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Klebsiella pneumoniae Infection in Alveolar Type II Epithelial Cells; Antibiotic-Vitamin Combination Therapeutic Effect

Year 2023, Volume: 33 Issue: 5, 503 - 508, 25.10.2023
https://doi.org/10.54005/geneltip.1292360

Abstract

Aim: In this study, it was aimed to establish an infection model with Klebsiella pneumoniae on A549 Lung cancer cell line and to evaluate the effect of additional vitamins on the antibacterial effect of ampicillin sulbactam in the treatment. Cell culture and pathology results were determined in parallel with microbial analysis.
Methods: Minimal inhibitory concentration (MIC), fractional inhibitory concentration (FIC), biofilm optical density of ampicillin sulbactam, vitamins E, K1 and P on Klebicella pneumoniae ATCC 700603 strain were determined. Cytotoxic activity on A549 cancer cell line in parallel with microbial analysis and pathology results were determined.
Results: Ampicillin Sulbactam MIC dose range used in the treatment of Klebsiella pneumoniae infection is 16 mg/L. Looking at the FIC dose ranges, Vitamin K1+Ampicillin sulbactam, Vitamin P+Ampicillin sulbactam 2.5mg/ml+0.5µg/ml, Vitamin E+Ampicillin sulbactam 5mg/ml+0.5µg/ml, K1+P+E+Ampicillin sulbactam 2,5mg/ml+2.5mg/ml+5mg/ml+0.5µg/ml it was determined that it was. It was determined that it has a synergistic effect in combination with vitamins K1 and P antibiotics. In addition, in the presence of biofilm below 570 nm, the OD values of K1, P, E and K1+P+E+ antibiotic combinations were found to be 1.006, 0.969, 1.096 and 1.015, respectively. As a result of cell culture studies and evaluation of pathology results, it was determined that increasing the dose of Ampicillin sulbactam to 8 µg/ml increased the antibacterial effect and the vitamin combination was more effective.
Conclusions: Antibiotic and vitamin combination was found to be more effective in Klebsiella pneumoniae infection in our study. This situation contributes to the search for alternative antimicrobials.

