Computational and Experimental Drug Discovery Targeting the Glycolytic Pathway in Methicillin-Resistant Staphylococcus Aureus

Authors

  • Ziyao Liu School of biochemistry, University of Edinburgh, Edinburgh, UK Author

DOI:

https://doi.org/10.71222/s0kt8x87

Keywords:

drug discovery, methicillin-resistant Staphylococcus aureus, fructose-1, 6-bisphosphate aldolase, molecular docking, enzymatic assays, active site binding

Abstract

This dissertation studies the metabolic pathways of methicillin-resistant Staphylococcus aureus (MRSA), focusing on the enzyme MRSaFBA. It highlights the enzyme's potential as a therapeutic target for antibacterial strategies. By employing biophysical techniques including Dynamic Light Scattering (DLS) and Thermal Denaturation Analysis (TDA), the study provides new insights into the structural stability and aggregation behavior of MRSaFBA under various conditions. The research also demonstrates improvements in protein production and purification processes, enhancing the yield and purity of MRSaFBA and enabling more precise biochemical characterization. Furthermore, enzymatic assays confirm the enzyme's sensitivity to environmental factors and inhibitors, underscoring its potential as a drug target. The study also incorporates molecular docking to understand the interaction mechanisms of potential inhibitors, laying a foundation for the development of MRSaFBA-HCA site.

References

1. H. F. Wertheim, D. C. Melles, M. C. Vos, et al., “The role of nasal carriage in Staphylococcus aureus infections,” Lancet Infect. Dis., vol. 5, no. 12, pp. 751–762, 2005, doi: 10.1016/S1473-3099(05)70255-4.

2. D. J. Diekema, M. A. Pfaller, F. J. Schmitz, et al., “Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997–1999,” Clin. Infect. Dis., vol. 32 Suppl 2, pp. S114–S132, 2001, doi: 10.1086/323274.

3. A. S. Lee, H. de Lencastre, J. Garau, et al., “Methicillin-resistant Staphylococcus aureus,” Nat. Rev. Dis. Primers, vol. 4, p. 18033, 2018, doi: 10.1038/s41572-018-0033-8.

4. F. D. Lowy, “Staphylococcus aureus infections,” N. Engl. J. Med., vol. 339, no. 8, pp. 520–532, 1998, doi: 10.1056/NEJM199808203390806.

5. S. A. Anuj, H. P. Gajera, D. G. Hirpara, et al., “Interruption in membrane permeability of drug-resistant Staphylococcus aureus with cationic particles of nano-silver,” Eur. J. Pharm. Sci., vol. 127, pp. 208–216, 2019, doi: 10.1056/NEJM199808203390806.

6. S. G. Zárate, P. Morales, K. Świderek, et al., “A molecular modeling approach to identify novel inhibitors of the major facilitator superfamily of efflux pump transporters,” Antibiotics, vol. 8, no. 1, p. 13, 2019, doi: 10.1016/j.ejps.2018.12.014.

7. T. Matono, M. Nagashima, K. Mezaki, et al., “Molecular epidemiology of β-lactamase production in penicillin-susceptible Staphylococcus aureus under high-susceptibility conditions,” J. Infect. Chemother., vol. 24, no. 2, pp. 153–155, 2018, doi: 10.3390/antibiotics8010001.

8. L. Kime, C. P. Randall, F. I. Banda, et al., “Transient silencing of antibiotic resistance by mutation represents a significant po-tential source of unanticipated therapeutic failure,” mBio, vol. 10, no. 5, pp. 1–13, 2019, doi: 10.1016/j.jiac.2017.11.005.

9. R. Kanwari, A. K. Sah, and P. Suresh, “Biofilm-mediated antibiotic-resistant oral bacterial infection,” Curr. Drug Targets, doi: 10.2174/1381612822666161124154549.

10. A. F. Haag, J. R. Fitzgerald, J. R. Penadés, et al., “Staphylococcus aureus in animals,” Microbiol. Spectr., vol. 7, no. 3, p. GPP3-0060-2019, 2019, doi: 10.1128/microbiolspec.GPP3-0060-2019.

11. A. Fetsch and S. Johler, “Staphylococcus aureus as a foodborne pathogen,” Curr. Clin. Microbiol. Rep., vol. 5, no. 2, pp. 88–96, 2018, doi: 10.1007/s40588-018-0111-2.

