Antimicrobial activity of hydralazine against methicillin-resistant and methicillin-susceptible Staphylococcus aureus

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1. Healthcare Settings: MRSA. CDC, GA, USA (2019).
  Google Scholar
• 2. Said KB, Alghasab NS, Alharbi MSM et al. Molecular and source-specific profiling of hospital Staphylococcus aureus reveal dominance of skin infection and age-specific selections in pediatrics and geriatrics. Microorganisms. 149(17), 1–18 (2023).
  Google Scholar
• 3. Singh DK, Kapoor R, Yadav PS et al. Morbidity and mortality of necrotizing fasciitis and their prognostic factors in children. J. Indian Assoc. Pediatr. Surg. 27(5), 577 (2022).
  MedlineGoogle Scholar
• 4. Jevons MP. Methecillin resistance in staphylococci. Lancet 281(7287), 904–907 (1963).
  Google Scholar
• 5. Pulingam T, Parumasivam T, Gazzali AM et al. Antimicrobial resistance: prevalence, economic burden, mechanisms of resistance and strategies to overcome. Eur. J. Pharm. Sci. 170, 106103 (2022). •• Addresses the resistance ESKAPE pathogens.
  Medline CASGoogle Scholar
• 6. Turner NA, Sharma-Kuinkel BK, Maskarinec SA et al. Methicillin-resistant Staphylococcus aureus: an overview of basic clinical research. Nat. Rev. Microbiol. 17(4), 203–218 (2020).
  Google Scholar
• 7. Cangui-Panchi SP, Nacato-Toapanta AL, Joshu L, Reyes J, Garzon-Chavez D, Machado A. Biofilm-forming microorganisms causing hospital-acquired infections from intravenous catheter: a systematic review. Curr. Res. Microb. Sci. 3, 1–12 (2022).
  Google Scholar
• 8. Kourtis AP, Hatfield K, Baggs J et al. Vital signs: epidemiology and recent trends in methicillin-resistant and in methicillin-susceptible Staphylococcus aureus bloodstream infections – United States. MMWR 68(9), 214–219 (2020). • Data on morbidity and mortality caused by Staphylococcus aureus in the USA.
  Google Scholar
• 9. Antimicrobial Resistance in the EU/EEA (EARS-Net). Annual Epidemiological Report 2021. European Center for Diseases Prevention and Control, Stockholm, Sweden (2022).
  Google Scholar
• 10. Obeidat H, El-Nasser Z, Amarin Z, Qablan A, Gharaibeh F. The impact of COVID-19 pandemic on healthcare associated infections. Medicine 102(15), 1–5 (2023).
  Google Scholar
• 11. Garcia-Vidal C, Sanjuan G, Moreno-García E et al. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: retrospective cohort study. Clin. Microbiol. Infect. 27(1), 83–88 (2020).
  MedlineGoogle Scholar
• 12. Lai C, Chen S, Ko W, Hsueh P. Increased antimicrobial resistance during the COVID-19 pandemic. Int. J. Antimicrob. Agents 57(106324), 1–6 (2020).
  Google Scholar
• 13. Parvathaneni V, Kulkarni NS, Muth A, Gupta V. Drug repurposing: a promising tool to accelerate the drug discovery process. Drug Discov. Today 24(10), 2076–2085 (2019).
  Medline CASGoogle Scholar
• 14. Farha MA, Brown ED. Drug repurposing for antimicrobial discovery. Nat. Microbiol. 4(4), 565–577 (2019). •• The subject is the importance of drug repurposing.
  Medline CASGoogle Scholar
• 15. Shahzad Qamar A, Zamir A, Khalid S et al. A review on the clinical pharmacokinetics of hydralazine. Expert Opin. Drug Metab. Toxicol. 10(18), 707–714 (2022).
  Google Scholar
• 16. Candelaria M, Burgos S, Ponce M, Espinoza R, Dueñas-Gonzalez A. Encouraging results with the compassionate use of hydralazine/valproate (TRANSKRIP™) as epigenetic treatment for myelodysplastic syndrome (MDS). Ann. Hematol. 96(11), 1825–1832 (2017). •• Repurposing hydralazine.
  Medline CASGoogle Scholar
• 17. Lopes N, Pacheco MB, Soares-Fernandes D et al. Hydralazine and enzalutamide: synergistic partners against prostate cancer. Biomedicines 9(8), 976 (2021).
