Evaluation of bactericidal effects of silver hydrosol nanotherapeutics against Enterococcus faecium 1449 drug resistant biofilms

Alya Limayem; Mausam Mehta; Natalie Kondos; Divya Kaushal; Farhat Binte Azam; Sriram Chellappan; Nan Qin; Qingyu Zhou

doi:10.3389/fcimb.2022.1095156

Evaluation of bactericidal effects of silver hydrosol nanotherapeutics against Enterococcus faecium 1449 drug resistant biofilms

Front Cell Infect Microbiol. 2023 Jan 11:12:1095156. doi: 10.3389/fcimb.2022.1095156. eCollection 2022.

Authors

Alya Limayem^{1

2}, Mausam Mehta^{2

3}, Natalie Kondos^{2

3}, Divya Kaushal², Farhat Binte Azam⁴, Sriram Chellappan⁴, Nan Qin⁵, Qingyu Zhou²

Affiliations

¹ Department of Biology, College of Arts & Sciences, University of North Florida, Jacksonville, FL, United States.
² Department of Pharmaceutical Sciences, Graduate Program, Taneja College of Pharmacy, University of South Florida, Tampa, FL, United States.
³ Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
⁴ Department of Computer Science & Engineering, College of Engineering, University of South Florida, Tampa, FL, United States.
⁵ Department of R&D and Analytical Services, Natural Immunogenics Corporation, Sarasota, FL, United States.

Abstract

Introduction: Silver (Ag) nanoparticles (NPs) are well documented for their broad-spectrum bactericidal effects. This study aimed to test the effect of bioactive Ag-hydrosol NPs on drug-resistant E. faecium 1449 strain and explore the use of artificial intelligence (AI) for automated detection of the bacteria.

Methods: The formation of E. faecium 1449 biofilms in the absence and presence of Ag-hydrosol NPs at different concentrations ranging from 12.4 mg/L to 123 mg/L was evaluated using a 3-dimentional culture system. The biofilm reduction was evaluated using the confocal microscopy in addition to the Transmission Electronic Microscopy (TEM) visualization and spectrofluorimetric quantification using a Biotek Synergy Neo2 microplate reader. The cytotoxicity of the NPs was evaluated in human nasal epithelial cells using the MTT assay. The AI technique based on Fast Regional Convolutional Neural Network architecture was used for the automated detection of the bacteria.

Results: Treatment with Ag-hydrosol NPs at concentrations ranging from 12.4 mg/L to 123 mg/L resulted in 78.09% to 95.20% of biofilm reduction. No statistically significant difference in biofilm reduction was found among different batches of Ag-hydrosol NPs. Quantitative concentration-response relationship analysis indicated that Ag-hydrosol NPs exhibited a relative high anti-biofilm activity and low cytotoxicity with an average EC50 and TC50 values of 0.0333 and 6.55 mg/L, respectively, yielding an average therapeutic index value of 197. The AI-assisted TEM image analysis allowed automated detection of E. faecium 1449 with 97% ~ 99% accuracy.

Discussion: Conclusively, the bioactive Ag-hydrosol NP is a promising nanotherapeutic agent against drug-resistant pathogens. The AI-assisted TEM image analysis was developed with the potential to assess its treatment effect.

Keywords: multi-drug resistance; E. faecium; artificial intelligence; bactericidal treatment; bioactive silver hydrosol nanoparticles; computer vision; cytotoxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Artificial Intelligence
Biofilms
Enterococcus faecium*
Humans
Microbial Sensitivity Tests
Silver* / pharmacology

Substances

Silver
Anti-Bacterial Agents

Grants and funding

This study received funding from Natural Immunogenics Corporation and Florida High Tech Corridor (Award number 63821048 to AL and QZ). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.