12. B. Sancak, “Staphylococcus aureus and antibiotic resistance,” Mikrobiyol. Bul., vol. 45, no. 3, pp. 565–576, 2011, doi: 10.5402/2011/812049.

13. D. Lim and N. C. Strynadka, “Structural basis for the β-lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus,” Nat. Struct. Biol., vol. 9, no. 11, pp. 870–876, 2002, doi: 10.1038/nsb813.

14. K. A. Lacey, J. A. Geoghegan, and R. M. McLoughlin, “The role of Staphylococcus aureus virulence factors in skin infection and their potential as vaccine antigens,” Pathogens, vol. 5, no. 1, p. 22, 2016, doi: 10.3390/pathogens5010022.

15. L. Tuchscherr, B. Löffler, and R. A. Proctor, “Persistence of Staphylococcus aureus: multiple metabolic pathways impact the expression of virulence factors in small-colony variants (SCVs),” Front. Microbiol., vol. 11, p. 1028, 2020, doi: 10.3389/fmicb.2020.01028.

16. A. E. Paharik and A. R. Horswill, “The staphylococcal biofilm: adhesins, regulation, and host response,” Microbiol. Spectr., vol. 4, no. 2, p. VMBF-0022-2015, 2016, doi: 10.1128/microbiolspec.VMBF-0022-2015.

17. R. M. Donlan, “Biofilms: microbial life on surfaces,” Emerg. Infect. Dis., vol. 8, no. 9, p. 881, 2002, doi: 10.3201/eid0809.020063.

18. G. Y. C. Cheung, J. S. Bae, and M. Otto, “Pathogenicity and virulence of Staphylococcus aureus,” Virulence, vol. 12, no. 1, pp. 547–569, 2021, doi: 10.1080/21505594.2020.1839562.

19. K. Tam, V. J. Torres, V. A. Fischetti, et al., “Staphylococcus aureus secreted toxins and extracellular enzymes,” Microbiol. Spectr., vol. 7, no. 2, p. GPP3-0039-2018, 2019, doi: 10.1128/microbiolspec.GPP3-0039-2018.

20. S. Divyakolu, R. Chikkala, K. S. Ratnakar, et al., “Hemolysins of Staphylococcus aureus—an update on their biology, role in pathogenesis and as targets for antivirulence therapy,” Adv. Infect. Dis., vol. 9, no. 2, pp. 80–104, 2019, doi: 10.1155/2019/6483049.

21. C. Liu, Y. Shen, M. Yang, et al., “Hazard of staphylococcal enterotoxins in food and promising strategies for natural products against virulence,” J. Agric. Food Chem., vol. 70, no. 8, pp. 2450–2465, 2022, doi: 10.1021/acs.jafc.1c07141.

22. J. K. McCormick, J. M. Yarwood, and P. M. Schlievert, “Toxic shock syndrome and bacterial superantigens: an update,” Annu. Rev. Microbiol., vol. 55, no. 1, pp. 77–104, 2001, doi: 10.1146/annurev.micro.55.1.77.

23. A. Sakr, F. Bregeon, J.-L. Mege, et al., “Staphylococcus aureus nasal colonization: an update on mechanisms, epidemiology, risk factors, and subsequent infections,” Front. Microbiol., vol. 9, p. 2419, 2018, doi: 10.3389/fmicb.2018.02419.

24. L. G. Bode, J. A. Kluytmans, H. F. Wertheim, et al., “Preventing surgical-site infections in nasal carriers of Staphylococcus aureus,” N. Engl. J. Med., vol. 362, no. 1, pp. 9–17, 2010, doi: 10.1056/NEJMoa0808939.

25. H. Dixit, M. Kulharia, and S. K. Verma, “Metal-binding proteins and proteases in RNA viruses: unravelling functional diversity and expanding therapeutic horizons,” J. Virol., vol. 97, no. 12, e0139923, Dec. 2023, doi: 10.1128/jvi.01399-23.

26. S. S. Huang, R. Singh, J. A. McKinnell, et al., “Decolonization to reduce postdischarge infection risk among MRSA carriers,” N. Engl. J. Med., vol. 380, no. 7, pp. 638–650, 2019, doi: 10.1056/NEJMoa1810913.

