High Prevalence and Diversity Characteristics of blaNDM, mcr, and blaESBLs Harboring Multidrug-Resistant Escherichia coli From Chicken, Pig, and Cattle in China

Abstract

The objective of this study was to understand the diversity characteristics of ESBL-producing Escherichia coli (ESBL-EC) in chicken, pig, and cattle. A high prevalence of ESBL-EC (260/344) was observed in all food animals with prevalence rates of 78.6% (110/140) for chicken, 70.7% (58/82) for cattle, and 75.4% (92/122) for swine. However, the resistance rates presented significant differences in different animal origin ESBL-EC, where resistance to CTX, GEN, IMP, NEO, and OFL was the highest in chicken ESBL-EC, then in cattle, and the lowest in swine. Seriously, most ESBL-EC harbor multidrug resistance to antibiotics (MDR, ≥3 antibiotic categories), and the MDR rates of ESBL-EC were the highest in chicken (98.18%), followed by swine (93.48%), and the lowest in cow (58.62%), while the same trend also was observed in MDR of ≥5 antibiotic categories. This high prevalence and resistance can be partly interpreted by the high carriage rates of the β-lactamases CTX-M (n = 89), OXA (n = 59), SHV (n = 7), and TEM (n = 259). A significant difference of β-lactamase genes also presented in different animal species isolates, where the chicken origin ESBL-EC possessed higher carriage rates of almost all genes tested than cattle and swine. Notably, eight chicken origin ESBL-EC carried transferable plasmid-mediated blaNDM-1 or blaNDM-5, especially, of which four ESBL-EC also contained the colistin resistance gene mcr-1, as confirmed by genomic analysis. More interestingly, two deletion events with a 500-bp deletion in ΔISAba125 and a 180-bp deletion in dsbC were observed in three blaNDM-5 IncX3 plasmids, which, as far as we know, is the first discovery. This showed the instability and horizontal transfer of blaNDM genetic context, suggesting that blaNDM is evolving to “pack light” to facilitate rapid and stable horizontal transfer. Sequence types (STs) and PFGE showed diversity patterns. The most prevalent STs were ST48 (n = 5), ST189 (n = 5), ST206 (n = 4), ST6396 (n = 3), ST10 (n = 3), and ST155 (n = 3), where ST48 ESBL-EC originated from three food animal species. The STs of all blaNDM-positive ESBL-EC were attributed to three STs, namely, ST6396 (n = 2), ST206 (n = 2), and ST189 (n = 4), where ST189 was also the unique type for four mcr-1-carrying ESBL-EC. In conclusion, we suggest that the three animal species ESBL-EC show similar high prevalence, diversity in isolate lineages, and significant discrepancies in antibiotic resistance and resistance genes. This suggests that monitoring and anti-infection of different food animal origin ESBL-EC need different designs, which deserves more attention and further surveillance.

Global prevalence, characteristics, and future prospects of IncX3 plasmids: A review

“…The majority of the strains have the conserved structure “ bla NDM - ble MBL -trpF-dsbC,” but some simply have the “ bla NDM - ble MBL -trpF” structure, or the dsbC was changed into the dcbD “ bla NDM - ble MBL -trpF-dcbD,” and only two strains carrying bla NDM-5 had the conserved sequence” bla NDM - ble MBL -trpT-dcbD.” This conserved sequence may play a key role in stability and retention, increasing the transfer of ARGs and improving enzyme activity. However, the specific functions of related genes need to be investigated further ( Brinkac et al, 2019 ).In addition, the environment surrounding bla NDM contains not only conserved sequences but also mobile elements such as ISAba125, IS3000, IS5, and IS26, indicating that bla NDM acts as an external gene to recombine into the IncX3 plasmid by insertion or transposition depending on IS elements ( Liu et al, 2021b ). Meanwhile, IS26 is linked to bla SHV , bla KPC to ISKpn6 and ISKpn7, bla NDM to ISAba125 ( Sun et al, 2019 ), bla OXA-181 to IS26 and ISEcp1 ( Supplementary material ).…”

“…The findings confirm the potential of IncX3 plasmid for accumulating resistance genes via IS-mediated transposition, with the likely consequence of limiting effective treatment options for possible human infections. In bla NDM -carrying IncX3 plasmids, deletion events with a 500-bp deletion in ISAba125 and a 180-bp deletion in dsbC were observed, which is significant and powerful evidence that ISAba125 and dsbC were unstable, implying that bla NDM is evolving to reduce the burden to facilitate rapid and stable horizontal transfer ( Liu et al, 2021b ).…”

“…However, the specific functions of related genes need to be investigated further (Brinkac et al, 2019). In addition, the environment surrounding bla NDM contains not only conserved sequences but also mobile elements such as ISAba125, IS3000, IS5, and IS26, indicating that bla NDM acts as an external gene to recombine into the IncX3 plasmid by insertion or transposition depending on IS elements (Liu et al, 2021b). Meanwhile, IS26 is linked to bla SHV , bla KPC to ISKpn6 and ISKpn7, bla NDM to ISAba125 (Sun et al, 2019), bla OXA-181 to IS26 and ISEcp1 (Supplementary material).…”

Nasal carriage of CTX-M-55-producing Escherichia coli ST8369 in a healthy cohort in the city of Yangzhou, China

“…As a variant of bla CTX-M-15 , bla CTX-M-55 was first reported in clinical E. coli and K. pneumoniae isolates in Thailand in 2007 ( Kiratisin et al., 2007 ). Recently, bla CTX-M-55 has become the predominant CTX-M genotype in E. coli and Salmonella from food animals, food products, and patients in China ( Rao et al., 2014 ; Zhang et al., 2014 ; Fu et al., 2020 ; Huang et al., 2020 ; Liu et al., 2022 ; Zeng et al., 2022 ). One novel bla CTX-M variant bla CTX-M-252 was identified in this study.…”

Characterization of Extended-Spectrum β-Lactamase-Producing Escherichia coli Isolates That Cause Diarrhea in Sheep in Northwest China

“…In recent years, the rapid increase in animal infections, especially with pathogenic bacteria, due to extended-spectrum cephalosporin resistance is particularly worrisome ( 12 ). The prevalences of ESBL-producing E. coli have been reported to be 78.6% in chicken, 70.7% in cattle, and 75.4% in swine ( 13 , 14 ). Moreover, birds and dolphins might also play a key role in the development and intercontinental dissemination of ESBLs ( 15 , 16 ).…”