Epidemic IncX3 plasmids spreading carbapenemase genes in the United Arab Emirates and worldwide

Figures & data

Table 1 Distribution of IncX3 plasmid carrying isolates among strains expressing different carbapenem resistance mechanisms

n	All	NDM	OXA-48-like	NDM and OXA-48-like	VIM	KPC	All carbapenemase producer	Carbapenemase non-producer
	334	89	126	75	3	2	295	39
IncX3 PCR positive	32 (9.6%)	18 (20%)	6 (4.8%)	4 (5.3%)	0	2 (100%)	30 (10.2%)	2 (5.1%)

Table 2 Characteristics of carbapenemase producing Enterobacteriaceae harboring IncX3 type plasmids with carbapenemase genes

Isolate							Plasmid					Ref.
Name*	Date of isolation	Hospital	Specimen	Species	Carbapenemase produced	MLST	C/Cm/nonC	Name	Size (bp)	Resistance gene(s)	GenBank Acc. No
ABC133	12/14/2012	TH	Sputum	E. coli	NDM-7	ST4108	nonC	pABC133-NDM	37070	blaNDM-7	KX214671	^Citation24
ABC239	8/15/2013	RH	Urine	E. coli	OXA-181	ST410	nonC	pABC239-OXA-181	51479	blaOXA-181+ qnrS1	MK412916	This study
ABC264	6/9/2014	TH	Unknown	E. coli	OXA-181	ST410	nonC	pABC264-OXA-181	51479	blaOXA-181+ qnrS1	MK412917	This study
ABC356	8/8/2014	MH	Urine	E. coli	OXA-181	ST410	Cm	pABC356-OXA-181	51479	blaOXA-181+ qnrS1	MK412918	This study
ABC381	11/4/2014	AAH	Rectal swab	E. coli	OXA-181	ST167	nonC	pABC381-OXA-181	51479	blaOXA-181+ qnrS1	MK412919	This study
ABC218	12/25/2012	RH	Wound	E. coli	NDM-7	ST167	C	pABC218-NDM	34403	blaNDM-7	KX214670	^Citation24
ABC233	7/21/2013	RH	Urine	E. coli	NDM-5	ST167	Cm	pABC233-NDM-5	46161	blaNDM-5	MK372390	This study
ABC384	11/5/2014	AAH	Urine	E. coli	NDM-5	ST1284	C	pABC384-NDM-5	46161	blaNDM-5	MK372389	This study
ABC54	1/2/2011	TH	Urine	E. coli	NDM-1	ST2206	C	pABC54-NDM-1	53023	blaNDM-1+ blaSHV-12	MK372382	This study
BC-13-836	9/24/2013	TH	Blood	E. coli	NDM-1	ST446	C	pBC836-NDM-1	52565	blaNDM-1+ blaSHV-11	MK372387	This study
ABC280	7/15/2014	TH	Urine	E. coli	NDM-5	ST448	C	pABC280-NDM5	35502	blaNDM-5	MK372392	This study
ABC286	8/15/2014	TH	Blood	E. coli	NDM-5	ST448	NT	NT	NT	NT	NT	This study
ABC268	6/11/2014	AAH	Urine	E. coli	NDM-5	ST2083	Cm	pABC268-NDM-5	45232	blaNDM-5	MK372391	This study
ABC40	10/27/2009	TH	Wound	E. cloacae	NDM-1	ST417	Cm	pABC40-NDM-1	54035	blaNDM-1+ blaSHV-12	MK372380	This study
ABC302	2/26/2014	MH	Urine	E. cloacae	NDM-4	ST200	C	ABC302-NDM-4	49402	blaNDM-4	MK372388	This study
BC-13-947	7/11/2013	TH	Blood	K. pneumoniae	OXA-181	ST2095	nonC	pBC947-OXA-181	51479	blaOXA-181+ qnrS1	MK412920	This study
ABC260	3/31/2014	TH	Rectal swab	K. pneumoniae	OXA-181	ST3545	nonC	pABC260-OXA-181	51480	blaOXA-181+ qnrS1	MK412915	This study
ABC369	9/23/2014	TH	Abdominal fluid	K. pneumoniae	NDM-5+ OXA-162	ST307	Cm	pABC369-NDM-5	45252	blaNDM-5	MK372393	This study
ABC137	1/14/2013	MH	Wound	K. pneumoniae	NDM-1+ OXA-48	ST1318	Cm	pABC137-NDM-1	53022	blaNDM-1+ blaSHV-12	MK372384	This study
ABC141	4/20/2013	MH	Unknown	K. pneumoniae	NDM-1+ OXA-48	ST1318	NT	NT	NT	NT	NT	This study
ABC155	6/5/2013	SKMC	Blood	K. pneumoniae	NDM-1+ OXA-48	ST1318	NT	NT	NT	NT	NT	This study
ABC220	10/5/2012	RH	Wound	K. pneumoniae	KPC-2	ST14	C^#	pABC220-KPC-2	46900	blaKPC-2	MK412914	This study
ABC224	3/17/2013	RH	Sputum	K. pneumoniae	KPC-2	ST14	C^#	NT	NT	NT	NT	This study
ABC52	9/19/2010	TH	Sputum	K. pneumoniae	NDM-1	ST11	C	pABC52-NDM-1	52565	blaNDM-1+ blaSHV-12	MK372381	This study
ABC53	9/19/2010	TH	Sputum	K. pneumoniae	NDM-1	ST11	NT	NT	NT	NT	NT	This study
BC680	7/18/2012	TH	Blood	K. pneumoniae	NDM-1	ST11	NT	NT	NT	NT	NT	This study
BC700	7/24/2012	TH	Blood	K. pneumoniae	NDM-1	ST11	C	pBC700-NDM-1	52565	blaNDM-1+ blaSHV-11	MK372386	This study
BC-13-817	9/17/2013	TH	Blood	K. pneumoniae	NDM-1	ST11	NT	NT	NT	NT	NT	This study
ABC80	5/8/2011	TH	Urine	Citrobacter freundii	NDM-1	NT	Cm	pABC80-NDM-1	53023	blaNDM-1+ blaSHV-12	MK372383	This study
ABC140	3/25/2013	MH	Perianal swab	Morganella morganii	NDM-1	NA	nonC	pABC140-NDM-1	52591	blaNDM-1	MK372385	This study