27. A. Hamdan-Partida, S. Gonzalez-Garcia, E. de la Rosa Garcia, et al., “Community acquired methicillin-resistant Staphylococcus aureus can persist in the throat,” Int. J. Med. Microbiol., vol. 308, no. 4, pp. 469–475, 2018, doi: 10.1016/j.ijmm.2018.04.002.

28. I. S. Petersen, P. L. Larsen, B. L. Brandelev, et al., “Close association between oropharyngeal and rhinopharyngeal colonization with Staphylococcus aureus – clues to new insight of MRSA colonization of the oropharynx,” J. Hosp. Infect., vol. 84, no. 3, pp. 259–262, 2013, doi: 10.1016/j.jhin.2013.04.007.

29. E. S. Yang, J. Tan, S. Eells, et al., “Body site colonization in patients with community-associated methicillin-resistant Staphylo-coccus aureus and other types of S. aureus skin infections,” Clin. Microbiol. Infect., vol. 16, no. 5, pp. 425–431, 2010, doi: 10.1111/j.1469-0691.2009.02836.

30. D. S. Acton, M. J. Tempelmans Plat-Sinnige, W. van Wamel, et al., “Intestinal carriage of Staphylococcus aureus: how does its frequency compare with that of nasal carriage and what is its clinical impact?” Eur. J. Clin. Microbiol. Infect. Dis., vol. 28, no. 2, p. 115, 2008, doi: 10.1007/s10096-007-0384-6.

31. D. M. Gries, N. J. Pultz, and C. J. Donskey, “Growth in cecal mucus facilitates colonization of the mouse intestinal tract by methicillin-resistant Staphylococcus aureus,” J. Infect. Dis., vol. 192, no. 9, pp. 1621–1627, 2005, doi: 10.1086/430464.

32. T. S. Lo and S. M. Borchardt, “Antibiotic-associated diarrhea due to methicillin resistant Staphylococcus aureus,” Diagn. Microbiol. Infect. Dis., vol. 63, no. 4, pp. 388–389, 2009, doi: 10.1016/j.diagmicrobio.2008.12.007.

33. M. Y. Khan and W. H. Hall, “Staphylococcal enterocolitis—treatment with oral vancomycin,” Ann. Intern. Med., vol. 65, no. 1, pp. 1–8, 1966, doi: 10.7326/0003-4819-65-1-1.

34. M. A. Krezalek, S. Hyoju, A. Zaborin, et al., “Can methicillin-resistant Staphylococcus aureus silently travel from the gut to the wound and cause postoperative infection? Modeling the ‘Trojan Horse Hypothesis’,” Ann. Surg., vol. 267, no. 4, pp. 749–758, 2018, doi: 10.1097/SLA.0000000000002173.

35. E. J. Raineri, D. Altulea, and J. M. van Dijl, “Staphylococcal trafficking and infection—from ‘nose to gut’ and back,” FEMS Microbiol. Rev., vol. 46, no. 1, p. fuab041, 2021, doi: 10.1093/femsre/fuab041.

36. C.-J. Yao, Y.-L. Li, M.-J. Pu, et al., “Aminoglycosides with anti-MRSA activity: a concise review,” Curr. Top. Med. Chem., vol. 21, no. 27, pp. 2483–2499, 2021, doi: 10.2174/1568026621666211004093647.

37. T. Yamamichi, M. Yoshida, T. Sakai, et al., “Factors associated with neonatal surgical site infection after abdominal surgery,” Pediatr. Surg. Int., vol. 38, no. 2, pp. 317–323, 2022, doi: 10.1007/s00383-021-05051-5.

38. C.-M. Yueh, H. Chi, N.-C. Chiu, et al., “Etiology, clinical features, management, and outcomes of skin and soft tissue infections in hospitalized children: A 10-year review,” J. Microbiol. Immunol. Infect., vol. 55, no. 4, pp. 728–739, 2022, doi: 10.1016/j.jmii.2022.01.007.

39. S. Alosaimy, N. L. Sabagha, A. M. Lagnf, et al., “Monotherapy with vancomycin or daptomycin versus combination therapy with beta-lactams in the treatment of methicillin-resistant Staphylococcus aureus bloodstream infections: a retrospective cohort analysis,” Infect. Dis. Ther., vol. 9, no. 2, pp. 325–339, 2020, doi: 10.1007/s40121-020-00292-8.

