NorA is a member of the Major Facilitator Superfamily (MFS) drug efflux pumps that have been shown to mediate antibiotic resistance in Staphylococcus aureus (SA). In this study, QSAR analysis, virtual screening and molecular docking were implemented in an effort to discover novel SA NorA efflux pump inhibitors. Originally, a set of 47 structurally diverse compounds compiled from the literature was used to develop linear QSAR models and another set of 15 different compounds were chosen for extra validation. The final model which was estimated by statistical values for the full data set (n = 45, Q(2) = 0.80, RMSE = 0.20) and for the external test set (n = 15, R(2) = 0.60, |res|max = 0.75, |res|min = 0.02) was applied on the collection of 182 flavonoides and the traditional Chinese medicine (TCM) database to screen for novel NorA inhibitors. Finally, 33 lead compounds that met the Lipinski's rules of five/three and had good predicted pIC50 values from in silico screening process were employed to analyze the binding ability by docking studies on NorA homology model in place of its unavailable crystal structures at two active sites, the central channel and the Walker B.

Both disk diffusion and broth micro-dilution assays were employed to determine the level of resistance in Enterotoxigenic Escherichia coli (ETEC) isolates (n = 170) obtained from preweaning piglet colibacillosis from the two different pig production systems (commercial piggeries and small holder farmers) in Vietnam. Overall, tetracycline, streptomycin, amoxicillin, trimethoprim/sulfamethoxazole, and chloramphenicol showed markedly higher rates of resistance. Both apramycin and ceftiofur are active against all ETEC isolates. These antimicrobials could be recommended as the drugs of choice for the treatment of E. coli infections in young pigs in North Vietnam. Resistance to third-generation cephalosporin (ceftiofur, ceftazidime, and cefoxitin) was not observed in Vietnamese ETEC isolates. Multiple resistances to greater than three antimicrobials were widely distributed (approximately 79.4%).

Edema disease caused by Escherichia coli is one of the most common diseases in postweaning piglets throughout Vietnam. Verotoxigenic E. coli (VTEC) was isolated from 197 of 261 samples (75.5%). All isolates were confirmed by basic biochemical tests and carbohydrate fermentation characteristics. Of these, 70.1% of isolates are hemolytic, 45% isolates belonged to serotypes O149:K91, possessed the VT2e gene, and was the most predominant VTEC pathotype associated with edema disease in pigs. Serogroup O139 accounted for 30% of the isolates, followed by serogroup O138 and O141 (25%). In addition to VT2e gene, the ST (72.7%) and LT (52.7%) genes were also recognized. A total of 10 representative isolates were subjected to toxigenicity testing by intraperitoneal injection in mice and experimental infection in pigs. It was shown that 100% of the mice were killed 17-24 h post injection (p.i.). All pigs experimentally infected with challenge strains and developed typical symptoms of edema disease 36-72 h p.i. A multivalent killed whole-cells vaccine containing aluminum hydroxide was prepared from 5 VTEC strains. The vaccine was 100% safe when administered by the intramuscular route into the pigs. A field trial for over 100,000 pigs (21-90 days old) showed that vaccinated pigs were protected against edema disease at a level of 90% compared to 100% of pigs from unvaccinated groups.