  Medline CASGoogle Scholar
• 18. Vázquez AA, Torres FC, Ramírez BS et al. Cell-type dependent regulation of pluripotency and chromatin remodeling genes by hydralazine. Stem Cell Res. Ther. 14(42), 1–14 (2023).
  MedlineGoogle Scholar
• 19. Ramesha KP, Mohana NC, Nayaka SC, Satish S. Epigenetic modifiers revamp secondary metabolite production in endophytic Nigrospora sphaerica. 12(730355), 1–8 (2021).
  Google Scholar
• 20. Mistry S, Singh AK. Synthesis and in vitro antimicrobial activity of new steroidal hydrazone derivatives. Future J. Pharm. Sci. 8(7), 10 (2022).
  Google Scholar
• 21. Awantu AF, Fongang YSF, Ayimele GA et al. Novel hydralazine Schiff base derivatives and their antimicrobial, antioxidant and antiplasmodial properties. Int. J. Organ. Chem. 10(1), 1–16 (2020).
  CASGoogle Scholar
• 22. Clinical and Laboratory Standards Institute. Broth microdilution method. In: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically (10th Edition): Approved Standard M07-A10 (2015).
  Google Scholar
• 23. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing Supplement M100S (26th Edition). (2016).
  Google Scholar
• 24. Das B, Mandal D, Dash SK et al. Eugenol provokes ROS-mediated membrane damage-associated antibacterial activity against clinically isolated multidrug-resistant Staphylococcus aureus strains. Infect. Dis. Res. Treat. 9, 11–19 (2016).
  Google Scholar
• 25. Odds FC. Synergy, antagonism, and what the chequerboard puts between them. J. Antimicrob. Chemother. 52(1), 1 (2003).
  Medline CASGoogle Scholar
• 26. Jorge P, Grzywacz D, Kamysz W, Lourenço A, Pereira MO. Searching for new strategies against biofilm infections: colistin-AMP combinations against Pseudomonas aeruginosa and Staphylococcus aureus single- and double-species biofilms. PLoS One 12(3), 1–20 (2017).
  Google Scholar
• 27. Stepanović S, Vuković D, Dakić I, Savić B, Švabić-Vlahović M. A modified microtiter-plate test for quantification of staphylococcal biofilm formation. J. Microbiol. Methods 40(2), 175–179 (2000).
  Medline CASGoogle Scholar
• 28. Costa EM, Silva S, Madureira AR, Cardelle-Cobas A, Tavaria FK, Pintado MM. A comprehensive study into the impact of a chitosan mouthwash upon oral microorganism's biofilm formation in vitro. Carbohydr. Polym. 101(1), 1081–1086 (2014).
  Medline CASGoogle Scholar
• 29. Queiroz HA, da Silva CR, de Andrade Neto JB et al. Synergistic activity of diclofenac sodium with oxacillin against planktonic cells and biofilm of methicillin-resistant Staphylococcus aureus strains. Future Microbiol. 16(6), 375–387 (2021).
  CASGoogle Scholar
• 30. Neto JBA, da Silva CR, Nascimento FBSA et al. Screening of antimicrobial metabolite yeast isolates derived biome Ceará against pathogenic bacteria, including MRSA: antibacterial activity and mode of action evaluated by flow cytometry. Int. J. Curr. Microbiol. App. Sci. 4(5), 459–472 (2015).
  CASGoogle Scholar
• 31. Dwyer DJ, Camacho DM, Kohanski MA, Callura JM. Antibiotic-induced bacterial cell death exhibits physiological and biochemical hallmarks of apoptosis. Mol. Cell. 46(5), 561–572 (2012).
  Medline CASGoogle Scholar
• 32. Miloshev G, Mihaylov I, Anachkova B. Application of the single cell gel electrophoresis on yeast cells. 513(8), 69–74 (2002).
  Google Scholar
• 33. Cavalcanti BC, Bezerra DP, Magalhães HIF et al. Kauren-19-oic acid induces DNA damage followed by apoptosis in human leukemia cells. J. Appl. Toxicol. 29(7), 560–568 (2009).
  Medline CASGoogle Scholar
• 34. Csizmadia P. MarvinSketch and MarvinView: molecule applets for the World Wide Web. Proceedings of The 3rdInternational Electronic Conference on Synthetic Organic Chemistry. 1–30 (1999).
