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Antimicrobial Proficiency of Amlodipine: Investigating its Impact on Pseudomonas spp. in Urinary Tract Infections

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Abstract

Antibiotic resistance in urinary tract infections (UTIs) is a growing concern due to extensive antibiotic use. The study explores a drug repurposing approach to find non-antibiotic drugs with antibacterial activity. In the present study, 8 strains of Pseudomonas spp. were used that were clinically isolated from UTI-infected patients. Amlodipine, a cardiovascular drug used in this study, has shown potential antimicrobial effect in reducing the various virulence factors, including swimming and twitching motility, biofilm, rhamnolipid, pyocyanin, and oxidative stress resistance against all the strains. Amlodipine exhibited the most potent antimicrobial activity with MIC in the range of 6.25 to 25 µg/ml. Significant inhibition in biofilm production was seen in the range of 45.75 to 76.70%. A maximum decrease of 54.66% and 59.45% in swimming and twitching motility was observed, respectively. Maximum inhibition of 65.87% of pyocyanin pigment was observed with the effect of amlodipine. Moreover, a significant decrease in rhamnolipids production observed after amlodipine treatment was between 16.5 and 0.001 mg/ml as compared to the control. All bacterial strains exhibited leakage of proteins and nucleic acids from their cell membranes when exposed to amlodipine which suggests the damage of the structural integrity. In conclusion, amlodipine exhibited good antimicrobial activity and can be used as a potential candidate to be repurposed for the treatment of urinary tract infections.

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References

  1. Kamurai B, Mombeshora M, Mukanganyama S, Khamesipour F (2020) Repurposing of Drugs for Antibacterial Activities on Selected ESKAPE Bacteria Staphylococcus aureus and Pseudomonas aeruginosa. Int J Microbiol 2020:1–9. https://doi.org/10.1155/2020/8885338

    Article  CAS  Google Scholar 

  2. Foletto VS, da Rosa TF, Serafin MB et al (2021) Repositioning of non-antibiotic drugs as an alternative to microbial resistance: A systematic review. Int J Antimicrob Agents 58:106380

    Article  CAS  PubMed  Google Scholar 

  3. Bansal KK, Goyal R, Sharma A et al (2023) Repurposing of Drugs for the Treatment of Microbial Diseases. Drug Repurposing for Emerging Infectious Diseases and Cancer. Springer, Cham, pp 347–394

    Chapter  Google Scholar 

  4. Gupta P, Chanda R, Rai N et al (2016) Antihypertensive, amlodipine besilate inhibits growth and biofilm of human fungal pathogen Candida. Assay Drug Dev Technol 14:291–297

    Article  CAS  PubMed  Google Scholar 

  5. Reimão JQ, Mesquita JT, Ferreira DD, Tempone AG (2016) Investigation of calcium channel blockers as antiprotozoal agents and their interference in the metabolism of Leishmania (L.) infantum. Evid-Based Complement Alternat Med. https://doi.org/10.1155/2016/1523691

    Article  PubMed  PubMed Central  Google Scholar 

  6. Laudy AE, Kulińska E, Tyski S (2017) The impact of efflux pump inhibitors on the activity of selected non-antibiotic medicinal products against Gram-negative bacteria. Molecules 22:114

    Article  PubMed  PubMed Central  Google Scholar 

  7. Coelho SS, da Rosa TF, Rampelotto RF et al (2021) Amlodipine repositioning: scientific studies and synergistic effects. Am J Ther 28:e772–e776

    Article  Google Scholar 

  8. Hegazy WAH, Khayat MT, Ibrahim TS et al (2020) Repurposing anti-diabetic drugs to cripple quorum sensing in pseudomonas aeruginosa. Microorganisms 8:1285. https://doi.org/10.3390/microorganisms8091285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lescat M, Poirel L, Tinguely C, Nordmann P (2019) A resazurin reduction-based assay for rapid detection of polymyxin resistance in acinetobacter baumannii and Pseudomonas aeruginosa. J Clin Microbiol. https://doi.org/10.1128/JCM.01563-18

