The prevalent characteristics of blaNDM-carrying E. coli

Totally, 33,055 E. coli isolates were downloaded from NCBI database and the time span was from 2003 to 2022. Of which, 1,774 were identified to be positive for the blaNDM gene (Additional file 1). These isolates were obtained from 43 countries across 6 continents (Fig. 1), which were as follows: Asia (n = 1376, 77.6%), Europe (n = 196, 11.0%), North America (n = 63, 3.6%), Africa (n = 29, 1.6%), South America (n = 29, 1.6%), and Oceania (n = 2, 0.1%). Of concern, China (n = 1127, 63.5%), India (n = 115, 6.5%), and France (n = 83, 4.7%) were the primary contributors, submitting the highest number of genomes, following closely were the USA (n = 56), Germany (n = 33), Thailand (n = 30), United Kingdom (n = 21), Bangladesh (n = 20), South Korea (n = 19), Lebanon (n = 16), and Pakistan (n = 11). The origin of the remaining 79 isolates was unspecified.

Fig. 1

Geographical distribution of blaNDM and STs of blaNDM-carrying Escherichia coli worldwide. Hollow and solid pie charts of each continent represent blaNDM and STs, respectively

Of 1,774 blaNDM genes, 15 distinct blaNDM variants were identified. While the number of blaNDM-carrying E. coli showed a gradual increase each year, it surged significantly in 2015 (n = 350). This elevated level was sustained from 2016 to 2019, followed by a decline from 2020 to 2022 (Fig. 2).

Fig. 2

Number of global blaNDM-carrying Escherichia coli isolates submitted per year

Regarding the sources of the blaNDM-carrying E. coli isolates (Table 1), it was observed that Homo sapiens accounted for the majority, constituting 59.6% (n = 1,057) of the total. These isolates were predominantly sourced from urine (n = 232), blood (n = 162), rectal/anal swabs (n = 149), sputum (n = 81), and fecal samples (n = 86). Animals comprised 27.4% (n = 486) of the isolates, with chickens (n = 182), pigs (n = 59), and flies (n = 46) being the most prevalent species. The primary sources for animal isolates included fecal samples, cloaca swabs, and various organs (intestine/liver/other). Notably, blaNDM-carrying strains were also detected in the environment, accounting for 13.0% (n = 231) of the isolates. These environmental sources included water, hospitals, and various food items.

Table 1 The hosts and sample types of global blaNDM-carrying E. coli isolatesWide distribution of various resistance genes among blaNDM-carrying E. coli

Among the 1,774 blaNDM-carrying isolates, 15 distinct variants were identified, with blaNDM-5 being the most prevalent (n = 1,315, 74.1%), followed by blaNDM-1 (n = 295, 16.6%) and blaNDM-9 (n = 82, 4.6%). Other variants included blaNDM-7, blaNDM-4, blaNDM-6, blaNDM-13, blaNDM-3, blaNDM-15, blaNDM-19, blaNDM-16, blaNDM-20, blaNDM-21, blaNDM-22, and blaNDM-24, each with lower frequencies. Geographically, blaNDM-5 dominated in Asia, Europe, Africa, and North America, constituting 62.0-77.0% of cases (Fig. 1). Notably, South America exhibited a distinct pattern, with blaNDM-1 being the most common variant, representing 93.0% of cases.

A comprehensive analysis of ARGs in blaNDM-carrying strains revealed 213 different types. Among them, CHßLs encoding genes including 8 blaKPC-2, 1 blaIMP-1, 34 blaOXA-181, 10 blaOXA-232, 5 blaOXA-244 and 5 blaOXA-48 were identified. Moreover, 27 blaCTX-M and 39 blaTEM variants were detected with blaCTX-M-15 (n = 438, 24.7%), blaCTX-M-55 (n = 300, 16.9%), blaCTX-M-14 (n = 204, 11.5%), blaCTX-M-65 (n = 147, 8.3%) and blaTEM-1B (n = 1092, 61.6%) being the most frequent ones, respectively. In addition, 546 (30.8%) plasmids mediated ampC genes, including 501 blaCMY and 45 blaDHA as well as 508 (28.6%) 16S-RMTase encoding genes, including 409 rmtB, 55 rmtC and 44 armA were found. Of significant concern, 262 (14.8%) co-existing mcr genes were also detected, with mcr1.1 being the most prevalent genotype (n = 249, 14.0%). Furthermore, 467 (26.3%) fosfomycin resistance genes including 459 fosA3 and 8 fosA4 as well as 546 (30.8%) aac(6’)-ib-cr conferring resistance to amikacin and fluoroquinolones in addition to 805 (45.4%) PMQRs including 239 oqxAB, 126 qepA, and 440 qnr were identified. Other main ARGs detected were shown in Fig. 3.

Multiple distinct sequence types were identified with several high-risk clones being prevalent

A total of 232 distinct STs were identified among the blaNDM-carrying E. coli isolates. The most prevalent was ST167 (n = 306, 17.2%), followed by ST410 (n = 174, 9.8%), ST361 (n = 108, 6.1%), ST405 (n = 85, 4.8%), ST156 (n = 74, 4.2%), ST10 (n = 73, 4.1%), ST48 (n = 59, 3.3%), ST617 (n = 53, 3.0%), ST101 (n = 50, 2.8%), ST648 (n = 44, 2.5%), and ST746 (n = 38, 2.1%). Several other STs were also identified, with each less than 30. Geographically, the distribution of STs varied. ST167 was predominant in both Asia and North America, ST361 was endemic in Europe, and ST410 emerged as the predominant clone in Africa, with ST10 dominating in South America (Fig. 1).