40. W. Abebe, B. Tegene, T. Feleke, et al., “Bacterial bloodstream infections and their antimicrobial susceptibility patterns in chil-dren and adults in Ethiopia: a 6-year retrospective study,” Clin. Lab., vol. 67, no. 11, pp. 2453–2461, 2021, doi: 10.7754/Clin.Lab.2021.210224.

41. S. Arakawa, M. Kasai, S. Kawai, et al., “The JAID/JSC guidelines for management of infectious diseases 2017—Sepsis and catheter-related bloodstream infection,” J. Infect. Chemother., vol. 27, no. 5, pp. 657–677, 2021, doi: 10.1016/j.jiac.2019.11.011.

42. M. Anvarinejad, M. Khalifeh, J. Mardaneh, et al., “Bloodstream infections in the south of Iran: microbiological profile and an-tibiotic-resistance patterns of isolated bacteria,” Crescent J. Med. Biol. Sci., vol. 8, no. 4, pp. 312–318, 2021.

43. V. Agrawal, A. T. Valson, Y. D. Bakthavatchalam, et al., “Skin colonizers and catheter associated blood stream infections in incident Indian dialysis patients,” Indian J. Nephrol., vol. 32, no. 1, pp. 34–41, 2022, doi: 10.4103/ijn.IJN_400_20.

44. S.-S. Jean, Y.-C. Chang, W.-C. Lin, et al., “Epidemiology, treatment, and prevention of nosocomial bacterial pneumonia,” J. Clin. Med., vol. 9, no. 1, p. 275, 2020, doi: 10.3390/jcm9010275.

45. M. S. Soliman, N. S. Soliman, A. R. El-Manakhly, et al., “Genomic characterization of methicillin-resistant Staphylococcus aureus (MRSA) by high-throughput sequencing in a tertiary care hospital,” Genes, vol. 11, no. 10, p. 1219, 2020, doi: 10.3390/genes11101219.

46. M. Ohlmeier, S. Filitarin, G. Delgado, et al., “Improved treatment strategies can result in better outcomes following one-stage exchange surgery for MRSA periprosthetic joint infection,” J. Med. Microbiol., vol. 69, no. 8, 2020, doi: 10.1099/jmm.0.001229.

47. A. Ou, K. Wang, Y. Mao, et al., “First report on the rapid detection and identification of methicillin-resistant Staphylococcus aureus (MRSA) in viable but non-culturable (VBNC) under food storage conditions,” Front. Microbiol., vol. 11, 2021, doi: 10.3389/fmicb.2020.615875.

48. A. Alabresm, Y. P. Chen, S. Wichter-Chandler, et al., “Nanoparticles as antibiotic-delivery vehicles (ADVs) overcome resistance by MRSA and other MDR bacterial pathogens: The grenade hypothesis,” J. Glob. Antimicrob. Resist., vol. 22, 2020, doi: 10.1016/j.jgar.2020.06.023.

49. G. Gagandeep, P. Kumar, S. K. Kandi, et al., “Synthesis of novel monocarbonyl curcuminoids, evaluation of their efficacy against MRSA, including ex vivo infection model and their mechanistic studies,” Eur. J. Med. Chem., vol. 195, p. 112276, 2020, doi: 10.1016/j.ejmech.2020.112276.

50. G. K. Paterson, “Low prevalence of livestock associated methicillin-resistant Staphylococcus aureus clonal complex 398 and mecC MRSA among human isolates in Northeast England,” J. Appl. Microbiol., vol. 128, no. 6, 2020, doi: 10.1111/jam.14578.

51. Y. Qiao, X. Liu, B. Li, et al., “Treatment of MRSA-infected osteomyelitis using bacterial capturing, magnetically targeted composites with microwave-assisted bacterial killing,” Nat. Commun., vol. 11, no. 1, p. 4446, 2020, doi: 10.1038/s41467-020-18271-4.

52. B. T. M. J. A., B. K. C. M. A., B. M. A. M. A., et al., “Combination ceftaroline and daptomycin salvage therapy for complicated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia compared with standard of care,” Int. J. Antimicrob. Agents, 2021, doi: 10.1016/j.ijantimicag.2021.106310.