    Article  PubMed  PubMed Central  Google Scholar 

  10. Costa P, Gomes ATPC, Braz M et al (2021) Application of the resazurin cell viability assay to monitor Escherichia coli and Salmonella typhimurium inactivation mediated by phages. Antibiotics 10:974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Abbas HA, Hegazy WAH (2020) Repurposing anti-diabetic drug “Sitagliptin” as a novel virulence attenuating agent in Serratia marcescens. PLoS ONE 15:e0231625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Abbas HA, Elsherbini AM, Shaldam MA (2017) Repurposing metformin as a quorum sensing inhibitor in Pseudomonas aeruginosa. African Health Sci 17:808–819

    Article  Google Scholar 

  13. Das T, Manefield M (2012) Pyocyanin promotes extracellular DNA release in Pseudomonas aeruginosa

  14. Hassett DJ, Schweizer HP, Ohman DE (1995) Pseudomonas aeruginosa sodA and sodB mutants defective in manganese-and iron-cofactored superoxide dismutase activity demonstrate the importance of the iron-cofactored form in aerobic metabolism. J Bacteriol 177:6330–6337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Irorere VU, Tripathi L, Marchant R et al (2017) Microbial rhamnolipid production: a critical re-evaluation of published data and suggested future publication criteria. Appl Microbiol Biotechnol 101:3941–3951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Abalos A, Pinazo A, Infante MR et al (2001) Physicochemical and Antimicrobial Properties of New Rhamnolipids Produced by Pseudomonas a eruginosa AT10 from soybean oil refinery wastes. Langmuir 17:1367–1371. https://doi.org/10.1021/la0011735

    Article  CAS  Google Scholar 

  17. Cheng T, Liang J, He J et al (2017) A novel rhamnolipid-producing Pseudomonas aeruginosa ZS1 isolate derived from petroleum sludge suitable for bioremediation. AMB Express 7:120. https://doi.org/10.1186/s13568-017-0418-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Devi KP, Nisha SA, Sakthivel R, Pandian SK (2010) Eugenol (an essential oil of clove) acts as an antibacterial agent against Salmonella typhi by disrupting the cellular membrane. J Ethnopharmacol 130:107–115

    Article  CAS  PubMed  Google Scholar 

  19. Chong H, Li Q (2017) Microbial production of rhamnolipids: opportunities, challenges and strategies. Microb Cell Fact 16:1–12

    Article  Google Scholar 

  20. Soberón-Chávez G, González-Valdez A, Soto-Aceves MP, Cocotl-Yañez M (2021) Rhamnolipids produced by Pseudomonas: from molecular genetics to the market. Microb Biotechnol 14:136–146

    Article  PubMed  Google Scholar 

  21. Zhou K, Zhou W, Li P et al (2008) Mode of action of pentocin 31–1: An antilisteria bacteriocin produced by Lactobacillus pentosus from Chinese traditional ham. Food Control 19:817–822

    Article  CAS  Google Scholar 

  22. Bajpai VK, Ajay Sharma AS, Baek KwangHyun BK (2014) Antibacterial mode of action of the essential oil obtained from Chamaecyparis obtusa sawdust on the membrane integrity of selected foodborne pathogens. Food Technol Biotechnol 52:109

    Google Scholar 

  23. Almeida HMD e S, Brandão LBS, de Melo TR, Ferreira SB (2022) Anti-Bacterial Perspective of Non-Antibiotic Drugs. In: Medical Sciences Forum. MDPI, p 22

  24. Mazumdar K, Kumar KA, Dutta NK (2010) Potential role of the cardiovascular non-antibiotic (helper compound) amlodipine in the treatment of microbial infections: scope and hope for the future. Int J Antimicrob Agents 36:295–302