References

  • Ding L, Yang Z, Lu J, Ma L, Liu Y, Wu X, et al. Characterization of phenotypic and genotypic traits of Klebsiella pneumoniae from lung cancer patients with respiratory infection. Infect Drug Resist 2020; 237-245.
  • Wyres KL, Lam MM, Holt KE. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol 2020;18(6): 344-359.
  • Wang G, Zhao G, Chao X, Xie L, Wang H. The characteristic of virulence, biofilm, and antibiotic resistance of Klebsiella pneumoniae. Int J Environ Res Public Health 2020; 17 (17): 6278.
  • Padmini N, Ajilda AAK, Sivakumar N, Selvakumar G. Extended spectrum β‐lactamase producing Escherichia coli and Klebsiella pneumoniae: critical tools for antibiotic resistance pattern. J Basic Microbiol 2017; 57(6): 460-470.
  • Navon-Venezia S, Kondratyeva K, Carattoli A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev 2017;41:252-275.
  • Vardakas KZ, Tansarli GS, Rafailidis PI, Falagas ME. Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis. J Antimicrob Chemother 2012;67:2793-2803.
  • Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin Infect Dis 2011;53:60-67.
  • Loh AH, Cohen AH. Drug-induced kidney disease-pathology and current concepts. Ann Acad Med Singapore 38(3): 240-250.
  • Poirel L, Nordmann P. Lack of polymyxin resistance among carbapenemase-producing Enterobacteriaceae in a university hospital in China. Infect Dis (London, England) 2017; 49(7): 556-557.
  • Zhang HM, Wakisaka N, Maeda O, Yamamoto T. Vitamin C inhibits the growth of a bacterial risk factor for gastric carcinoma: Helicobacter pylori. Cancer: Interdisciplinary International Journal of the American Cancer Society 1997; 80(10): 1897-1903.
  • Al-Salih DAAK, Aziz FM, Mshimesh BAR, Jehad MT. Antibacterial effects of vitamin E: In vitro study. J Biotechnol Res Cent 2013; 7(2): 17-23.
  • Bidossi A, Bortolin M, Toscano M, De Vecchi E, Romanò CL, Mattina R, Drago L. In vitro comparison between α-tocopheryl acetate and α-tocopheryl phosphate against bacteria responsible of prosthetic and joint infections. PLoS One 2017;12(7):e0182323.
  • Antal AS, Dombrowski Y, Koglin S, Ruzicka T, Schauber J. Impact of vitamin D3 on cutaneous immunity and antimicrobial peptide expression. Dermatoendocrinology 2011; 3(1): 18-22.
  • Zhao Y, Zhang W, Jia Q, Feng Z, Guo J, Han X, Liu WJ. High dose vitamin E attenuates diabetic nephropathy via alleviation of autophagic stress. Front Physiol 2019; 9:1939.
  • Andrade JC, Braga MFBM, Guedes GMM, Tintino SR, Freitas MA, Quintans Jr LJ, Coutinho HD. Menadione (vitamin K) enhances the antibiotic activity of drugs by cell membrane permeabilization mechanism. Saudi J Biol Sci 2017;24:59-64.
  • Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. European Journal of Emergency Medicine 2005;12(2):78-85.
  • Shahzad S, Ashraf MA, Sajid M, Shahzad A, Rafique A, Mahmood MS. Evaluation of synergistic antimicrobial effect of vitamins (A, B1, B2, B6, B12, C, D, E and K) with antibiotics against resistant bacterial strains. Journal of global antimicrobial resistance 2018;13:231-236.
  • Çelebi Ö, Çelebi D, Taghizadehghalehjoughi A, Başer S, Güler MC, Yıldırım S. The Antibacterial Effect of Boron Compounds and Evaluation of The Effects on Biofilm Formation in The Infection Model of Klebsiella pneumoniae on The Hepg2 Cell Line. J.Contemp. Med. 2023;13(1): 12-18.
  • Çelebi Ö, Çelebi D, Taghizadehghalehjoughi A, Başer S, Güler MC, Yıldırım S. Evaluation of The Effect of The Combination of Boron Compounds on Chronic Liver Disease. J.Contemp. Med.2023; 13(2): 163-169.
  • Celebi D, Taghizadehghalehjoughi A, Baser S, Genc S, Yilmaz A, Yeni, Y. Effects of boric acid and potassium metaborate on cytokine levels and redox stress parameters in a wound model infected with methicillin‑resistant Staphylococcus aureus. Mol. Med. Rep. 2022; 26(3): 1-11.
  • Celebi D, Celebi O, Baser S, Taghizadehghalehjoughi A.Evaluation of antimicrobial and antibiofilm efficacy of bee venom and exosome against Escherichia coli K99 strain. Kafkas Univ Vet Fak Derg. 2023; 29 (3): 239-246.
  • Ribeiro SM, Cardoso MH, Candido EDS, Franco OL. Understanding, preventing and eradicating Klebsiella pneumoniae biofilms. Future Microbiol 2016;11(4), 527-538.
  • Pandit S, Ravikumar V, Abdel-Haleem AM, Derouiche A, Mokkapati VRSS, Sihlbom C, Mijakovic I. Low concentrations of vitamin C reduce the synthesis of extracellular polymers and destabilize bacterial biofilms. Front Microbiol. 2017;8:2599.
  • Naguib MM, Valvano M A. Vitamin E increases antimicrobial sensitivity by inhibiting bacterial lipocalin antibiotic binding. Msphere 2018; 3(6): e00564-18.
  • Hartzen SH, Frimodt-Møller N, Frølund Thomsen V. The antibacterial activity of a siderophore.1. In vitro activity of deferoxamine alone and in combination with ascorbic acid on Staphylococcus aureus. APMIS. 1989;97(5):419-424.

Alveolar Tip II Epitel Hücrelerinde Klebsiella pneumoniae Enfeksiyonu; Antibiyotik-Vitamin Kombinasyonunun Terapötik Etkisi

Year 2023, Volume: 33 Issue: 5, 503 - 508, 25.10.2023
https://doi.org/10.54005/geneltip.1292360