53. D. C. Coleman, A. C. Shore, R. V. Goering, et al., “New insights and updates on the molecular epidemiology and antimicrobial resistance of MRSA in humans in the whole genome sequencing era,” Front. Microbiol., vol. 10, 2019, p. 637, doi: 10.3389/fmicb.2019.00637.

54. S. H. Kuo, C. S. Chien, C. C. Wang, et al., “Antibacterial activity of BSA-capped gold nanoclusters against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin intermediate Staphylococcus aureus (VISA),” J. Nanomater., vol. 2019, pp. 1–7, 2019, doi:.

55. S.-C. Yang, K.-W. Shih, et al., “Discovery of furanoquinone derivatives as a novel class of DNA polymerase and gyrase inhib-itors for MRSA eradication in cutaneous infection,” Front. Microbiol., vol. 10, p. 1197, 2019, doi: 10.3389/fmicb.2019.01197.

56. G.-Y. Zuo, C.-X. Cui, et al., “Potent anti-MRSA activity and synergism with aminoglycosides by flavonoid derivatives from the root barks of Morus alba, a traditional Chinese medicine,” Med. Chem. Res., vol. 28, no. 9, pp. 1547–1556, 2019, doi: 10.1007/s00044-019-02393-7.

57. B. Chen, “Molecular mechanism of HIV-1 entry,” Trends Microbiol., vol. 27, no. 10, pp. 878–891, 2019, doi: 10.1016/j.tim.2019.06.002.

58. M. R. S. A. Janjua, “Structure–property relationship and systematic study of a series of terpyridine-based nonlinear optical compounds: DFT computation of interactive design,” J. Cluster Sci., vol. 30, no. 1, pp. 45–51, 2019, doi: 10.1007/s10876-018-1445-6.

59. C. D. de Morais Oliveira-Tintino, S. R. Tintino, D. F. Muniz, et al., “Do 1,8 naphthyridine sulfonamides possess an inhibitory action against TetK and MrsA efflux pumps in multiresistant Staphylococcus aureus strains?” Microb. Pathog., vol. 147, p. 104268, 2020, doi: 10.1016/j.micpath.2020.104268.

60. J. K. Ferguson, S. A. Munnoch, K. Kozierowski, et al., “Reduced VRE and MRSA colonisation and infection following sustained reduction in broad spectrum antibiotic use in a large tertiary hospital,” Med. J. Aust., vol. 211, no. 3, 2019, doi: 10.5694/mja2.50218.

61. F. Gu, W. He, S. Xiao, et al., “Antimicrobial resistance and molecular epidemiology of Staphylococcus aureus causing blood-stream infections at Ruijin Hospital in Shanghai from 2013 to 2018,” Sci. Rep., vol. 10, no. 1, 2020, doi: 10.1038/s41598-020-62444-1.

62. Yao, Chen, Yuan, et al., “Design, synthesis, and antibacterial evaluation of novel derivatives of NPS-2143 for the treatment of methicillin-resistant S. aureus (MRSA) infection,” J. Antibiotics, 2019, doi: 10.1038/s41429-019-0177-9.

63. Y. W. Chang, W. C. Huang, C. Y. Lin, et al., “Tellimagrandin II, a type of plant polyphenol extracted from Trapa bispinosa inhibits antibiotic resistance of drug-resistant Staphylococcus aureus,” Int. J. Mol. Sci., vol. 20, no. 22, 2019, doi: 10.3390/ijms20225666.

64. A. Alberto, T. G. Tommaso, M. C. Marco, et al., “Staphylococcus aureus from hospital-acquired pneumonia from an Italian nationwide survey: Activity of ceftobiprole and other anti-staphylococcal agents, and molecular epidemiology of methicil-lin-resistant isolates,” J. Antimicrob. Chemother., no. 12, 2019, doi: 10.1093/jac/dkz371.

65. B. K. G. Eriksson, U.-B. Thollström, J. Nederby-Öhd, et al., “Epidemiology and control of meticillin-resistant Staphylococcus aureus in Stockholm County, Sweden, 2000 to 2016: Overview of a 'search-and-contain' strategy,” Eur. J. Clin. Microbiol. Infect. Dis., vol. 38, no. 12, pp. 2221–2228, 2019, doi: 10.1007/s10096-019-03622-6.