  Google Scholar
• 35. Hanwell MD, Curtis DE, Lonie DC, Vandermeerschd T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Cheminform. 4(17), 1–33 (2012).
  MedlineGoogle Scholar
• 36. Halgren TA. Merck Molecular Force Field I. Basis, form, scope, parameterization, and performance of MMFF94. J. Comput. Chem. 17(5), 490–519 (1996).
  CASGoogle Scholar
• 37. Batista de Andrade Neto J, Pessoa de Farias Cabral V, Brito Nogueira LF et al. Anti-MRSA activity of curcumin in planktonic cells and biofilms and determination of possible action mechanisms. Microb. Pathog. 155(104892), 1–9 (2021).
  Google Scholar
• 38. Yan J, Zhang G, Pan J, Wang Y. α-Glucosidase inhibition by luteolin: kinetics, interaction and molecular docking. Int. J. Biol. Macromol. 64, 213–223 (2014).
  Medline CASGoogle Scholar
• 39. Huey R, Morris GM, Forli S. Using AutoDock 4 and AutoDock Vina with AutoDockTools: a tutorial. Scripps Res. Inst. Mol. 32(12), 1–32 (2012).
  Google Scholar
• 40. Fujita J, Maeda Y, Nagao C et al. Crystal structure of FtsA from Staphylococcus aureus. FEBS Lett. 588(10), 1879–1885 (2014).
  Medline CASGoogle Scholar
• 41. Heaslet H, Harris M, Fahnoe K et al. Structural comparison of chromosomal and exogenous dihydrofolate reductase from Staphylococcus aureus in complex with the potent inhibitor trimethoprim. Proteins Struct. Funct. Bioinforma. 76(3), 706–717 (2009).
  Medline CASGoogle Scholar
• 42. Bax BD, Chan PF, Eggleston DS et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature 466(7309), 935–940 (2010).
  MedlineGoogle Scholar
• 43. Singh SB, Kaelin DE, Wu J et al. Tricyclic 1,5-naphthyridinone oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents-SAR of left-hand-side moiety (Part-2). Bioorganic Med. Chem. Lett. 25(9), 1831–1835 (2015).
  Medline CASGoogle Scholar
• 44. Neidle S, Mann J, Rayner EL et al. Symmetric bis-benzimidazoles: new sequence-selective DNA-binding molecules. Chem. Comm. 30(37), 929–930 (1999).
  Google Scholar
• 45. Liu C, Liu GY, Song Y et al. Cholesterol biosynthesis inhibitor Blocks Staphylococcus aureus virulence. Science 319(5868), 1391–1394 (2009).
  Google Scholar
• 46. Nguyen T, Kim T, Ta HM et al. Targeting mannitol metabolism as an alternative antimicrobial strategy based on the structure–function study of mannitol-1-phosphate dehydrogenase in Staphylococcus aureus. MBio 10(4), 1–23 (2019).
  Google Scholar
• 47. Guillet V, Roblin P, Werner S et al. Crystal structure of leucotoxin S component: new insight into the staphylococcal β-barrel pore-forming toxins. J. Biol. Chem. 279(39), 41028–41037 (2004).
  Medline CASGoogle Scholar
• 48. Foletti D, Strop P, Shaughnessy L et al. Mechanism of action and in vivo efficacy of a human-derived antibody against Staphylococcus aureus α-hemolysin. J. Mol. Biol. 425(10), 1641–1654 (2013).
  Medline CASGoogle Scholar
• 49. Otero LH, Rojas-Altuve A, Llarrull LI et al. How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function. Proc. Natl Acad. Sci. U. S. A. 110(42), 16808–16813 (2013).
  MedlineGoogle Scholar
• 50. Qiu X, Janson CA, Smith WW et al. Crystal structure of Staphylococcus aureus tyrosyl-tRNA synthetase in complex with a class of potent and specific inhibitors. 10(10), 1925–2139 (2001).
  Google Scholar
• 51. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31(2), 455–461 (2009).
  Google Scholar
• 52. Marinho EM, Batista de Andrade Neto J, Silva J et al. Virtual screening based on molecular docking of possible inhibitors of COVID-19 main protease. Microb. Pathog. 148(6), 1–6 (2020).
  Google Scholar
• 53. Yusuf D, Davis AM, Kleywegt GJ, Schmitt S. An alternative method for the evaluation of docking performance: RSR vs RMSD. J. Chem. Inf. Model. 48(7), 1411–1422 (2008).
