Silver nanoparticles grafted onto tannic acid-modified halloysite clay eliminated multidrug-resistant Salmonella Typhimurium in a Caenorhabditis elegans model of intestinal infection

The prevalence of antimicrobial resistance (AMR) among pathogenic bacteria in livestock warrants alternate therapeutic strategies that are efficient in remediating zoonotic infections. Combination therapy with more than one antimicrobial with complementary action has shown possibilities to prevent or slow down AMR. The application of clay-based biomaterials could, however, resolve challenges of poor bioavailability, cytotoxicity, stability, release, and overdosing and play a significant role in formulating cost-effective therapeutics. In this study, a nanocomposite (GH-TA-Ag-NT) containing silver nanoparticles (Ag NPs) grafted onto tannic acid (TA)-modified halloysite nanotubes (hal NTs) was generated and compared with TA-stabilized Ag NPs (Ag-TA-NP) for physicochemical and antibacterial properties. The Transmission electron microscopy, Fourier transform infrared, Dynamic light scattering, and X-ray diffraction spectroscopies confirmed the synthesis of the nanocomposite. GH-TA-Ag-NT demonstrated enhanced stability and drug-bioavailability with a slow-release of Ag+ and TA. The nanocomposite showed superior antibacterial performance in comparison to Ag-TA-NP when tested against E. coli ATCC 25922, S. aureus ATCC 25923, and a multi-drug resistant (MDR) Salmonella enterica serovar Typhimurium (isolated from infected swine). The combinatorial effect was mediated through anti-efflux/anti-biofilm properties, oxidative stress, loss of bacterial membrane potential, and integrity. The toxicity and antibacterial efficiency of GH-TA-Ag-NT to remediate gastrointestinal infection were demonstrated in the S. Typhimurium infected Caenorhabditis elegans model. The nanocomposite was less toxic, reduced Salmonella colonization significantly within 24 h of exposure, and improved worm survivability. In summary, we demonstrated a unique and novel strategy to counter AMR bacteria by applying Nano-enabled Antibacterial Combination Therapy (NACT) with GH-TA-Ag-NT and thus propose its potential use as a therapeutic against zoonotic pathogens.