66. K. O. Kwok, E. Chan, P. H. Chung, et al., “Prevalence and associated factors for carriage of Enterobacteriaceae producing ESBLs or carbapenemase and methicillin-resistant Staphylococcus aureus in Hong Kong community,” J. Infect., vol. 81, no. 2, pp. 242-247, 2020, doi: 10.1016/j.jinf.2020.05.033.

67. H. Wang, C.-R. Chung, Z. Wang, S. Li, B.-Y. Chu, J.-T. Horng, J.-J. Lu, and T.-Y. Lee, “A large-scale investigation and identifi-cation of methicillin-resistant Staphylococcus aureus based on peaks binning of matrix-assisted laser desorption ionization-time of flight MS spectra,” Brief. Bioinform., vol. 22, no. 3, 2021, doi: 10.1093/bib/bbaa138.

68. S. Zheng, S. J. Chung, H. C. J. Sim, et al., “Impact of formulary interventions on the minimum inhibitory concentration of methicillin-resistant Staphylococcus aureus to mupirocin, chlorhexidine, and octenidine in a Singapore tertiary institution,” Eur. J. Clin. Microbiol. Infect. Dis., vol. 39, pp. 2397–2403, 2020, doi: 10.1007/s10096-020-03814-6.

69. B. Onowska, J. Sawiński, K. Garbacz, et al., “N-(2-Arylmethylthio-4-chloro-5-methylbenzenesulfonyl)amide derivatives as potential antimicrobial agents—Synthesis and biological studies,” Int. J. Mol. Sci., vol. 21, no. 1, 2020, doi: 10.3390/ijms21010161.

70. H. Chen, Y. Yin, X. Li, S. Li, H. Gao, X. Wang, Y. Zhang, Y. Liu, and H. Wang, “Whole-genome analysis of livestock-associated methicillin-resistant Staphylococcus aureus sequence type 398 strains isolated from patients with bacteremia in China,” J. Infect. Dis., vol. 221, no. Suppl. 2, pp. S220–S228, 2020, doi: 10.1093/infdis/jiz575.

71. Y. D. Bakthavatchalam, A. Shankar, R. Muniyasamy, J. V. Peter, M. Zervos, H. T. Dwarakanathan, K. Gunasekaran, R. Iyadurai, and B. Veeraraghavan, “Levonadifloxacin, a recently approved benzoquinolizine fluoroquinolone, exhibits potent in vitro ac-tivity against contemporary Staphylococcus aureus isolates and Bengal Bay clone isolates collected from a large Indian tertiary care hospital,” J. Antimicrob. Chemother., vol. 75, no. 8, pp. 2156–2159, 2020, doi: 10.1093/jac/dkaa142.

72. P. Awolade, N. Cele, E. O. Ebenezer, et al., “Synthesis of 1H-1,2,3-Triazole-linked quinoline isatin molecular hybrids as an-ti-breast cancer and anti-methicillin-resistant Staphylococcus aureus (MRSA) agents,” Anti-Cancer Agents Med. Chem., vol. 20, no. 10, pp. 1228-1239, 2020, doi: 10.2174/1871520620666200929153138.

73. L. A. Kelley, S. Mezulis, C. M. Yates, M. N. Wass, and M. J. Sternberg, “The Phyre2 web portal for protein modelling, prediction and analysis,” Nat. Protoc., vol. 10, no. 6, pp. 845–858, 2015, doi: 10.1038/nprot.2015.053.

74. E. Lorentzen, B. Siebers, R. Hensel, and E. Pohl, “Mechanism of the Schiff base forming fructose-1,6-bisphosphate aldolase: Structural analysis of reaction intermediates,” Biochemistry, vol. 44, pp. 4222–4229, 2005, doi: 10.1021/bi050157n.

75. S. Zgiby, A. R. Plater, M. A. Bates, G. J. Thomson, and A. Berry, “A functional role for a flexible loop containing Glu182 in the class II fructose-1,6-bisphosphate aldolase from Escherichia coli,” J. Mol. Biol., vol. 315, no. 2, pp. 131–140, 2002, doi: 10.1006/jmbi.2001.5237.

