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. 2020 Dec 22:11:604710.
doi: 10.3389/fmicb.2020.604710. eCollection 2020.

Plasmid Dynamics of mcr-1-Positive Salmonella spp. in a General Hospital in China

Jianzhong Fan  1 , Linghong Zhang  2   3   4 , Jintao He  2   3   4 , Maoying Zhao  5 , Belinda Loh  6 , Sebastian Leptihn  2   6 , Yunsong Yu  2   3   4 , Xiaoting Hua  2   3   4
Affiliations

Plasmid Dynamics of mcr-1-Positive Salmonella spp. in a General Hospital in China

Jianzhong Fan et al. Front Microbiol. .

Abstract

Salmonella is an important food pathogen that can cause severe gastroenteritis with more than 600,000 deaths globally every year. Colistin (COL), a last-resort antibiotic, is ineffective in bacteria that carry a functional mcr-1 gene, which is often spread by conjugative plasmids. Our work aimed to understand the prevalence of the mcr-1 gene in clinical isolates of Salmonella, as the frequency of occurrence of the mcr-1 gene is increasing globally. Therefore, we analyzed 689 clinical strains, that were isolated between 2009 and late 2018. The mcr-1 gene was found in six strains, which we analyzed in detail by whole genome sequencing and antibiotic susceptibility testing, while we also provide the clinical information on the patients suffering from an infection. The genomic analysis revealed that five strains had plasmid-encoded mcr-1 gene located in four IncHI2 plasmids and one IncI2 plasmid, while one strain had the chromosomal mcr-1 gene originated from plasmid. Surprisingly, in two strains the mcr-1 genes were inactive due to disruption by insertion sequences (ISs): ISApl1 and ISVsa5. A detailed analysis of the plasmids revealed a multitude of ISs, most commonly IS26. The IS contained genes that meditate broad resistance toward most antibiotics underlining their importance of the mobile elements, also with respect to the spread of the mcr-1 gene. Our study revealed potential reservoirs for the transmission of COL resistance and offers insights into the evolution of the mcr-1 gene in Salmonella.

Keywords: IS; ISApl1; ISVsa5; Salmonella; inactivation; mcr-1.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Scaled, linear diagrams comparing the sequences of plasmid pSH16G4918 (GenBank no. MK477619), pS438, pS441, pS520, and pS585_1. Antibiotic resistance genes are indicated in red arrows. The individual conjugation-related genes are indicated with black arrows. Blue arrows denote transposon- and integron-associated genes. Other genes are shown as gray arrows.
FIGURE 2
FIGURE 2
Scaled, linear diagrams comparing the sequences between plasmid pS304_2, p1106-IncI2 (GenBank no. MG825374.1), pAH62-1 (GenBank no. CP055260.1), p2018-10-2CC (GenBank no. LC511622.1), pD90_2 (GenBank no. CP022452.1), and pSal-5091_MCR64k (GenBank no. CP045521.1). Antibiotic resistance genes are indicated in red arrows. The individual conjugation-related genes are indicated with black arrows. Blue arrows denote transposon- and integron-associated genes. Other genes are shown as gray arrows.
FIGURE 3
FIGURE 3
Scaled, linear diagrams comparing the sequences of S530, plasmid pS441, and pS520_1. Insertion elements are shown as green arrows. Genes, including antibiotic resistance genes, are shown as labeled red arrows. Flags indicate the 8 bp target site duplications (TSDs).
FIGURE 4
FIGURE 4
Scaled, linear diagrams comparing the sequences between S530, D90 (GenBank no. CP022450), and pMCR_WCHEC050613 (GenBank no. CP019214). Antibiotic resistance genes are indicated in red arrows. The inserted gene aaeR is marked as the green arrow. Blue arrows denote transposon- and integron-associated genes. Other genes are shown as gray arrows.
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