Abstract

Amaç: Bu çalışmada A549 Akciğer kanseri hücre hattı üzerinde Klebsiella pneumoniae ile enfeksiyon modeli oluşturup tedavide ampisilin sülbaktam antibakteriyel etkisine ek vitaminlerin etkisini değerlendirmesi amaçlandı. Mikrobiyal analiz ile paralel olarak hücre kültürü ve patoloji sonuçları belirlendi.
Yöntemler: Klebisella pneumoniae ATCC 700603 suşu üzerinde ampisilin sülbaktam, E, K1 ve P vitamininin minimal inhibitör konsantrasyonu (MİK), franksiyonel inhibitör konsantrasyonu (FİK), etkinlik gösterdiği biyofilm optik dansitesi belirlendi.Mikrobiyal analiz ile paralel olarak A549 kanser hücre hattı üzerinde sitotoksik aktivitesi ve patoloji sonuçları belirlendi.
Bulgular: Klebsiella pneumoniae enfeksiyonunun tedavisinde kullanılan Ampisilin Sulbaktam MİK doz aralığı 16 mg/L'dir. FİK doz aralıklarına bakıldığında Vitamin K1+Ampisilin sülbaktam, Vitamin P+Ampisilin sülbaktam 2.5mg/ml+0.5µg/ml, Vitamin E+Ampisilin sülbaktam 5mg/ml+0,5µg/ml, K1+P+E+Ampisilin sülbaktam 2,5mg/ml+2,5mg/ml+5mg/ml+0,5µg/ml olduğu belirlendi. Vitamin K1 ve P antibiyotik ile kombinasyon halinde sinerjistik etki gösterdiği belirlendi. Ayrıca 570 nm altında biyofilm varlığında K1,P,E ve K1+P+E+ antibiyotik kombinasyonlarının OD değerleri sırasıyla 1.006, 0.969, 1.096 ve 1.015 olarak bulundu. Hücre kültürü çalışmaları ve patoloji sonuçlarının değerlendirilmesi sonucunda Ampisilin sülbaktam dozunun 8 µg/ml'ye çıkarılması antibakteriyel etkiyi arttırdığı ve vitamin kombinasyonun daha etkili olduğu belirlendi.
Sonuç: Çalışmamızda oluşturulan Klebsiella pneumoniae enfeksiyonunda antibiyotik ve vitamin kombinasyonun daha etkili olduğu bulundu. Bu durum alternatif antimikrobiyal arayışlarına katkı sağlamaktadır.