76. A. Galkin, L. Kulakova, E. Melamud, L. Li, C. Wu, P. Mariano, D. Dunaway-Mariano, T. E. Nash, and O. Herzberg, “Charac-terization, kinetics, and crystal structures of fructose-1,6-bisphosphate aldolase from the human parasite, Giardia lamblia,” J. Biol. Chem., vol. 282, pp. 4859–4867, 2007, doi: 10.1074/jbc.M609121200.

77. S. Y. Gerdes, M. D. Scholle, J. W. Campbell, G. Balazsi, E. Ravasz, M. D. Daugherty, et al., “Experimental determination and system level analysis of essential genes in Escherichia coli MG1655,” J. Bacteriol., vol. 185, pp. 5673–5684, 2003, doi: 10.1128/JB.185.19.5673-5684.2003.

78. E. O. Davis, M. C. Jones-Mortimer, and P. J. Henderson, “Location of a structural gene for xyloseH+ symport at 91 min on the linkage map of Escherichia coli K12,” J. Biol. Chem., vol. 259, pp. 1520–1525, 1984, doi: 10.1016/S0021-9258(18)43454-1.

79. I. Rosenkrands, R. A. Slayden, J. Crawford, C. Aagaard, C. E. 3rd Barry, and P. H. Andersen, “Hypoxic response of Mycobacte-rium tuberculosis studied by metabolic labeling and proteome analysis of cellular and extracellular proteins,” J. Bacteriol., vol. 184, pp. 3485–3491, 2002, doi: 10.1128/JB.184.12.3485-3491.2002.

80. K. Huynh and C. L. Partch, “Analysis of protein stability and ligand interactions by thermal shift assay,” Curr. Protoc. Protein Sci., vol. 79, pp. 28.9.1–28.9.14, 2015, doi: 10.1002/0471140864.ps2809s79.

81. G. C. Capodagli, S. A. Lee, K. J. Boehm, K. M. Brady, and S. D. Pegan, “Structural and functional characterization of methicil-lin-resistant Staphylococcus aureus's class IIb fructose 1,6-bisphosphate aldolase,” Biochemistry, vol. 53, no. 48, pp. 7604–7614, Dec. 2014, doi: 10.1021/bi501141t.

82. M. Shehadul Islam, A. Aryasomayajula, and P. R. Selvaganapathy, “A review on macroscale and microscale cell lysis methods,” Micromachines, vol. 8, no. 3, p. 83, 2017, doi: 10.3390/mi8030083.

83. K. Gangele and K. M. Poluri, “Imidazole derivatives differentially destabilize the low pH conformation of lysozyme through weak electrostatic interactions,” RSC Adv., vol. 10, p. 1039, 2016, doi: 10.1039/C6RA23031H.

84. M. Tataruch, et al., “Catalytic stability of S-1-(4-hydroxyphenyl)-ethanol dehydrogenase from Aromatoleum aromaticum,” Int. J. Mol. Sci., vol. 25, no. 13, 2024, doi: 10.3390/ijms25137385.

85. Q. Zhang, et al., “Interaction mechanism and compatibility studies of silk protein peptide (SPP) with the common surfactants SDS and DTAB,” Spectrochim. Acta A Mol. Biomol. Spectrosc., vol. 322, p. 124833, 2024, doi: 10.1016/j.saa.2024.124833.

86. B. Van den Wouwer, et al., “The effect of ultrasound on the extraction and foaming properties of proteins from potato trim-mings,” Food Chem., vol. 455, p. 139877, 2024, doi: 10.1016/j.foodchem.2024.139877.

87. N. Nawaz, et al., “Lysozyme and its application as antibacterial agent in food industry,” Molecules, vol. 27, no. 19, 2022, doi: 10.3390/molecules27196305.

88. A. Flourieusse, et al., “Formation of intracellular vesicles within the Gram (+) Lactococcus lactis induced by the overexpression of Caveolin-1beta,” Microb. Cell Fact., vol. 21, p. 239, 2022, doi: 10.1186/s12934-022-01944-9.

89. G. Salvi, P. De Los Rios, and M. Vendruscolo, “Effective interactions between chaotropic agents and proteins,” Proteins, vol. 61, no. 3, pp. 492–499, Nov. 2005, doi: 10.1002/prot.20626.

90. G. C. Capodagli, W. G. Sedhom, M. Jackson, K. A. Ahrendt, and S. D. Pegan, “A noncompetitive inhibitor for Mycobacterium tuberculosis's class IIa fructose-1,6-bisphosphate aldolase,” Biochemistry, vol. 53, no. 1, pp. 202–213, Jan. 2014, doi: 10.1021/bi401022b.