    Article  CAS  PubMed  Google Scholar 

  25. Kumar KA, Ganguly K, Mazumdar K et al (2003) Amlodipine: a cardiovascular drug with powerful antimicrobial property. Acta Microbiol Pol 52:285–292

    CAS  PubMed  Google Scholar 

  26. Hauser AR (2009) The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nat Rev Microbiol 7:654–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zygiel EM, Nelson CE, Brewer LK et al (2019) The human innate immune protein calprotectin induces iron starvation responses in Pseudomonas aeruginosa. J Biol Chem 294:3549–3562. https://doi.org/10.1074/jbc.RA118.006819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yan Z, **a L, Xu X et al (2023) Exploring calcium channel blocker as a candidate drug for Pseudomonas aeruginosa through network pharmacology and experimental validation. Chem Biol Drug Des 102:1353–1366

    Article  CAS  PubMed  Google Scholar 

  29. Kumar R, Kaur M, Bahia MS, Silakari O (2014) Synthesis, cytotoxic study and docking based multidrug resistance modulator potential analysis of 2-(9-oxoacridin-10 (9H)-yl)-N-phenyl acetamides. Eur J Med Chem 80:83–91

    Article  CAS  PubMed  Google Scholar 

  30. Hu C, Li Y, Zhao Z et al (2018) In vitro synergistic effect of amlodipine and imipenem on the expression of the AdeABC efflux pump in multidrug-resistant Acinetobacter baumannii. PLoS ONE 13:e0198061

    Article  PubMed  PubMed Central  Google Scholar 

  31. Elkhatib WF, Haynes VL, Noreddin AM (2009) Microbiological appraisal of levofloxacin activity against Pseudomonas aeruginosa biofilm in combination with different calcium channel blockers in vitro. J Chemother 21:135–143

    Article  CAS  PubMed  Google Scholar 

  32. Veesenmeyer JL, Hauser AR, Lisboa T, Rello J (2009) Pseudomonas aeruginosa virulence and therapy: evolving translational strategies. Crit Care Med 37:1777

    Article  PubMed  PubMed Central  Google Scholar 

  33. Poole K (2011) Pseudomonas aeruginosa: resistance to the max. Front Microbiol 2:65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gellatly SL, Hancock REW (2013) Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. Pathog Dis 67:159–173

    Article  CAS  PubMed  Google Scholar 

  35. Newman JW, Floyd RV, Fothergill JL (2017) The contribution of Pseudomonas aeruginosa virulence factors and host factors in the establishment of urinary tract infections. FEMS Microbiol Lett 364:fnx124

    Article  Google Scholar 

  36. Liao C, Huang X, Wang Q et al (2022) Virulence factors of Pseudomonas aeruginosa and antivirulence strategies to combat its drug resistance. Front Cell Infect Microbiol 12:926758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Moradali MF, Ghods S, Rehm BHA (2017) Pseudomonas aeruginosa lifestyle: a paradigm for adaptation, survival, and persistence. Front Cell Infect Microbiol 7:39

    Article  PubMed  PubMed Central  Google Scholar 

  38. Hall CW, Mah T-F (2017) Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol Rev 41:276–301

    Article  CAS  PubMed  Google Scholar 

  39. Wang S, Feng Y, Han X et al (2021) Inhibition of virulence factors and biofilm formation by wogonin attenuates pathogenicity of Pseudomonas aeruginosa PAO1 via targeting pqs quorum-sensing system. Int J Mol Sci 22:12699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sarkisova S, Patrauchan MA, Berglund D et al (2005) Calcium-induced virulence factors associated with the extracellular matrix of mucoid Pseudomonas aeruginosa biofilms. J Bacteriol 187:4327–4337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Patrauchan MA, Sarkisova SA, Franklin MJ (2007) Strain-specific proteome responses of Pseudomonas aeruginosa to biofilm-associated growth and to calcium. Microbiology (N Y) 153:3838–3851