  Medline CASGoogle Scholar
• 54. Shityakov S, Förster C. In silico predictive model to determine vector-mediated transport properties for the blood–brain barrier choline transporter. Adv. Appl. Bioinforma. Chem. 7(1), 23–36 (2014).
  MedlineGoogle Scholar
• 55. Silva J, da Rocha MN, Marinho EM, Marinho MM, Marinho ES, dos Santos HS. Evaluation of the ADME, toxicological analysis and molecular docking studies of the anacardic acid derivatives with potential antibacterial effects against Staphylococcus aureus. J. Anal. Pharm. Res. 10(5), 177–194 (2021).
  Google Scholar
• 56. Pettersen EF, Goddard TD, Huang CC et al. UCSF chimera – a visualization system for exploratory research and analysis. J. Comput. Chem. 25(13), 1605–1612 (2004).
  Medline CASGoogle Scholar
• 57. Kadela-Tomanek M, Jastrzębska M, Marciniec K, Chrobak E, Bębenek E, Boryczka S. Lipophilicity, pharmacokinetic properties, and molecular docking study on SARS-CoV-2 target for betulin triazole derivatives with attached 1,4-quinone. Pharmaceutics 13(6), 781-802 (2021).
  MedlineGoogle Scholar
• 58. Imberty A, Hardman KD, Carver JP, Perez S. Molecular modelling of protein–carbohydrate interactions. Docking of monosaccharides in the binding site of concanavalin A. Glycobiology 1(6), 631–642 (1991).
  Medline CASGoogle Scholar
• 59. Diekema DJ, Hsueh P, Mendes RE et al. The microbiology of bloodstream infection: 20-year trends from the SENTRY antimicrobial surveillance program. 63(7), 1–10 (2019).
  Google Scholar
• 60. Cassol R, Falci DR, Ramirez M. Epidemiology and risk factors for mortality among methicillin-resistant Staphylococcus aureus bacteremic patients in southern Brazil. 13(4), 1–9 (2023).
  Google Scholar
• 61. Liu Y, Tong Z, Shi J, Li R, Upton M, Wang Z. Drug repurposing for next-generation combination therapies against multidrug-resistant bacteria. Theranostics 11(10), 4910–4928 (2021). •• Addresses the issue of bacterial resistance and drug repurposing.
  Medline CASGoogle Scholar
• 62. Bauman J, Shaheen M, Verschraegen CF, Belinsky SA. A phase I protocol of hydralazine and valproic acid in advanced, previously treated solid cancers. Transl. Oncol. 7(3), 349–354 (2014).
  MedlineGoogle Scholar
• 63. Candelaria M, Gallardo-Rincón D, Arce C et al. A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors. Ann. Oncol. 18(9), 1529–1538 (2007).
  Medline CASGoogle Scholar
• 64. Michki NS, Ndeh R, Helmin KA, Singer BD, Morrow SAM. DNA methyltransferase inhibition induces dynamic gene expression changes in lung – CD₄⁺ T cells pneumonia. Sci. Rep. 13(4283), 1–11 (2023).
  MedlineGoogle Scholar
• 65. Lopez M, Gilbert J, Contreras J, Halby L, Arimondo PB. Inhibitors of DNA Methylation. DNA Methyltransferases - Role and Function. 1398, 471–513 (2022).
  Google Scholar
• 66. do Nascimento FB, Valente Sá LG, de Andrade Neto JB et al. Synergistic effect of hydralazine associated with triazoles on Candida spp. in planktonic cells. Future Microbiol. 18, 661–672 (2023).
  CASGoogle Scholar
• 67. Morales G, Paredes A, Sierra P, Loyola LA. Antimicrobial activity of three baccharis species used in the traditional medicine of northern Chile. Molecules 13(4), 790–794 (2008).
  Medline CASGoogle Scholar
• 68. Josino MAA, Rocha da Silva C, de Andrade Neto JB et al. Development and in vitro evaluation of microparticles of fluoxetine in galactomannan against biofilms of S. aureus methicilin resistant. Carbohydr. Polym. 252(117184), 1–7 (2021).
  Google Scholar
• 69. Av Sá LGD, Silva CRD, de Andrade Neto JB et al. Etomidate inhibits the growth of MRSA and exhibits synergism with oxacillin. Future Microbiol. 15(17), 1611–1619 (2020).