Notes: *Strain names with bold indicate those from which the IncX3 plasmid was fully sequenced in this study.

Abbreviations: MLST, Multi-Locus Sequence Typing; ST, sequence type; NA, not applicable; NT, not tested; C, conjugative; Cm, conjugative with transconjugants having multiple plasmids; C^#, conjugative, but cannot stably maintained in E. coli J53_RAZ; nonC, not self-transmissible.

Figure 1 Comparison of IncX3 plasmids from the United Arab Emirates carrying various carbapenemases.

Notes: Grey shades represent regions with ≥99% similarity.

Figure 2 Phylogenetic tree of backbone sequences of IncX3 plasmids from various geographical area.

Notes: The sequences were aligned using ClustalW, and the Neighbor-Joining tree was constructed using the Jukes-Cantor genetic distance model with 500 bootstrap replicates. All positions containing gaps and missing data were eliminated. There was a total of 24,868 positions in the final dataset. Plasmid names printed in bold represent IncX3 plasmids from the UAE, for plasmids retrieved from GenBank the accession number, the beta-lactamase gene carried, and the country of isolation is shown.

Abbreviations: CA, Canada; CH, Switzerland; CN, China; CZ, Czech Republic; DN, Denmark; FR, France; GR, Germany; HK, Hong Kong; IN, India; IT, Italy; KR, South Korea; KW, Kuwait; LB, Lebanon; MY, Myanmar; NL, the Netherlands; OM, Oman; US, United States of America.

Figure S1 (A) Comparison of pulsed-field gel electrophoresis patterns of Escherichia coli isolates. (B) Comparison of pulsed-field gel electrophoresis patterns of Klebsiella pneumoniae isolates.