    CAS  Google Scholar 

  42. Guragain M, Lenaburg DL, Moore FS et al (2013) Calcium homeostasis in Pseudomonas aeruginosa requires multiple transporters and modulates swarming motility. Cell Calcium 54:350–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kolodkin-Gal I, Parsek MR, Patrauchan MA (2023) The roles of calcium signaling and calcium deposition in microbial multicellularity. Trends Microbiol. https://doi.org/10.1016/j.tim.2023.06.005

    Article  PubMed  Google Scholar 

  44. Wilhelm S, Tommassen J, Jaeger K-E (1999) A novel lipolytic enzyme located in the outer membrane of Pseudomonas aeruginosa. J Bacteriol 181:6977–6986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Henderson IR, Nataro JP (2001) Virulence functions of autotransporter proteins. Infect Immun 69:1231–1243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wilhelm S, Gdynia A, Tielen P et al (2007) The autotransporter esterase EstA of Pseudomonas aeruginosa is required for rhamnolipid production, cell motility, and biofilm formation. J Bacteriol 189:6695–6703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Davey ME, Caiazza NC, O’Toole GA (2003) Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1. J Bacteriol 185:1027–1036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Klausen M, Aaes-Jørgensen A, Molin S, Tolker-Nielsen T (2003) Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms. Mol Microbiol 50:61–68

    Article  CAS  PubMed  Google Scholar 

  49. Klausen M, Heydorn A, Ragas P et al (2003) Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants. Mol Microbiol 48:1511–1524

    Article  CAS  PubMed  Google Scholar 

  50. Arora SK, Neely AN, Blair B et al (2005) Role of motility and flagellin glycosylation in the pathogenesis of Pseudomonas aeruginosa burn wound infections. Infect Immun 73:4395–4398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Guo M, Gamby S, Zheng Y, Sintim H (2013) Small molecule inhibitors of AI-2 signaling in bacteria: state-of-the-art and future perspectives for anti-quorum sensing agents. Int J Mol Sci 14:17694–17728. https://doi.org/10.3390/ijms140917694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Nalca Y, Jänsch L, Bredenbruch F et al (2006) Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1: a global approach. Antimicrob Agents Chemother 50:1680–1688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mavrodi DV, Bonsall RF, Delaney SM et al (2001) Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1-carboxamide from Pseudomonas aeruginosa PAO1. J Bacteriol 183:6454–6465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hall S, McDermott C, Anoopkumar-Dukie S et al (2016) Cellular effects of pyocyanin, a secreted virulence factor of Pseudomonas aeruginosa. Toxins (Basel) 8:236

    Article  PubMed  Google Scholar 

  55. Turner JM, Messenger AJ (1986) Occurrence, biochemistry and physiology of phenazine pigment production. Adv Microb Physiol 27:211–275

    Article  CAS  PubMed  Google Scholar 

  56. Lau GW, Hassett DJ, Ran H, Kong F (2004) The role of pyocyanin in Pseudomonas aeruginosa infection. Trends Mol Med 10:599–606

    Article  CAS  PubMed  Google Scholar 

  57. Baron SS, Rowe JJ (1981) Antibiotic action of pyocyanin. Antimicrob Agents Chemother 20:814–820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. El-Mowafy SA, Abd El Galil KH, El-Messery SM, Shaaban MI (2014) Aspirin is an efficient inhibitor of quorum sensing, virulence and toxins in Pseudomonas aeruginosa. Microb Pathog 74:25–32. https://doi.org/10.1016/j.micpath.2014.07.008

    Article  CAS  PubMed  Google Scholar 

  59. Martins D, McKay G, Sampathkumar G et al (2018) Superoxide dismutase activity confers (p) ppGpp-mediated antibiotic tolerance to stationary-phase Pseudomonas aeruginosa. Proc Natl Acad Sci 115:9797–9802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Reis RS, Pereira AG, Neves BC, Freire DMG (2011) Gene regulation of rhamnolipid production in Pseudomonas aeruginosa–a review. Bioresour Technol 102:6377–6384

