Antivirulent Properties of the Adamantane Derivative 4-(Adamanthyl-1)-1-(1-Aminobutyl) Benzene Against Pseudomonas Aeruginosa
DOI:
https://doi.org/10.20535/ibb.2023.7.3.282006Keywords:
adamantane derivative, Pseudomonas aeruginosa, gene expression, Quorum sensing, virulence factorsAbstract
Background. Pseudomonas aeruginosa is an opportunistic pathogen characterized by a high level of virulence and classified as a microorganism with a critical priority for the development of new antimicrobial drugs. Targeting virulence factors is one of the promising approaches in antimicrobial drug development.
Objective. Investigating the antivirulence properties of the aminoadamantane derivative 4-(adamantyl-1)-1-(1-aminobutyl)benzene against P. aeruginosa.
Methods. The minimum inhibitory concentration (MIC) of 4-(adamantyl-1)-1-(1-aminobutyl)benzene (code AM-166) against the clinical strain P. aeruginosa 449 was determined using the serial microdilution method. We conducted quantitative real-time PCR to assess the impact of AM-166 on gene expression. Additionally, we investigated the synthesis of pyocyanin, hemolytic and protease activity, as well as motility of P. aeruginosa under the influence of AM-166.
Results. The obtained data indicate that the MIC of the AM-166 compound is 100 μg/ml. When exposed to AM-166 (at 0.5 MIC), we observed a decrease in the transcriptional activity of the lasI, lasR, pqsR, aprA, exoA, and exoS genes, along with an increase in the expression of the rhlR gene. Notably, AM-166 did not alter the expression of the toxA gene. Furthermore, AM-166 increased the production of pyocyanin, had no significant effect on protease activity, and inhibited both hemolytic activity and motility in P. aeruginosa 449.
Conclusions. The adamantane derivative AM-166 disrupts the functioning of the Quorum sensing systems and pathogenicity of P. aeruginosa while also altering the expression of genes that regulate the synthesis of virulence factors.
References
Moradali MF, Ghods S, Rehm BH. Pseudomonas aeruginosa Lifestyle: A paradigm for adaptation, survival, and persistence. Front Cell Infect Microbiol. 2017 Feb 15; 7:39. DOI:10.3389/fcimb.2017.00039
Jamal M, Ahmad W, Andleeb S, Jalil F, Imran M, Nawaz MA, et al. Bacterial biofilm and associated infections. J Chin Med Assoc. 2018 Jan;81(1):7-11. DOI: 10.1016/j.jcma.2017.07.012
Liao C, Huang X, Wang Q, Yao D, Lu W. Virulence factors of Pseudomonas aeruginosa and antivirulence strategies to combat its drug resistance. Front Cell Infect Microbiol. 2022 Jul 6;12:926758. DOI: 10.3389/fcimb.2022.926758
Jurado-Martín I, Sainz-Mejías M, McClean S. Pseudomonas aeruginosa: An audacious pathogen with an adaptable arsenal of virulence factors. Int J Mol Sci. 2021 Mar 18;22(6):3128. DOI: 10.3390/ijms22063128
Santajit S, Sookrung N, Indrawattana N. Quorum Sensing in ESKAPE Bugs: A target for combating antimicrobial resistance and bacterial virulence. Biology (Basel). 2022 Oct 6;11(10):1466. DOI: 10.3390/biology11101466
Madukoma CS, Liang P, Dimkovikj A, Chen J, Lee SW, Chen DZ, et al. Single cells exhibit differing behavioral phases during early stages of Pseudomonas aeruginosa swarming. J Bacteriol. 2019 Sep 6;201(19):e00184-19. DOI: 10.1128/JB.00184-19
Coleman SR, Blimkie T, Falsafi R, Hancock REW. Multidrug adaptive resistance of Pseudomonas aeruginosa swarming cells. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01999-19. DOI: 10.1128/AAC.01999-19
Chadha J, Harjai K, Chhibber S. Revisiting the virulence hallmarks of Pseudomonas aeruginosa: a chronicle through the perspective of quorum sensing. Environ Microbiol. 2022 Jun; 24(6):2630-56. DOI: 10.1111/1462-2920.15784
Sintchenko V, Timms V, Sim E, Rockett R, Bachmann N, O'Sullivan M, et al. Microbial genomics as a catalyst for targeted antivirulence therapeutics. Front Med (Lausanne). 2021 Apr 13;8:641260. DOI: 10.3389/fmed.2021.641260