Table S1 Antibiotic susceptibility of clinical isolates carrying carbapenemases on IncX3 plasmids and their single IncX3 plasmid containing derivatives

Strain	Carbapenemase produced	Wild type/transconjugant/transformant	Ertapenem	Imimpenem	Meropenem	Ceftazidime	Cefotaxime	Aztreonam	Ciprofloxacin	Gentamicin	Amikacin	Co-trimoxazole	Tetracycline	Colistin	Tigecycline	Fosfomycin
ABC220	KPC-2	WT	256	64	128	>128	>128	>128	64	256	16	>256	4	32	0.5	256
GM3163(pABC220-KPC-2)	KPC-2	TF	4	4	2	16	4	>128	≤0.125	1	1	≤0.5	≤0.5	≤0.5	≤0.125	16
ABC224	KPC-2	WT	256	64	128	>128	>128	>128	32	256	32	>256	4	32	0.5	128
ABC140	NDM-1	WT	2	32	8	128	32	4	8	2	4	≤0.5	16	>256	4	>512
DH5α(pABC140-NDM-1)	NDM-1	TF	0.5	2	≤0.25	>128	64	32	≤0.125	≤0.5	2	≤0.6	≤0.5	≤0.5	≤0.125	≤0.25
ABC40	NDM-1	WT	32	16	16	>128	>128	>128	>64	128	4	≤0.7	256	2	1	8
J53RAZ(pABC40-NDM-1)	NDM-1	TC	0.25	4	4	>128	64	32	≤0.125	≤0.5	≤0.5	≤0.8	≤0.5	≤0.5	≤0.125	0.5
ABC52	NDM-1	WT	64	32	64	>128	>128	>128	>64	>256	>256	>256	4	≤0.5	1	4
J53RAZ(pABC52-NDM-1)	NDM-1	TC	1	4	8	>128	64	64	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	1
ABC53	NDM-1	WT	64	64	64	>128	>128	>128	>64	>256	>256	>256	4	≤0.5	2	16
ABC54	NDM-1	WT	8	16	16	>128	128	>128	0.25	1	4	>256	128	≤0.5	0.25	0.5
DH5α(pABC54-NDM-1)	NDM-1	TF	0.25	4	4	>128	64	32	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	0.5
ABC80	NDM-1	WT	8	8	4	>128	128	>128	4	32	1	128	≤0.5	≤0.5	0.25	0.5
J53RAZ(pABC80-NDM-1)	NDM-1	TC	0.5	8	4	>128	64	32	≤0.125	1	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	0.5
BC680	NDM-1	WT	16	32	64	>128	>128	>128	>64	4	16	>256	2	≤0.5	2	4
BC700	NDM-1	WT	16	64	32	>128	>128	>128	>64	2	16	>256	2	≤0.5	2	4
J53RAZ(pBC700-NDM-1)	NDM-1	TC	2	4	4	>128	64	≤0.25	≤0.125	1	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	0.5
BC-13-817	NDM-1	WT	16	32	32	>128	>128	>128	>64	4	16	>256	2	≤0.5	2	4
BC-13-836	NDM-1	WT	4	16	16	>128	>128	≤0.25	≤0.125	2	4	≤0.5	128	≤0.5	≤0.125	0.5
DH5α(pBC836-NDM-1)	NDM-1	TF	0.25	2	≤0.25	>128	64	≤0.25	≤0.125	≤0.5	1	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
ABC141	NDM-1+ OXA-48	WT	16	64	32	>128	>128	>128	>64	128	8	>256	>256	4	16	8
ABC155	NDM-1+ OXA-48	WT	>256	>128	>128	>128	>128	>128	4	128	4	>256	>256	≤0.5	2	128
ABC137	NDM-1+ OXA-48	WT	16	64	32	>128	>128	>128	4	128	4	>256	>256	≤0.5	2	8
J53RAZ(pABC137-NDM-1)	NDM-1	TC	0.25	4	4	>128	64	32	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	0.5
ABC302	NDM-4	WT	128	64	128	>128	>128	>128	64	>256	>256	>256	8	≤0.5	2	16
DH5α(pABC302-NDM-4)	NDM-4	TF	0.25	2	≤0.25	>128	64	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
ABC233	NDM-5	WT	32	16	32	>128	>128	>128	>64	>256	>256	128	1	≤0.5	≤0.125	0.5
DH5α(pABC233-NDM-5)	NDM-5	TF	0.5	2	≤0.25	>128	64	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