  Google Scholar
• 70. Saha I, Ghosh N, Plewczynski D et al. Identification of human miRNA biomarkers targeting the SARS-CoV-2 genome. ACS Omega 7(50), 46411–46420 (2022).
  Medline CASGoogle Scholar
• 71. Ranjan K, Brandão F, Morais JAV et al. The role of Cryptococcus neoformans histone deacetylase genes in the response to antifungal drugs, epigenetic modulators and to photodynamic therapy mediated by an aluminium phthalocyanine chloride nanoemulsion in vitro. J. Photochem. Photobiol. B. Biol. 216(112131), 1–13 (2021).
  Google Scholar
• 72. Coronel J, Cetina L, Pacheco I, Perez-Cardenas EDCE, Gonza A, Duen A. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results. Med. Oncol. 28, 540–546 (2011).
  CASGoogle Scholar
• 73. Li M, Yu J, Guo G, Shen H. Interactions between macrophages and biofilm during Staphylococcus aureus-associated implant infection: difficulties and solutions. J Innate Immun. 15(1), 499–515 (2023).
  Medline CASGoogle Scholar
• 74. Liu Y, Zhang J, Ji Y. Environmental factors modulate biofilm formation by Staphylococcus aureus. Sci. Prog. 103(1), 1–14 (2020).
  Google Scholar
• 75. Mahdally NH, George RF, Kashef MT, Al-Ghobashy M, Murad FE, Attia AS. Staquorsin: a novel Staphylococcus aureus Agr-mediated quorum sensing inhibitor impairing virulence in vivo without notable resistance development. Front. Microbiol. 12, 1–12 (2021).
  Google Scholar
• 76. Marutescu LG. Current and future flow cytometry applications contributing to antimicrobial resistance control. Microorganisms 11(5), 1–17 (2023).
  Google Scholar
• 77. Batista de Andrade Neto J, Alexandre Josino MA, Rocha da Silva C et al. A mechanistic approach to the in-vitro resistance modulating effects of fluoxetine against meticillin resistant Staphylococcus aureus strains. Microb. Pathog. 127, 335–340 (2019).
  MedlineGoogle Scholar
• 78. Bayles KW. Making sense of a paradox. Nat. Publ. Gr. 12(1), 63–69 (2014). •• Addresses the complexity of bacterial cell death.
  CASGoogle Scholar
• 79. Melton D, Lewis CD, Price NE, Gates KS. Covalent adduct formation between the antihypertensive drug hydralazine and abasic sites in double- and single-stranded DNA. Chem. Res. Toxicol. 27(12), 2113–2118 (2014). •• Authors show that the genotic properties of hydralazine possibly occur due to endogenous DNA damage.
  Medline CASGoogle Scholar
• 80. Collin F, Karkare S, Maxwell A. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl. Microbiol. Biotechnol. 92(3), 479–497 (2011).
  Medline CASGoogle Scholar
• 81. Heddle J, Maxwell A. Quinolone-binding pocket of DNA gyrase: role of GyrB. Antimicrob Agents Chemother. 46(6), 1805–1815 (2002).
  Medline CASGoogle Scholar
• 82. Spencer AC, Panda SS. DNA gyrase as a target for quinolones. Biomedicines 11(371), 1–27 (2023). •• Addresses the drugs acting on DNA gyrase.
  Google Scholar
• 83. Lahiri SD, Kutschke A, McCormack K, Alm RA. Insights into the mechanism of inhibition of novel bacteria topoisomerase inhibitors from characterization of resistant mutants of Staphylococcus aureus. Antimicrob. Agents Chemother. 59(9), 5278–5287 (2015).
  Medline CASGoogle Scholar
• 84. Mlynarczyk-Bonikowska B, Kowalewski C, Krolak-Ulinska A, Marusza W. Molecular mechanisms of drug resistance in Staphylococcus aureus. Int J Mol Sci. 23(15), 8088–8121 (2022).
  Medline CASGoogle Scholar
• 85. Brick P, Blow DM. Crystal structure of a deletion mutant of a tyrosyl-tRNA synthetase complexed with tyrosine. J Mol Biol. 194(2), 287–289 (1987).
  Medline CASGoogle Scholar
• 86. Bedouelle H. Tyrosyl-tRNA synthetases. Madame Curie Bioscience Database (2013).
  Google Scholar