Brar Amarpreet, Majumder Satwik, Navarro Maria Zardon, Benoit-Biancamano Marie-Odile, Ronholm Jennifer, George Saji
Department of Food Science and Agricultural Chemistry, Macdonald Campus, McGill University, 21111 Lakeshore, Ste Anne de Bellevue, QC H9X 3V9, Canada.
Swine and Poultry Infectious Diseases Research Center (CRIPA), Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Sicotte, Saint-Hyacinthe, QC J2S 2M2, Canada.
Nanomaterials (Basel). 2022 Jun 24;12(13):2179. doi: 10.3390/nano12132179.
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 and take refuge inside host cells, thereby demanding intervention strategies that can eliminate intracellular MDR pathogens. In this study, seven clinical isolates of and 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 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. isolates showed complete hemolysis and strong biofilm formation, while isolates caused partial hemolysis, but showed no or weak biofilm formation. MDR isolates of M12 and 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 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 (HS) 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.
家畜中多重耐药（MDR）细菌病原体的出现及其人畜共患传播，是动物养殖业和公共卫生都关切的问题。除了抗菌药物耐药性（AMR）外，[具体菌属]和[具体菌属]的细菌病原体会在宿主细胞内隐匿，因此需要能够消除细胞内多重耐药病原体的干预策略。在本研究中，对来自养猪场的7株[具体菌属]和[具体菌属]临床分离株进行了抗生素（n = 24）耐药性、耐药机制及毒力特性的鉴定。所有分离株均对一种或多种抗生素耐药，其中鼠伤寒[具体菌属]血清型分离株对所测试的一组抗生素耐药性最高。鉴定出的主要耐药机制为外排泵和β-内酰胺酶活性。[具体菌属]分离株表现出完全溶血和强烈的生物膜形成，而[具体菌属]分离株引起部分溶血，但生物膜形成不明显或较弱。随后，使用棋盘法对M12 [具体菌属]和鼠伤寒[具体菌属]细菌的多重耐药分离株进行了抗生素与增效佐剂组合的测试，以提高抗菌效果，并计算其部分抑菌浓度指数（FICI）。对分别含有四环素（TET）和外排泵抑制剂氯丙嗪（CPZ）的壳聚糖和二氧化硅纳米颗粒组合进行了理化性质和对多重耐药鼠伤寒[具体菌属]血清型分离株有效性的鉴定。这种纳米包封药物组合通过抑制AMR机制（外排活性、β-内酰胺酶活性和硫化氢（HS）产生）提高了抗菌效果，并使细胞内病原体载量降低了83.02±14.35%。总之，本研究揭示了纳米颗粒介导的联合疗法在对抗动物养殖业中遇到的多重耐药病原体方面具有广阔的应用前景。
