Wide distribution of Escherichia coli carrying IncF plasmids containing bla NDM-5 and rmtB resistance genes from hospitalized patients in England

• Published in: Journal of medical microbiology Vol. 71; no. 8
• Main Authors: Turton, Jane F., Pike, Rachel, Perry, Claire, Jenkins, Claire, Turton, Jack A., Meunier, Danièle, Hopkins, Katie L
• Format: Journal Article
• Language: English
• Published: 12-09-2022
• ISSN: 0022-2615; 1473-5644
• DOI: 10.1099/jmm.0.001569

Introduction
. The New Delhi metallo-β-lactamase (NDM) variant NDM-5 was first described in 2011 in an isolate of
Escherichia coli
. We noted that a high proportion of isolates of
E. coli
positive for
bla
NDM
carbapenemase genes submitted to the UK Health Security Agency (formerly Public Health England) between 2019 and mid-2021 carried the
bla
NDM-5
allele, with many co-harbouring
rmtB
, rendering them highly resistant to aminoglycosides as well as to most β-lactams.
Hypothesis/Gap Statement
. This observation suggested that a common plasmid may be circulating.
Aim
. To compare these isolates and describe the plasmids carrying these resistance elements.
Methodology
. All isolates were sequenced on an Illumina platform, with five also subjected to long-read nanopore sequencing to provide complete assemblies. The locations of
bla
NDM-5
,
rmtB
and other associated genetic elements were identified. Susceptibility testing to a wide range of antibiotics was carried out on representative isolates.
Results
. The 34 isolates co-harbouring
bla
NDM-5
and
rmtB
were from 14 hospital groups and six different regions across England and consisted of 11 distinct sequence types. All carried IncF plasmids. Assembly of the NDM plasmids in five isolates revealed that they carried
rmtB
and
bla
NDM-5
in an IncF conjugative plasmid ranging in size from 85.5 to 161 kb. All carried a highly conserved region, previously described in
E. coli
plasmid pHC105-NDM, that included
bla
TEM-1B
and
rmtB
followed by sequence bounded by two IS
26
elements containing ΔIS
Aba125
,
bla
NDM-5
,
ble
,
trpF
and
tat
followed by IS
CR1
and an integron with
sul1
,
aadA2
and
dfrA12
cassettes. This arrangement has been described in isolates from other countries and continents, suggesting that such plasmids are widely distributed, at least in
E. coli
, with similar plasmids also found in
Klebsiella pneumoniae
. Tested isolates were resistant to most antibiotics except colistin, fosfomycin and tigecycline.
Conclusion
. These observations suggest that conjugative plasmids carrying a highly conserved resistance gene segment have become widespread in England and elsewhere. This study highlights the value of routine whole-genome sequencing in identifying genetic elements responsible for resistance dissemination.