Fig. 3

The antimicrobial resistance genes identified among 1774 blaNDM-carrying Escherichia coli. 3 A. all the antimicrobial resistance genes; 3B. mcr variants; 3 C, blaOXA variants; 3D. blaCMY variants; 3E. blaNDM variants; 3 F. blaCTX-M variants; 3G. blaTEM variants

Virulence factors

A total of 170 distinct VFs were identified among the blaNDM-carrying E. coli isolates. The most prevalent VF was terC (n = 1,766, 99.5%). Notably, more than half of the isolates carried four specific VFs: gad (83.4%, n = 1,480), traT (67.9%, n = 1,205), and iss (51.3%, n = 910). Several other VFs were also frequently detected, including sitA (n = 756, 42.6%), hra (n = 689, 38.8%), lpfA (n = 631, 35.6%), fyuA (n = 561, 31.6%), and irp2 (n = 560, 31.6%).

Of significant concern is the differential distribution of the predominantly prevalent VFs among the endemic clones. Notably, lpfA was primarily distributed among ST410 and ST156, while iss was predominantly concentrated in ST167 and ST156. The dominance of fyuA and irp2 was observed among ST405, with ST361 and ST405 being the most frequent carriers for sitA.

Multiple Plasmid replicons were found among blaNDM-carrying E. coli which may facilitate the spread of antimicrobial resistance genes

Various plasmid replicons were identified, with IncFII (n = 1,163, 65.6%) emerging as the most prevalent. Following closely were IncFIB (n = 1,157, 65.2%), IncX3 (n = 888, 50.1%), IncFIA (n = 756, 42.6%), COL (n = 440, 24.8%), IncY (n = 338, 19.1%), IncI1-I (n = 321, 18.1%), P0111 (n = 306, 17.2%), IncHI2 (n = 287, 16.2%), IncQ1 (n = 194, 10.9%), IncI (n = 190, 10.7%), IncFIC (n = 179, 10.1%), IncC (n = 174, 9.8%), IncR (n = 114, 6.4%), IncX1 (n = 128, 7.2%), IncN (n = 77, 4.3%), and several other rare plasmid replicons.

Analysis revealed that 44.7–66.8% of blaNDM-5-carrying strains carried IncFII, IncFIB, IncX3, and IncFIA plasmids (Table 2). For blaNDM-1-carrying strains, over half carried IncFII and IncFIB plasmids, with IncFIA and Col being relatively highly prevalent. IncFIB, IncFII, and Col were frequently carried by blaNDM-9 positive strains. Notably, IncFIA was particularly prevalent, reaching 80.9%, in blaNDM-7-carrying strains, followed by IncFIB, IncFII, and IncX3.

Table 2 Plasmids distribution among different blaNDM-carrying strains

Analyzing the consistency between prevalent plasmids and resistant/virulent genes (Table 3) revealed correlations between the prevalence of mph(A) and tra(T) and the plasmid replicons IncFII and IncFIB (p > 0.05). The incidences of aph(6)-Id, aadA2, aph(3’’)-Ib, dfrA12, and iss were all correlated with the presence of plasmid IncX3. Additionally, the distribution of blaOXA-1, iucC, and capU was consistent with the presence of plasmid Col.

Table 3 Consistency analysis between plasmids and resistant/virulent genes

The prevalence of ARGs and VFs among epidemic clones ST167, ST410, ST361, ST405 and ST156 were demonstrated in the Fig. 4. More than 42.5% of them carried blaTEM, blaCTX-M, blaNDM-5, traT, gad and terC, constituting a basic resistant and virulent profile. In detail, ST167 clones exhibited high incidences of iss and hra; S156 showed a high carriage of mcr, rmt, lpdA, iss, and hra. Notably, ST410 clones demonstrated nearly 100% carriage of lpfA and high incidences of aac(6’)-ib-cr and blaOXA, while ST405 showed a high prevalence of fyuA, irp2, sitA, traT, gad and rmt. This highlights the distinct prevalence patterns of ARGs among different STs, emphasizing the diversity in resistance and virulence profiles associated with specific E. coli lineages.

Fig. 4

The prevalence of prevalent antimicrobial resistance genes and virulent factors among epidemic clones. Antimicrobial resistance genes were aac(6’)-ib-cr, mcr, rmt, qnr, blaOXA, blaTEM, blaCTX-M, blaNDM-5; Virulence factors were terC, gad, traT, iss, sitA, hra, lpfA, fyuA, irp2

A large number of serotypes detected among blaNDM-carrying E. coli with O101:H9 and O8:H9 being the predominate

A total of 91 distinct O types were identified, with O101 (n = 391, 22.0%), O8 (n = 179, 10.1%), O9 (n = 154, 8.7%), and O102 (n = 92, 5.2%) emerging as the dominant ones. Among the 43 H types, H9 (n = 470, 26.5%) was the most prevalent, followed by H30 (n = 140, 7.9%), H6 (n = 130, 7.3%), H10 (n = 121, 6.8%), and H5 (n = 114, 6.4%). Over 100 distinct serotypes were identified, with O101:H9 (n = 231, 13.0%), O8:H9 (n = 115, 6.5%), O9:H30 (n = 99, 5.6%), O102:H6 (n = 86, 4.8%), and O101:H10 (n = 77, 4.3%) being the most frequent.