D'Angelo F, Baldelli V, Halliday N, Pantalone P, Polticelli F, Fiscarelli E, et al. Identification of FDA-approved drugs as antivirulence agents targeting the pqs quorum-sensing system of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2018 Oct 24;62:e01296-18. DOI: 10.1128/AAC.01296-18
Imperi F, Chen W, Smani Y. Editorial: Antivirulence drugs against bacterial infections. Front. Microbiol. 2021 May 25;12:690672. DOI: 10.3389/fmicb.2021.690672
Spilovska K, Zemek F, Korabecny J, Nepovimova E, Soukup O, Windisch M, et al. Adamantane - A lead structure for drugs in clinical practice. Curr Med Chem. 2016;23(29):3245-66. DOI: 10.2174/0929867323666160525114026
Rusu A, Tanase C, Pascu GA, Todoran N. Recent advances regarding the therapeutic potential of adapalene. Pharmaceuticals (Basel). 2020 Aug 28;13(9):217. DOI: 10.3390/ph13090217
Cheng AV, Kim W, Escobar IE, Mylonakis E, Wuest WM. Structure-activity relationship and anticancer profile of second-generation anti-MRSA synthetic retinoids. ACS Med Chem Lett. 2019 Jul 17;11(3):393-7. DOI: 10.1021/acsmedchemlett.9b00159
Tan F, She P, Zhou L, Liu Y, Chen L, Luo Z, et al. Bactericidal and anti-biofilm activity of the retinoid compound CD437 against Enterococcus faecalis. Front Microbiol. 2019 Oct 9;10:2301. DOI: 10.3389/fmicb.2019.02301
Trognon J, Vera G, Rima M, Stigliani JL, Amielet L, El Hage S, et al. Investigation of direct and retro chromone-2-carboxamides based analogs of Pseudomonas aeruginosa Quorum Sensing signal as new anti-biofilm agents. Pharmaceuticals (Basel). 2022 Mar 29;15(4):417. DOI: 10.3390/ph15040417
Emam A, Carter WG, Lingwood C. Glycolipid-dependent, protease sensitive internalization of Pseudomonas aeruginosa into cultured human respiratory epithelial cells. Open Microbiol J. 2010 Dec 13;4:106-15. DOI: 10.2174/1874285801004010106
International Standards Organization. ISO 20776-1:2019. Susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility test devices - Part 1: Broth micro-dilution reference method for testing the in vitro activity of antimicrobial agents against rapidly growing aerobic bacteria involved in infectious diseases. Geneva: ISO; 2019.
Essar DW, Eberly L, Hadero A, Crawford IP. Identification and characterization of genes for a second anthranilate synthase in Pseudomonas aeruginosa: interchangeability of the two anthranilate synthases and evolutionary implications. J Bacteriol. 1990 Feb;172(2):884-900. DOI: 10.1128/jb.172.2.884-900.1990
Lankisch PG, Vogt W. Direct haemolytic activity of phospholipase A. Biochim Biophys Acta. 1972 Jun 19;270(2):241-7. DOI: 10.1016/0005-2760(72)90235-4
Montville TJ. Dual-substrate plate diffusion assay for proteases. Appl Environ Microbiol. 1983 Jan;45(1):200-4. DOI: 10.1128/aem.45.1.200-204.1983
Fonseca AP, Sousa JC. Effect of antibiotic-induced morphological changes on surface properties, motility and adhesion of nosocomial Pseudomonas aeruginosa strains under different physiological states. J Appl Microbiol. 2007 Nov;103(5):1828-37. DOI: 10.1111/j.1365-2672.2007.03422.x
Kinscherf TG, Willis DK. Swarming by Pseudomonas syringae B728a requires gacS (lemA) and gacA but not the acyl-homoserine lactone biosynthetic gene ahlI. J Bacteriol. 1999 Jul;181(13):4133-6. DOI: 10.1128/JB.181.13.4133-4136.1999
Dashti AA, Jadaon MM, Abdulsamad AM, Dashti HM. Heat treatment of bacteria: A simple method of DNA extraction for molecular techniques. Kuwait Med. J. 2009 Jun;41:117-22.
El-Mowafy SA, Abd El Galil KH, El-Messery SM, Shaaban MI. Aspirin is an efficient inhibitor of quorum sensing, virulence and toxins in Pseudomonas aeruginosa. Microb Pathog. 2014 Sep;74:25-32. DOI: 10.1016/j.micpath.2014.07.008.
