검색옵션 상세검색
국내 의과학 학술논문 상세

Journal of Microbiology and Biotechnology. 2025 Dec; 35(0): 8508909. doi: 10.4014/jmb.2506.06023

Reviving Furosemide as a Metallo-β-Lactamase Inhibitor against MDR Acinetobacter baumannii

Hanan Al-Lawati , Fatma Al-Raisi , Mahmoud A. Elfaky , Mahmoud Saad Abdel-Halim , Hisham A. Abbas , Basem Mansour , Wael A. H. Hegazy*
Affiliations    expand

    • 원문보기

    • 조회

      상세조회 302건

  • Abstract



    Carbapenems are considered the last line of antibiotic defense against multidrug-resistant (MDR) Acinetobacter baumannii, a bacterium that can secrete carbapenemases such as metallo-β-lactamases (MBLs) to degrade carbapenems. It is thus critical to develop strategies to combat carbapenem resistance, and one of these strategies is to discover MBL inhibitors. In the current study, we evaluated the possible anti-β-lactamase of the approved safe drug furosemide. Furosemide is a loop diuretic with antihypertensive effects. A clinical MDR and carbapenem-resistant A. baumannii isolate was used. Furosemide at 1 mg/ml potentiated meropenem in the combined disk method and interfered with the hydrolytic activities of MBL. Furthermore, furosemide synergized meropenem and decreased its minimum inhibitory concentration (MIC). Furosemide could also reduce the expression of the MBL genes blaNDM and blaVIM. In silico study showed the binding ability of furosemide with the active sites of New Delhi and VIM MBL enzymes, as well as its chelating interaction with zinc ions. Furosemide is a promising MBL inhibitor that can be used in combination with meropenem to treat infections caused by MBL-producing A. baumannii.

  • Keywords

  • MeSH Term

  • References

    more references

    1. Gonzalez-Villoria AM, Valverde-Garduno V. 2016. Antibiotic-resistant Acinetobacter baumannii increasing success remains a challenge as a nosocomial pathogen. J. Pathog. 2016: 7318075.

    Article | PubMed | PMC

    2. Morris FC, Dexter C, Kostoulias X, Uddin MI, Peleg AY. 2019. The mechanisms of disease caused by Acinetobacter baumannii. Front. Microbiol. 10: 448380.

    Article | PubMed | PMC

    3. Peleg AY, Seifert H, Paterson DL. 2008. Acinetobacter baumannii: emergence of a successful pathogen. Clin. Microbiol. Rev. 21: 538-582.

    Article | PubMed | PMC

    4. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. 2014. Multistate point-prevalence survey of health care-associated infections. N. Engl. J. Med. 370: 1198-1208.

    Article | PubMed | PMC

    5. Lob SH, Hoban DJ, Sahm DF, Badal RE. 2016. Regional differences and trends in antimicrobial susceptibility of Acinetobacter baumannii. Int. J. Antimicrob. Agents 47: 317-323.

    Article | PubMed

    6. Piperaki E-T, Tzouvelekis L, Miriagou V, Daikos G. 2019. Carbapenem-resistant Acinetobacter baumannii: in pursuit of an effective treatment. Clin. Microbiol. Infect. 25: 951-957.

    Article | PubMed

    7. Ma C, McClean S. 2021. Mapping global prevalence of Acinetobacter baumannii and recent vaccine development to tackle it. Vaccines 9: 570.

    Article | PubMed | PMC

    8. Koshak AE, Okairy HM, Elfaky MA, Abdallah HM, Mohamed GA, Ibrahim SR, et al. 2024. Antimicrobial and anti-virulence activities of 4-shogaol from grains of paradise against gram-negative bacteria: integration of experimental and computational methods. J. Ethnopharmacol. 323: 117611.

    Article | PubMed

    9. Wong D, Nielsen TB, Bonomo RA, Pantapalangkoor P, Luna B, Spellberg B. 2017. Clinical and pathophysiological overview of Acinetobacter infections: a century of challenges. Clin. Microbiol. Rev. 30: 409-447.

    Article | PubMed | PMC



G
N
I
D
A
O
L