Data_Sheet_1_Characterization of extended-spectrum cephalosporins and fluoroquinolone resistance of a Salmonella enterica serovar Thompson isolate from ready-to-eat pork product in China.docx

Salmonella is a leading cause of foodborne illness worldwide and is a common concern in food safety. Salmonella enterica displaying resistance to extended-spectrum cephalosporins (ESCs) and fluoroquinolone (FQs) has been deemed a high-priority pathogen by the World Health Organization. Co-resistance to ESCs and FQs has been reported in S. enterica serovar Thompson (S. Thompson). However, the genetic context of ESCs and FQs resistance genes in S. Thompson lacks sufficient characterization. In this study, we characterized a multi-drug resistant (MDR) S. Thompson isolate recovered from a retail ready-to-eat (RTE) pork product in China. Short- and long-read sequencing (HiSeq and MinION) of the genome identified the presence of blaCMY−2, qnrS1, and qepA8, along with 11 additional acquired antimicrobial resistance genes, residing on a 152,940 bp IncA/C plasmid. Specifically, the blaCMY−2, qnrS1, and qepA8 genes were located in insertion sequences (ISs) and integron mediated mobile genetic structure, sugE-blc-blaCMY−2-ISEc9, IS26-orf6-qnrS1-orf5-ISKpn19, and intl1-qepA8-orf10-IS91-orf1-dfrA12-orf11-aadA2-qacEΔ1-sul1, respectively. Each gene was identified in various bacteria species, indicating their high transfer ability. The plasmid was found to be transferable to Escherichia coli J53 by conjugation and resulted in the acquiring of multiple resistances in the transconjugants. The plasmid is closely related to plasmids from two human S. Thompson strains isolated in different regions and years in China. Moreover, core-genome Multi Locus Sequence Typing (cgMLST) and phylogenetic analysis based on global 1,868 S. Saintpaul isolates showed that the S. Thompson isolate was highly epidemiologically linked to a human isolate in China. Our findings suggest that Chinese RTE pork products are a possible source of human pathogenic ESCs and FQs co-resistant S. Thompson. Furthermore, the results underline the important role of conjugative plasmids in acquiring and transmission of ESCs and FQs resistance in S. Thompson isolates, which need continuous investigation.</p

Table_1_Characterization of extended-spectrum cephalosporins and fluoroquinolone resistance of a Salmonella enterica serovar Thompson isolate from ready-to-eat pork product in China.xlsx

Salmonella is a leading cause of foodborne illness worldwide and is a common concern in food safety. Salmonella enterica displaying resistance to extended-spectrum cephalosporins (ESCs) and fluoroquinolone (FQs) has been deemed a high-priority pathogen by the World Health Organization. Co-resistance to ESCs and FQs has been reported in S. enterica serovar Thompson (S. Thompson). However, the genetic context of ESCs and FQs resistance genes in S. Thompson lacks sufficient characterization. In this study, we characterized a multi-drug resistant (MDR) S. Thompson isolate recovered from a retail ready-to-eat (RTE) pork product in China. Short- and long-read sequencing (HiSeq and MinION) of the genome identified the presence of blaCMY−2, qnrS1, and qepA8, along with 11 additional acquired antimicrobial resistance genes, residing on a 152,940 bp IncA/C plasmid. Specifically, the blaCMY−2, qnrS1, and qepA8 genes were located in insertion sequences (ISs) and integron mediated mobile genetic structure, sugE-blc-blaCMY−2-ISEc9, IS26-orf6-qnrS1-orf5-ISKpn19, and intl1-qepA8-orf10-IS91-orf1-dfrA12-orf11-aadA2-qacEΔ1-sul1, respectively. Each gene was identified in various bacteria species, indicating their high transfer ability. The plasmid was found to be transferable to Escherichia coli J53 by conjugation and resulted in the acquiring of multiple resistances in the transconjugants. The plasmid is closely related to plasmids from two human S. Thompson strains isolated in different regions and years in China. Moreover, core-genome Multi Locus Sequence Typing (cgMLST) and phylogenetic analysis based on global 1,868 S. Saintpaul isolates showed that the S. Thompson isolate was highly epidemiologically linked to a human isolate in China. Our findings suggest that Chinese RTE pork products are a possible source of human pathogenic ESCs and FQs co-resistant S. Thompson. Furthermore, the results underline the important role of conjugative plasmids in acquiring and transmission of ESCs and FQs resistance in S. Thompson isolates, which need continuous investigation.</p

Treatment with high-dose antidepressants severely exacerbates the pathological outcome of experimental <i>Escherichia coli</i> infections in poultry

<div><p>There is an urgent need for novel antibiotics as the current antibiotics are losing their value due to increased resistance among clinically important bacteria. Sertraline, an on-marked anti-depressive drug, has been shown to modify bacterial activity <i>in vitro</i>, including increasing the susceptibility of <i>Escherichia coli</i> to antibiotics. The aim of the present study was to investigate if the antimicrobial activity of sertraline could be documented under clinical settings, hereunder if sertraline could potentiate the effect of tetracycline in treatment of an experimentally induced ascending infection in poultry. A total of 40 chickens were divided in four groups of 10 chickens each. All chickens were challenged with 4x10³ colony forming units (CFU) of a tetracycline resistant <i>E</i>. <i>coli</i> strain using a surgical infection model, and subsequently treated with either high-dose sertraline, tetracycline, a combination hereof or received no treatment. Seven days post challenge all birds were submitted to necropsy and scored pathologically for lesions. The average lesion scores were significantly higher (P<0.05) in the groups that were treated with high-dose sertraline or high-dose sertraline combined with tetracycline. In conclusion high-dose treatments (four times the maximum therapeutic dose for treating human depression) with sertraline as an adjuvant for treatment of antibiotic resistant <i>E</i>. <i>coli</i> infections exacerbate the pathological outcome of infection in chickens.</p></div

Minimal inhibitory concentration (MIC) of sertraline and tetracycline alone or combined.

<p>For each combination exposure on sertraline and tetracycline, the fractional inhibitory concentration index (FICI) is stated.</p

Overview of experimental groups.

<p>Each group consisted of 10 commercially brown layers, 45 weeks of age.</p

Colony-forming units (CFU).

<p>CFU per gram salpinx in the different treatment groups. Vertical bars indicate the standard deviation.</p

Weight changes during infection.

<p>Percent weight change seven days after infection compared to before infection per chicken in the different treatment groups.</p