    Article  CAS  PubMed  Google Scholar 

  61. Jensen PØ, Bjarnsholt T, Phipps R et al (2007) Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa. Microbiology (N Y) 153:1329–1338

    CAS  Google Scholar 

  62. Deziel E, Lepine F, Milot S, Villemur R (2003) rhlA is required for the production of a novel biosurfactant promoting swarming motility in Pseudomonas aeruginosa: 3-(3-hydroxyalkanoyloxy) alkanoic acids (HAAs), the precursors of rhamnolipids. Microbiology (N Y) 149:2005–2013

    CAS  Google Scholar 

  63. Abdel-Mawgoud AM, Lépine F, Déziel E (2010) Rhamnolipids: diversity of structures, microbial origins and roles. Appl Microbiol Biotechnol 86:1323–1336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Seleem NM, Atallah H, Abd El Latif HK et al (2021) Could the analgesic drugs, paracetamol and indomethacin, function as quorum sensing inhibitors? Microb Pathog 158:105097

    Article  CAS  PubMed  Google Scholar 

  65. Kim H-S, Lee S-H, Byun Y, Park H-D (2015) 6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition. Sci Rep 5:8656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Epand RM, Walker C, Epand RF, Magarvey NA (2016) Molecular mechanisms of membrane targeting antibiotics. Biochimica et Biophysica Acta (BBA) Biomembranes 1858:980–987

    Article  CAS  PubMed  Google Scholar 

  67. Mun S-H, Kim S-B, Kong R et al (2014) Curcumin reverse methicillin resistance in Staphylococcus aureus. Molecules 19:18283–18295

    Article  PubMed  PubMed Central  Google Scholar 

  68. Wu Y, Bai J, Zhong K et al (2016) Antibacterial activity and membrane-disruptive mechanism of 3-p-trans-coumaroyl-2-hydroxyquinic acid, a novel phenolic compound from pine needles of Cedrus deodara, against Staphylococcus aureus. Molecules 21:1084

    Article  PubMed  PubMed Central  Google Scholar 

  69. Ahmed EF, El-Baky RMA, Ahmed ABF et al (2017) Antibacterial activity of some non-steroidal anti-inflammatory drugs against bacteria causing urinary tract infection. Am J Infect Dis Microbiol 5:66–73

    CAS  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the University of Rajasthan and Dr. B. Lal Institute of Biotechnology for providing technical and lab support. ADT gratefully acknowledge DBT, India for the fellowship support (DBT award no. DBT/JRF/BET-19/I/2019/AL/140). VKC gratefully acknowledges to DHR-MoHFW, Govt of India for support through Young Scientist fellowship Grant R.12014/56/2022-HR.

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Authors and Affiliations

  1. Department of Zoology, University of Rajasthan, Jaipur, Rajasthan, 302004, India

    Pooja Sharma & Bharti Chouhan

  2. Dr. B. Lal Institute of Biotechnology, University of Rajasthan, Jaipur, Rajasthan, 302017, India

    Aakanksha Kalra

  3. School of Biochemical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India

    Abhay Dev Tripathi

  4. Department of Gastroenterology, Institute of Medical Sciences (BHU), Varanasi, 221005, India

    Vivek K. Chaturvedi

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  1. Pooja Sharma
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All authors contributed to the study. PS: writing original draft, data collection, and literature search; AK: data collection, literature search, editing. ADT and VKC: editing and revision. BC: concept idea, data analysis, and revision. The final paper was reviewed and approved by all contributors.

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Correspondence to Bharti Chouhan.

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Sharma, P., Kalra, A., Tripathi, A.D. et al. Antimicrobial Proficiency of Amlodipine: Investigating its Impact on Pseudomonas spp. in Urinary Tract Infections. Indian J Microbiol (2024). https://doi.org/10.1007/s12088-024-01280-z

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