Joly B, Pierre M, Auvin S, Colin F, Gottrand F, Guery B, et al. Relative expression of Pseudomonas aeruginosa virulence genes analyzed by a real time RT-PCR method during lung infection in rats. FEMS Microbiol Lett. 2005 Feb 1;243(1):271-8. DOI: 10.1016/j.femsle.2004.12.012
Khattab MA, Nour MS, Sheshtawy NM. Genetic identification of Pseudomonas aeruginosa virulence genes among different isolates. J Microb Biochem Technol. 2015 Jan;7(5):274-7. DOI:10.4172/1948-5948.1000224
Ghanbarzadeh Corehtash Z, Khorshidi A, Firoozeh F, Akbari H, Mahmoudi Aznaveh A. Biofilm formation and virulence factors among Pseudomonas aeruginosa isolated from burn patients. Jundishapur J Microbiol. 2015 Oct 21;8(10):e22345. DOI: 10.5812/jjm.22345
Lenz AP, Williamson KS, Pitts B, Stewart PS, Franklin MJ. Localized gene expression in Pseudomonas aeruginosa biofilms. Appl Environ Microbiol. 2008 Jul;74(14):4463-71. DOI: 10.1128/AEM.00710-08
Shigemura K, Osawa K, Kato A, Tokimatsu I, Arakawa S, Shirakawa T, et al. Association of overexpression of efflux pump genes with antibiotic resistance in Pseudomonas aeruginosa strains clinically isolated from urinary tract infection patients. J Antibiot (Tokyo). 2015 Sep;68(9):568-72. DOI: 10.1038/ja.2015.34
Birmes FS, Säring R, Hauke MC, Ritzmann NH, Drees SL, Daniel J, et al. Interference with Pseudomonas aeruginosa quorum sensing and virulence by the mycobacterial Pseudomonas quinolone signal dioxygenase AqdC in combination with the N-Acylhomoserine lactone lactonase QsdA. Infect Immun. 2019 Sep 19;87(10):e00278-19. DOI: 10.1128/IAI.00278-19
Zelena L, Gretsky І, Gromozova Е. Influence of ultrahigh frequency irradiation on Photobacterium phosphoreum luxb gene expression. Cent Eur J Biol. 2014 Aug;9(10):1004-10. DOI: 10.2478/s11535-014-0347-5
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001 Dec;25(4):402-8. DOI: 10.1006/meth.2001.1262
Lee J, Zhang L. The hierarchy quorum sensing network in Pseudomonas aeruginosa. Protein Cell. 2015 Jan;6(1):26-41. DOI: 10.1007/s13238-014-0100-x
Smith RS, Iglewski BH. Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target. J Clin Invest. 2003 Nov;112(10):1460-5. DOI: 10.1172/JCI20364
Michalska M, Wolf P. Pseudomonas Exotoxin A: optimized by evolution for effective killing. Front Microbiol. 2015 Sep 15;6:963. DOI: 10.3389/fmicb.2015.00963
Zhu K, Sysoeva TA. Universal antibiotic tolerance arising from antibiotic-triggered accumulation of pyocyanin in Pseudomonas aeruginosa. PLoS Biol. 2019 Dec;17(12):e3000573. DOI: 10.1371/journal.pbio.3000573
Galkіn MB, Ivanytsіa VO. Pseudomonas aeruginosa pyocyanin biosynthesis in presence of porphyrines bismuth complexes and quorum sensing autoinducers. Microbiol Biotechnol. 2013;1(21):23-36. DOI: 10.18524/2307-4663.2013.1(21).48720
Horna G, Ruiz J. Type 3 secretion system of Pseudomonas aeruginosa. Microbiol Res. 2021 May;246:126719. DOI: 10.1016/j.micres.2021.126719
Francis VI, Stevenson EC, Porter SL. Two-component systems required for virulence in Pseudomonas aeruginosa. FEMS Microbiol Lett. 2017 June;364(11):fnx104. DOI: 10.1093/femsle/fnx104
Guo Q, Kong W, Jin S, Chen L, Xu Y, Duan K. PqsR-dependent and PqsR-independent regulation of motility and biofilm formation by PQS in Pseudomonas aeruginosa PAO1. J Basic Microbiol. 2014 Jul;54(7):633-43. DOI: 10.1002/jobm.201300091
Li Y, Bai F, Xia H, Zhuang L, Xu H, Jin Y, et al. A novel regulator PA5022 (aefA) is involved in swimming motility, biofilm formation and elastase activity of Pseudomonas aeruginosa. Microbiol Res. 2015 Jul;176:14-20. DOI: 10.1016/j.micres.2015.04.001
Khan F, Pham DTN, Oloketuyi SF, Kim YM. Regulation and controlling the motility properties of Pseudomonas aeruginosa. Appl Microbiol Biotechnol. 2020 Jan;104(1):33-49. DOI: 10.1007/s00253-019-10201-w
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