ABC268	NDM-5	WT	32	16	32	>128	>128	32	>64	64	4	256	1	≤0.5	0.25	1
DH5α(pABC268-NDM-5)	NDM-5	TF	0.25	2	≤0.25	>128	64	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
ABC280	NDM-5	WT	32	16	16	>128	>128	>128	>64	64	8	>256	1	≤0.5	0.25	1
J53RAZ(pABC280-NDM-5)	NDM-5	TC	0.5	4	8	>128	128	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	1
ABC286	NDM-5	WT	64	8	32	>128	>128	>128	>64	32	4	256	1	≤0.5	0.25	1
ABC384	NDM-5	WT	64	128	32	>128	>128	>128	>64	64	8	256	>256	≤0.5	≤0.125	0.5
J53RAZ(pABC384-NDM-5)	NDM-5	TC	0.25	4	4	>128	64	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	1
ABC369	NDM-5+ OXA-162	WT	4	8	8	>128	>128	>128	>64	256	>256	>256	4	≤0.5	2	4
DH5α(pABC369-NDM-5)	NDM-5	TF	0.25	2	≤0.25	>128	64	≤0.25	≤0.125	≤0.5	1	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
ABC133ETP	NDM-7	WT	128	128	128	>128	>128	64	>64	64	8	≤0.5	>256	≤0.5	0.25	0.5
DH5α(pABC133-NDM)	NDM-7	TF	1	4	2	>128	64	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
ABC218	NDM-7	WT	64	16	32	>128	>128	>128	>64	256	8	256	1	≤0.5	≤0.125	0.5
J53RAZ(pABC218-NDM)	NDM-7	TF	2	8	8	>128	128	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	1
ABC239	OXA-181	WT	2	0.5	≤0.25	>128	>128	>128	>64	128	8	>256	>256	≤0.5	≤0.125	0.5
DH5α(pABC239-OXA-181)	OXA-181	TF	0.5	≤0.25	≤0.25	≤0.25	≤0.25	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
ABC260	OXA-181	WT	128	64	32	2	2	0.5	16	1	1	>256	4	16	2	>512
DH5α(pABC260-OXA-181)	OXA-181	TF	≤0.125	≤0.25	≤0.25	≤0.25	≤0.25	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
ABC264	OXA-181	WT	2	1	≤0.25	>128	>128	>128	>64	4	4	256	>256	≤0.5	0.25	1
DH5α(pABC264-OXA-181)	OXA-181	TF	≤0.125	≤0.25	≤0.25	≤0.25	≤0.25	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
ABC356	OXA-181	WT	2	1	0.5	>128	>128	>128	>64	128	8	>256	>256	≤0.5	0.25	0.5
DH5α(pABC356-OXA-181)	OXA-181	TF	0.25	≤0.25	≤0.25	≤0.25	≤0.25	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
ABC381	OXA-181	WT	16	8	8	>128	128	8	64	2	2	256	256	≤0.5	0.25	≤0.25
DH5α(pABC381-OXA-181)	OXA-181	TF	≤0.125	≤0.25	≤0.25	≤0.25	≤0.25	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
BC-13-936	OXA-181	WT	0.25	2	0.5	≤0.25	≤0.25	≤0.25	1	2	2	>256	1	≤0.5	0.25	16
BC-13-947	OXA-181	WT	≤0.125	2	0.5	16	2	64	1	2	2	>256	1	8	0.25	16
DH5α(pBC947-OXA-181)	OXA-181	TF	≤0.125	≤0.25	≤0.25	≤0.25	≤0.25	≤0.25	≤0.125	≤0.5	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
BC-13-970	OXA-181	WT	0.25	2	0.5	0.5	≤0.25	≤0.25	1	2	2	>256	1	≤0.5	0.25	16
DH5α	None	R	≤0.125	≤0.25	≤0.25	≤0.25	≤0.25	≤0.25	≤0.125	1	1	≤0.5	≤0.5	≤0.5	≤0.125	≤0.25
GM2163	None	R	≤0.125	≤0.25	≤0.25	≤0.25	≤0.25	≤0.25	≤0.125	2	4	≤0.5	≤0.5	≤0.5	≤0.125	16
J53Raz	None	R	≤0.125	≤0.25	≤0.25	≤0.25	≤0.25	≤0.25	≤0.125	1	≤0.5	≤0.5	≤0.5	≤0.5	≤0.125	0.5