References

  • Ding L, Yang Z, Lu J, Ma L, Liu Y, Wu X, et al. Characterization of phenotypic and genotypic traits of Klebsiella pneumoniae from lung cancer patients with respiratory infection. Infect Drug Resist 2020; 237-245.
  • Wyres KL, Lam MM, Holt KE. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol 2020;18(6): 344-359.
  • Wang G, Zhao G, Chao X, Xie L, Wang H. The characteristic of virulence, biofilm, and antibiotic resistance of Klebsiella pneumoniae. Int J Environ Res Public Health 2020; 17 (17): 6278.
  • Padmini N, Ajilda AAK, Sivakumar N, Selvakumar G. Extended spectrum β‐lactamase producing Escherichia coli and Klebsiella pneumoniae: critical tools for antibiotic resistance pattern. J Basic Microbiol 2017; 57(6): 460-470.
  • Navon-Venezia S, Kondratyeva K, Carattoli A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev 2017;41:252-275.
  • Vardakas KZ, Tansarli GS, Rafailidis PI, Falagas ME. Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis. J Antimicrob Chemother 2012;67:2793-2803.
  • Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin Infect Dis 2011;53:60-67.
  • Loh AH, Cohen AH. Drug-induced kidney disease-pathology and current concepts. Ann Acad Med Singapore 38(3): 240-250.
  • Poirel L, Nordmann P. Lack of polymyxin resistance among carbapenemase-producing Enterobacteriaceae in a university hospital in China. Infect Dis (London, England) 2017; 49(7): 556-557.
  • Zhang HM, Wakisaka N, Maeda O, Yamamoto T. Vitamin C inhibits the growth of a bacterial risk factor for gastric carcinoma: Helicobacter pylori. Cancer: Interdisciplinary International Journal of the American Cancer Society 1997; 80(10): 1897-1903.
  • Al-Salih DAAK, Aziz FM, Mshimesh BAR, Jehad MT. Antibacterial effects of vitamin E: In vitro study. J Biotechnol Res Cent 2013; 7(2): 17-23.
  • Bidossi A, Bortolin M, Toscano M, De Vecchi E, Romanò CL, Mattina R, Drago L. In vitro comparison between α-tocopheryl acetate and α-tocopheryl phosphate against bacteria responsible of prosthetic and joint infections. PLoS One 2017;12(7):e0182323.
  • Antal AS, Dombrowski Y, Koglin S, Ruzicka T, Schauber J. Impact of vitamin D3 on cutaneous immunity and antimicrobial peptide expression. Dermatoendocrinology 2011; 3(1): 18-22.
  • Zhao Y, Zhang W, Jia Q, Feng Z, Guo J, Han X, Liu WJ. High dose vitamin E attenuates diabetic nephropathy via alleviation of autophagic stress. Front Physiol 2019; 9:1939.
  • Andrade JC, Braga MFBM, Guedes GMM, Tintino SR, Freitas MA, Quintans Jr LJ, Coutinho HD. Menadione (vitamin K) enhances the antibiotic activity of drugs by cell membrane permeabilization mechanism. Saudi J Biol Sci 2017;24:59-64.
  • Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. European Journal of Emergency Medicine 2005;12(2):78-85.
  • Shahzad S, Ashraf MA, Sajid M, Shahzad A, Rafique A, Mahmood MS. Evaluation of synergistic antimicrobial effect of vitamins (A, B1, B2, B6, B12, C, D, E and K) with antibiotics against resistant bacterial strains. Journal of global antimicrobial resistance 2018;13:231-236.
  • Çelebi Ö, Çelebi D, Taghizadehghalehjoughi A, Başer S, Güler MC, Yıldırım S. The Antibacterial Effect of Boron Compounds and Evaluation of The Effects on Biofilm Formation in The Infection Model of Klebsiella pneumoniae on The Hepg2 Cell Line. J.Contemp. Med. 2023;13(1): 12-18.
  • Çelebi Ö, Çelebi D, Taghizadehghalehjoughi A, Başer S, Güler MC, Yıldırım S. Evaluation of The Effect of The Combination of Boron Compounds on Chronic Liver Disease. J.Contemp. Med.2023; 13(2): 163-169.
  • Celebi D, Taghizadehghalehjoughi A, Baser S, Genc S, Yilmaz A, Yeni, Y. Effects of boric acid and potassium metaborate on cytokine levels and redox stress parameters in a wound model infected with methicillin‑resistant Staphylococcus aureus. Mol. Med. Rep. 2022; 26(3): 1-11.
  • Celebi D, Celebi O, Baser S, Taghizadehghalehjoughi A.Evaluation of antimicrobial and antibiofilm efficacy of bee venom and exosome against Escherichia coli K99 strain. Kafkas Univ Vet Fak Derg. 2023; 29 (3): 239-246.
  • Ribeiro SM, Cardoso MH, Candido EDS, Franco OL. Understanding, preventing and eradicating Klebsiella pneumoniae biofilms. Future Microbiol 2016;11(4), 527-538.
  • Pandit S, Ravikumar V, Abdel-Haleem AM, Derouiche A, Mokkapati VRSS, Sihlbom C, Mijakovic I. Low concentrations of vitamin C reduce the synthesis of extracellular polymers and destabilize bacterial biofilms. Front Microbiol. 2017;8:2599.
  • Naguib MM, Valvano M A. Vitamin E increases antimicrobial sensitivity by inhibiting bacterial lipocalin antibiotic binding. Msphere 2018; 3(6): e00564-18.
  • Hartzen SH, Frimodt-Møller N, Frølund Thomsen V. The antibacterial activity of a siderophore.1. In vitro activity of deferoxamine alone and in combination with ascorbic acid on Staphylococcus aureus. APMIS. 1989;97(5):419-424.
There are 25 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Original Article
Authors

Özgür Çelebi 0000-0003-4578-9474

Demet Çelebi 0000-0002-2355-0561

Sümeyye Başer 0000-0003-2391-8191

Serkan Yıldırım 0000-0003-2457-3367

Mustafa Can Güler 0000-0001-8588-1035

Ali Taghizadehghalehjoughi 0000-0002-3506-0324

Early Pub Date October 23, 2023
Publication Date October 25, 2023
Submission Date May 4, 2023
Published in Issue Year 2023 Volume: 33 Issue: 5

Cite

Vancouver Çelebi Ö, Çelebi D, Başer S, Yıldırım S, Güler MC, Taghizadehghalehjoughi A. Klebsiella pneumoniae Infection in Alveolar Type II Epithelial Cells; Antibiotic-Vitamin Combination Therapeutic Effect. Genel Tıp Derg. 2023;33(5):503-8.

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