Nanoparticle-Enabled Combination Therapy Showed Superior Activity against Multi-Drug Resistant Bacterial Pathogens in Comparison to Free Drugs

The emergence of multidrug-resistant (MDR) bacterial pathogens in farm animals and their zoonotic spread is a concern to both animal agriculture and public health. Apart from antimicrobial resistance (AMR), bacterial pathogens from the genera of Salmonella and Staphylococcus take refuge inside host...

Full description

Saved in:
Bibliographic Details
Published in:Nanomaterials (Basel, Switzerland) Switzerland), 2022-06, Vol.12 (13), p.2179
Main Authors: Brar, Amarpreet, Majumder, Satwik, Navarro, Maria Zardon, Benoit-Biancamano, Marie-Odile, Ronholm, Jennifer, George, Saji
Format: Article
Language:English
Subjects:
Adjuvants
Agriculture
Animals
Antibiotics
Antimicrobial resistance
Bacteria
Biofilms
Chitosan
Chlorpromazine
Clinical isolates
combination therapy
Drug delivery systems
Drug resistance
Efflux
Enzymatic activity
Enzyme activity
Farms
Hemolysis
Hydrogen sulfide
Intracellular
multi-drug resistance
Multidrug resistance
nanoparticle
Nanoparticles
Pathogens
Physicochemical properties
Public health
Salmonella
Scanning electron microscopy
Silica
Staphylococcus
Virulence
Zoonoses
β Lactamase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The emergence of multidrug-resistant (MDR) bacterial pathogens in farm animals and their zoonotic spread is a concern to both animal agriculture and public health. Apart from antimicrobial resistance (AMR), bacterial pathogens from the genera of Salmonella and Staphylococcus take refuge inside host cells, thereby demanding intervention strategies that can eliminate intracellular MDR pathogens. In this study, seven clinical isolates of Salmonella and Staphylococcus from swine farms were characterized for antibiotic (n = 24) resistance, resistance mechanisms, and virulence characteristics. All isolates showed resistance to one or more antibiotics and S. enterica ser. Typhimurium isolate had the highest resistance to the panel of antibiotics tested. Major resistance mechanisms identified were efflux pump and beta-lactamase enzyme activities. Staphylococcus isolates showed complete hemolysis and strong biofilm formation, while Salmonella isolates caused partial hemolysis, but showed no or weak biofilm formation. MDR isolates of S. aureus M12 and S. enterica ser. Typhimurium bacteria were subsequently tested against combinations of antibiotics and potentiating adjuvants for improved antibacterial efficacy using a checkerboard assay, and their fractional inhibitory concentration index (FICI) was calculated. A combination of chitosan and silica nanoparticles containing tetracycline (TET) and efflux pump inhibitor chlorpromazine (CPZ), respectively, was characterized for physicochemical properties and effectiveness against MDR Salmonella enterica ser. Typhimurium isolate. This combination of nano-encapsulated drugs improved the antibacterial efficacy by inhibiting AMR mechanisms (efflux activity, beta-lactamase enzyme activity, and hydrogen sulfide (H2S) production) and reducing intracellular pathogen load by 83.02 ± 14.35%. In conclusion, this study sheds light on the promising applicability of nanoparticle-enabled combination therapy to combat multidrug-resistant pathogens encountered in animal agriculture.
ISSN:2079-4991
2079-4991
DOI:10.3390/nano12132179