|ZHANG, ZENGFENG - Shanghai Jiaotong University|
|YANG, JINGXIAN - Shanghai Jiaotong University|
|XU, XUEBIN - Shanghai Jiaotong University|
|ZHOU, XIUJUAN - Shanghai Jiaotong University|
|SHI, CHUNLEI - Shanghai Jiaotong University|
|ZHAO, XIAODONG - Shanghai Jiaotong University|
|SHI, XIANMING - Shanghai Jiaotong University|
Submitted to: Food Control
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/22/2020
Publication Date: 3/26/2020
Citation: Zhang, Z., Yang, J., Xu, X., Zhou, X., Shi, C., Zhao, X., Liu, Y., Shi, X. 2020. Co-existence of mphA, oqxAB and blaCTX-M-65 on the IncHI2 plasmid in highly drug-resistant Salmonella enterica serovar Indiana ST17 isolated from retail foods and humans in China. Food Control. doi.org/10.1016/j.foodcontrol. https://doi.org/10.1016/j.foodcont.2020.107269.
Interpretive Summary: Salmonella is a major bacterial foodborne pathogen that causes salmonellosis, and it consists of many different types referred to as serotypes. One Salmonella serotype known as Salmonella Indiana causes infection primarily through consumption of contaminated foods. Severe Salmonella infections are treated with antibiotics; however, Salmonella strains are becoming increasingly more resistant to antibiotics in China and other countries worldwide. To mitigate the development of resistance in this pathogen, it is important to understand the mechanism by which Salmonella acquires antibiotic resistance. Salmonella Indiana strains isolated from chickens, ducks, and humans were resistant to antibiotics known as azithromycin, ciprofloxacin, and ceftriaxone. The DNA sequence of a large plasmid (small circular DNA molecule that replicates independent of the bacterial chromosome) possessed by these strains was determined. The plasmid contained a large multidrug resistance region of DNA that carried 29 antibiotic resistance genes, and experiments demonstrated that resistance genes could be transferred to other bacteria. This study highlighted the emergence of S. Indiana with concurrent resistance to azithromycin, ciprofloxacin, and ceftriaxone in humans and retail foods in China. This is likely due to the co-existence of genes carried by a multidrug resistance plasmid, and the plasmid can be transferred to other bacteria. These findings emphasized the importance of ongoing surveillance for the prevalence and transmission of this multidrug resistance plasmid in S. Indiana to better understand the potential threat to public health and to develop control strategies.
Technical Abstract: Salmonellosis is an important global foodborne disease, and Salmonella isolates that are resistant to a wide variety of antibiotics have become a major public health concern. The aim of this study was to investigate the distribution and transmission of mphA gene in azithromycin-resistant Salmonella isolates and characterize the plasmid bearing mphA. In this study, the azithromycin resistance was shown in 15 Salmonella enterica serovar Indiana (S. Indiana) isolates from chicken, duck and humans with concurrent resistance to ciprofloxacin and ceftriaxone, and two chicken-borne isolates of which were resistant to all antibiotics tested except colistin and imipenem. MLST and PFGE results suggested that these 15 isolates were closely related in phylogeny. The azithromycin resistance gene (mphA), extended-spectrum beta-lactamase (ESBL)-encoding genes (blaCTX-M-65, blaCTX-M-14 and blaCTX-M-15) and plasmid-mediated quinolone resistance (PMQR) genes [oqxAB, qepA, qnrA and aac(6')-Ib-cr] with mutations in the quinolone resistance determining region (QRDR) (gyrA and parC) were identified in these S. Indiana isolates. Plasmid conjugation and transformation were performed in these 15 isolates. The co-existence of the mphA gene with oqxAB-blaCTX-M-65 was observed on the IncHI2 plasmid with a size of~240 kbp in 7 transformants, and these 7 transformants exhibited the resistance to azithromycin (MIC from 32 µg/mL to 64 µg/mL) and ceftriaxone (MIC= 256 µg/mL). The complete sequence of an IncHI2 type plasmid, p13520, was determined. An approximately 80-kbp of multidrug resistance region (MRR) comprising 29 antimicrobial resistance genes (ARGs) including mphA, oqxAB, blaCTX-M-65, fosA3 and rmtB interspersed with different insertion sequences (IS)s (IS26, ISAba1, IS91, IS1006 and IS903B) was located on the plasmid. The typical IS26-mphA-mrx-mphR-IS6100 transposable structure was identified in the IncHI2 plasmid of nine transformants via genome sequencing and PCR mapping, which suggested that azithromycin resistance in S. Indiana was probably due to the dissemination of the IncHI2 plasmid carrying the mphA-mrx-mphR cluster. This study highlighted the emergence of S. Indiana with concurrent resistance to azithromycin, ciprofloxacin and ceftriaxone in humans and retail foods in China. This is likely due to the co-existence of mphA, oqxAB and blaCTX-M-65 carried by the IncHI2 plasmid. These findings emphasized the importance of ongoing surveillance for the prevalence and transmission of the p13520-like plasmid in S. Indiana, so as to better understand the potential threat to public health.