Alzhraa Ali Mohamed

Turkey

Meropenem-ZnO-Nps combination against CRKP biofilms, with lower nephrotoxicity

Alzhraa Ali Mohamed1,2,*, Safaa Saed1, Sara Ramadan El-Sayed1, Mohamed Taha Yassin3, Mohamed Gad4, Eman Tartour1, Hoda A. Fathey1, Asmaa S Taha1, Asmaa H. Mohamed1, Fatimah Olyan Al-Otibi2, Mohamed Ragab Ab-delGawwad5, Mohamed M. Sayed Ahmed1, Susan Ahmed Almalki6, Mohamed Abdel?Haleem1,*

1 Microbiology and Botany Department, Faculty of Science, Zagazig University (44519), Zagazig, Egypt.
2 Graduate School of Natural and Applied Science, Ege University, Izmir, Türkiye.
3Botany and Microbiology Department, College of Science, King Saud University, (2455), Riyadh, Saudi Arabia.
4 Zoology Department, Faculty of Science, Zagazig University (44519), Zagazig, Egypt.
5 Genetics and Bioengineering Department, Faculty of Engineering and Natural Sciences, International University of Sarajevo, 71210 Sarajevo, Bosnia and Herzegovina.
6 Laboratory medicine department, Faculty of Applied Medical Sciences, Al-Baha University, 65779, Saudi Arabia.

Abstract

Background

In response to the World Health Organization’s (WHO) research agenda of antimicrobial resistance (AMR) in human health, this study appraised the antibacterial and antibiofilm synergistic activity of meropenem and ZnO-NPs combination against carbapenem-resistant Klebsiella pneumoniae (CRKP).

Methods

Microtiter dilution method was used for determination of MICs. SEM was used for evaluating the morphological changes of biofilms treated with the combination. QPCR was used for estimation of relative gene expression of biofilm genes. MTT assay was used for evaluating the cytotoxicity levels of the two agents alone and in combination.

Results

The minimum inhibitory concentration (MIC) of meropenem in combination was found to be approximately 1/12 of its MIC alone. The results of microtiter dilution assay showed that the combination was more efficient in reducing the biofilm biomass than meropenem alone or ZnO-NPs alone. The scanning-electron-microscopy (SEM) micrographs elucidated that the combination of meropenem with ZnO-NPs has significantly enhanced its competence in eradicating the preformed biofilms of CRKP strains. In addition, the relative gene expression results showed that the combination compared to the meropenem alone and ZnO-NPs alone eloquently down-regulated the expression of biofilm genes (mrkA, fimA, and ecpA). Besides, the MTT-assay demonstrated that the combination has limited cytotoxicity against Vero-cells (in vitro).

Conclusions

Overall, this study represents an efficient safe enhancement of meropenem to tackle the growing health threat of CRKP and carbapenem-resistant Enterobacterals (CRE) prevalence.