91. A. Waterhouse, M. Bertoni, S. Bienert, G. Tauriello, R. Gumienny, T. Schwede, “SWISS-MODEL: homology modelling of pro-tein structures and complexes,” Nucleic Acids Res., vol. 46, no. W1, pp. W296–W303, 2018, doi: 10.1093/nar/gky427.

92. K. Palanisamy, M. Prakash, and V. Rajapandian, “Combined DFT and MD simulation studies of protein stability on imidazo-lium–water (ImH+Wn) clusters with aromatic amino acids,” New J. Chem., vol. 44, pp. 17912–17923, 2020, doi: 10.1039/D0NJ03085F.

93. M. de la Paz Santangelo, et al., “Glycolytic and non-glycolytic functions of Mycobacterium tuberculosis fructose-1,6-bisphosphate aldolase, an essential enzyme produced by replicating and non-replicating bacilli,” J. Biol. Chem., vol. 286, pp. 40219–40231, 2011, doi: 10.1074/jbc.M111.259440.

94. A. Waterhouse, M. Bertoni, S. Bienert, G. Tauriello, R. Gumienny, T. Schwede, “SWISS-MODEL: homology modelling of pro-tein structures and complexes,” Nucleic Acids Res., vol. 46, no. W1, pp. W296–W303, 2018, doi: 10.1093/nar/gky427.

95. J. Schulze Wischeler, A. Innocenti, D. Vullo, A. Agrawal, S. M. Cohen, A. Heine, C. T. Supuran, and G. Klebe, “Bidentate zinc chelators for alpha-carbonic anhydrases that produce a trigonal bipyramidal coordination geometry,” ChemMedChem, vol. 5, no. 9, pp. 1609–1615, Sep. 2010, doi: 10.1002/cmdc.201000200.

96. P. J. Mahanta and K. Lhouvum, “Expression and biochemical characterization of the putative insulinase enzyme PF11_0189 found in the Plasmodium falciparum genome,” Protein Expr. Purif., vol. 222, p. 106539, 2024, doi: 10.1016/j.pep.2024.106539.

97. S. Gu, et al., “Expression and functional analysis of the metallothionein and metal-responsive transcription factor 1 in Phasco-losoma esculenta under Zn stress,” Int. J. Mol. Sci., vol. 25, no. 13, 2024, doi: 10.3390/ijms25137368.

98. K. Varnagy, et al., “Complex formation and hydrolytic processes of protected peptides containing the -SXH- motif in the presence of nickel (II) ion,” Chembiochem, vol. 25, no. 20, e202400475, 2024, doi: 10.1002/cbic.202400475.

99. D. A. Gonzalez, et al., “Preparation and characterization of Zn (II)-stabilized Abeta (42) oligomers,” ACS Chem. Neurosci., vol. 15, no. 14, pp. 2586–2599, 2024, doi: 10.1021/acschemneuro.4c00084.

100. A. Scozzafava and C. T. Supuran, “Hydroxyurea is a carbonic anhydrase inhibitor,” Bioorg. Med. Chem., vol. 11, no. 10, pp. 2241–2246, 2003, doi: 10.1016/S0968-0896(03)00112-3.

101. M. Glavare, M. Löfgren, and M. L. Schult, “Between unemployment and employment: experience of unemployed long-term pain sufferers,” Work, vol. 43, no. 4, pp. 475–485, 2012, doi: 10.3233/WOR-2012-1394.

102. Y. Y. Chou, R. Vafabakhsh, S. Doğanay, Q. Gao, T. Ha, and P. Palese, “One influenza virus particle packages eight unique viral RNAs as shown by FISH analysis,” Proc. Natl. Acad. Sci. U.S.A., vol. 109, no. 23, pp. 9101–9106, Jun. 2012, doi: 10.1073/pnas.1206069109.

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10 May 2025

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Z. Liu , Tran., “Computational and Experimental Drug Discovery Targeting the Glycolytic Pathway in Methicillin-Resistant Staphylococcus Aureus”, J. Med. Life Sci., vol. 1, no. 3, pp. 14–45, May 2025, doi: 10.71222/s0kt8x87.