{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:58:14Z","timestamp":1788325094842,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fonds de recherche du Qu\u00e9bec\u2014Nature et technologies (FRQNT) strategic cluster","award":["RS-170946"],"award-info":[{"award-number":["RS-170946"]}]},{"name":"Swine and Poultry Infectious Diseases Research Center (CRIPA)","award":["RS-170946"],"award-info":[{"award-number":["RS-170946"]}]},{"name":"Canada Research Chair","award":["RS-170946"],"award-info":[{"award-number":["RS-170946"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>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 \u00b1 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.<\/jats:p>","DOI":"10.3390\/nano12132179","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T21:01:41Z","timestamp":1656277301000},"page":"2179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Nanoparticle-Enabled Combination Therapy Showed Superior Activity against Multi-Drug Resistant Bacterial Pathogens in Comparison to Free Drugs"],"prefix":"10.3390","volume":"12","author":[{"given":"Amarpreet","family":"Brar","sequence":"first","affiliation":[{"name":"Department of Food Science and Agricultural Chemistry, Macdonald Campus, McGill University, 21111 Lakeshore, Ste Anne de Bellevue, QC H9X 3V9, Canada"},{"name":"Swine and Poultry Infectious Diseases Research Center (CRIPA), Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, 3200 Sicotte, Saint-Hyacinthe, QC J2S 2M2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-4536","authenticated-orcid":false,"given":"Satwik","family":"Majumder","sequence":"additional","affiliation":[{"name":"Department of Food Science and Agricultural Chemistry, Macdonald Campus, McGill University, 21111 Lakeshore, Ste Anne de Bellevue, QC H9X 3V9, Canada"},{"name":"Swine and Poultry Infectious Diseases Research Center (CRIPA), Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, 3200 Sicotte, Saint-Hyacinthe, QC J2S 2M2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Zardon","family":"Navarro","sequence":"additional","affiliation":[{"name":"Swine and Poultry Infectious Diseases Research Center (CRIPA), Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, 3200 Sicotte, Saint-Hyacinthe, QC J2S 2M2, Canada"},{"name":"Research Group on Infectious Diseases in Production Animals (GREMIP), Department of Pathology and Microbiology, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, 3200 Sicotte, Saint-Hyacinthe, QC J2S 2M2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Odile","family":"Benoit-Biancamano","sequence":"additional","affiliation":[{"name":"Swine and Poultry Infectious Diseases Research Center (CRIPA), Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, 3200 Sicotte, Saint-Hyacinthe, QC J2S 2M2, Canada"},{"name":"Research Group on Infectious Diseases in Production Animals (GREMIP), Department of Pathology and Microbiology, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, 3200 Sicotte, Saint-Hyacinthe, QC J2S 2M2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Ronholm","sequence":"additional","affiliation":[{"name":"Department of Food Science and Agricultural Chemistry, Macdonald Campus, McGill University, 21111 Lakeshore, Ste Anne de Bellevue, QC H9X 3V9, Canada"},{"name":"Department of Animal Science, Macdonald Campus, McGill University, 2111 Lakeshore, Ste Anne de Bellevue, QC H9X 3V9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8807-0737","authenticated-orcid":false,"given":"Saji","family":"George","sequence":"additional","affiliation":[{"name":"Department of Food Science and Agricultural Chemistry, Macdonald Campus, McGill University, 21111 Lakeshore, Ste Anne de Bellevue, QC H9X 3V9, Canada"},{"name":"Swine and Poultry Infectious Diseases Research Center (CRIPA), Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, 3200 Sicotte, Saint-Hyacinthe, QC J2S 2M2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.2105\/AJPH.2015.302870","article-title":"Antibiotics Overuse in Animal Agriculture: A Call to Action for Health Care Providers","volume":"105","author":"Martin","year":"2015","journal-title":"Am. 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