vitro screening of antipathogenic properties of melianthus comosus (Vahl) against Pseudomonas aeruginosa. Antibiotics. 2021;10(6):679.
Crossref Google Scholar
127

Tajani AS, Jangi E, Davodi M, et al. Anti-quorum sensing potential of ketoprofen and its derivatives against Pseudomonas aeruginosa: insights to in silico and in vitro studies. Arch Microbiol. 2021;203(8):5123-5132.
Crossref Google Scholar
128

Behera SK, Panda AK, Mishra R, Mahanty A, Bisht SS. Structure based virtual screening and molecular dynamics of natural anti-biofilm compounds against SagS response regulator/sensor kinase in Pseudomonas aeruginosa. J Biomol Struct Dyn. 2022:1-16.
Crossref Google Scholar
129

Deng X, Chen K, Luo GZ, et al. Widespread occurrence of N6-methyladenosine in bacterial mRNA. Nucleic Acids Res. 2015;43(13):6557-6567.
Crossref Google Scholar
130

Shao X, Zhang W, Umar MI, et al. RNA G-quadruplex structures mediate gene regulation in bacteria. mBio. 2020;11(1):e02926-19.
Crossref Google Scholar
131

Smith EE, Buckley DG, Wu Z, et al. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci U S A. 2006;103(22):8487-8492.
Crossref Google Scholar
132

Yang L, Jelsbak L, Marvig RL, et al. Evolutionary dynamics of bacteria in a human host environment. Proc Natl Acad Sci U S A. 2011;108(18):7481-7486.
Crossref Google Scholar
133

Hoffman LR, Kulasekara HD, Emerson J, et al. Pseudomonas aeruginosa lasR mutants are associated with cystic fibrosis lung disease progression. J Cyst Fibros. 2009;8(1):66-70.
Crossref Google Scholar
134

Folkesson A, Jelsbak L, Yang L, et al. Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective. Nat Rev Microbiol. 2012;10(12):841-851.
Crossref Google Scholar
135

Valentini M, Gonzalez D, Mavridou DA, Filloux A. Lifestyle transitions and adaptive pathogenesis of Pseudomonas aeruginosa. Curr Opin Microbiol. 2018;41:15-20.
Crossref Google Scholar
136

Ahmed SAKS, Rudden M, Elias SM, et al. Pseudomonas aeruginosa PA80 is a cystic fibrosis isolate deficient in RhlRI quorum sensing. Sci Rep. 2021;11(1):5729.
Crossref Google Scholar
137

Boşgelmez-Tinaz G, Ulusoy S. Characterization of N-butanoyl-L-homoserine lactone (C4-HSL) deficient clinical isolates of Pseudomonas aeruginosa. Microb Pathog. 2008;44(1):13-19.
Crossref Google Scholar
138

Martínez-Carranza E, García-Reyes S, González-Valdez A, Soberón-Chávez G. Tracking the genome of four Pseudomonas aeruginosa isolates that have a defective Las quorum-sensing system, but are still virulent. Access Microbiol. 2020;2(7):acmi000132.
Crossref Google Scholar
139

Shang Z, Wang H, Zhou S, Chu W. Characterization of N-Acyl-homoserine lactones (AHLs)-deficient clinical isolates of Pseudomonas aeruginosa. Indian J Microbiol. 2014;54(2):158-162.
Crossref Google Scholar
140

Baker P, Hill PJ, Snarr BD, et al. Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms. Sci Adv. 2016;2(5):e1501632.
Crossref Google Scholar
141

Das T, Simone M, Ibugo AI, Witting PK, Manefield M, Manos J. Glutathione enhances antibiotic efficiency and effectiveness of DNase Ⅰ in disrupting Pseudomonas aeruginosa biofilms while also inhibiting pyocyanin activity, thus facilitating restoration of cell enzymatic activity, confluence and viability. Front Microbiol. 2017;8:2429.
Crossref Google Scholar
142

Singh N, Romero M, Travanut A, et al. Dual bioresponsive antibiotic and quorum sensing inhibitor combination nanoparticles for treatment of Pseudomonas aeruginosa biofilms in vitro and ex vivo. Biomater Sci. 2019;7(10):4099-4111.
Crossref Google Scholar
Genes & Diseases
Volume 10 Issue 5,
September 2023
Pages 2049-2063
DOI: 10.1016/j.gendis.2022.09.009
Cite this article:
Shao X, Yao C, Ding Y, et al. The transcriptional regulators of virulence for Pseudomonas aeruginosa: Therapeutic opportunity and preventive potential of its clinical infections. Genes & Diseases, 2023, 10(5): 2049-2063. https://doi.org/10.1016/j.gendis.2022.09.009

287

Views

3

Downloads

7

Crossref

6

Web of Science

6

Scopus

0

CSCD

Altmetrics
Received: 13 May 2022
Accepted: 21 September 2022
Published: 01 October 2022
© 2022 The Authors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return