Table S2 IncX3 plasmids (retrieved from GenBank in January 2019) from different geographical regions with unique backbone sequences and beta-lactamase genes carried

Resistance genes	Country	Name	GenBank Accession No
blaKPC-2	Hong Kong	pKPC-NY79	JX104759
blaNDM-17	China	pAD-19R	KX833071
blaNDM-4	Myanmar	pM216_X3	AP018146
blaNDM-4	Australia	pJEG027	KM400601
blaNDM-4	Czech Republic	pEncl-922cz	MG252892
blaNDM-5	Czech Republic	pEsco-5256cz	MG252891
blaNDM-5	India	pNDM-MGR194	KF220657
blaNDM-5	Hong Kong	pNDM-HK2998	MH234508
blaNDM-5	Hong Kong	pNDM-HK2967	MH234509
blaNDM-5	South Korea	pCREC-591_4	CP024825
blaNDM-7	South Korea	pCREC-532_3	CP024833
blaNDM-7	Oman	pOM26-NDM	KP776609
blaNDM-7	Kuwait	pKW53T-NDM	KX214669
blaNDM-7	Canada	pKpN01-NDM-7	CP012990
blaNDM-7	Myanmar	pM110-X3	AP018141
blaNDM-7	China	pEC50-NDM-7	KX470735
blaOXA-181	Italy	pKP_BO_OXA-181	MG228426
blaOXA-181, qnrS1	China	pOXA-181	KP400525
blaOXA-181, qnrS1	Switzerland	pKS22	KT05457
blaOXA-181, qnrS1	Germany	pOXA-181-IHIT35346	KX894452
blaOXA-181, qnrS1	South Korea	pD6-OXA_1_1	MG702491
blaOXA-181, qnrS1	Myanmar	pM206-OXA181	AP018831
blaOXA-181, qnrS1	Czech Republic	pOXA181_29144	KX523903
blaOXA-181, qnrS1	Lebanon	pSTIB_IncX3_OXA_181	MG570092
blaOXA-181, qnrS1	Denmark	pAMA1167-OXA-181	CP024806
blaSHV-11	Italy	pIncX-SHV	JN247852
blaSHV-11, blaKPC-3	Italy	p45-IncX3	KT362706
blaSHV-12	Netherlands	pEC-393	KX618697
blaSHV-12	Netherlands	pEC-125	KX618703
blaSHV-12, aac(6ʹ)-Ib	USA	pKPN-819	CP008799
blaSHV-12, blaKPC-2	France	pKpS90	JX461340
blaNDM-1+ blaSHV-12	China	pNDM-HN380	JX104760
blaNDM-1+ blaSHV-12	Hong Kong	pNDM-HK3694	MH234505
blaSHV-12, blaTEM-1, qnrS1	Netherlands	pEC-NRS18	KX618696
None	USA	pUCLAOXA232-2	CP012563

Pál T, Ghazawi A, Darwish D, et al. Characterization of NDM-7 carbapenemase-producing Escherichia coli isolates in the Arabian Peninsula. Microb Drug Resist. 2017;23:871–878. doi:10.1089/mdr.2016.006928156193

 PubMed Web of Science ®Google Scholar