TY - JOUR
T1 - Ambler class C-type β-lactamases and porin alterations in Enterobacter cloacae complex and Klebsiella aerogenes in the Netherlands, 2012–2023
AU - Van Gorp, Elke
AU - Lansu, Simon
AU - Wielders, Cornelia C. H.
AU - De Haan, Angela
AU - Godeke, Gert-Jan
AU - Witteveen, Sandra
AU - Bos, Jeroen
AU - Landman, Fabian
AU - Ouw, Maureen
AU - Wunderink, Herman F.
AU - Van Meer, Maurits P. A.
AU - Van Der Zwet, Wil
AU - Notermans, Daan W.
AU - Hendrickx, Antoni P. A.
AU - Van Arkel, A. L. E.
AU - Leversteijn-van Hall, M. A.
AU - Van Den Bijllaardt, W.
AU - Van Mansfeld, R.
AU - Van Dijk, K.
AU - Zwart, B.
AU - Diederen, B. M. W.
AU - Berkhout, H.
AU - Ott, A.
AU - Waar, K.
AU - Ang, W.
AU - Da Silva, J.
AU - Vlek, A. L. M.
AU - Stohr, J. J. J. M.
AU - Bode, L. G. M.
AU - Jansz, A.
AU - Paltansing, S.
AU - Van Griethuysen, A. J.
AU - Lo Ten Foe, J. R.
AU - Van Trijp, M. J. C. A.
AU - Wong, M.
AU - Muller, A. E.
AU - Van Der Linden, M. P. M.
AU - Van Rijn, M.
AU - Debast, S. B.
AU - Kolwijck, E.
AU - Al Naiemi, N.
AU - Schulin, T.
AU - Dinant, S.
AU - Van Mens, S. P.
AU - Melles, D. C.
AU - Stuart, J. W. T. Cohen
AU - Gruteke, P.
AU - Van Dam, A. P.
AU - Maat, I.
AU - Maraha, B.
AU - Et al.
PY - 2026/1/30
Y1 - 2026/1/30
N2 - We investigated the genomic epidemiology of Ambler class C (AmpC-type) β-lactamases in Enterobacter cloacae complex and Klebsiella aerogenes in the national carbapenemase-producing Enterobacterales (CPE) surveillance of the Netherlands between 2012 and 2023. A total of 399 E. cloacae complex and K. aerogenes isolates from 399 patients were analyzed using whole-genome sequencing to assess genetic relatedness, resistance genes, porin, and AmpC-regulatory gene profiles, plasmid replicons, and the genomic location of AmpC-genes, respectively. Of the 399 patients, 217 were male (54%), and the median age was 67 years. Carbapenemase production was assessed using the carbapenem inactivation method (CIM) and CarbaNP-test. A considerable proportion of E. cloacae complex (32%) and K. aerogenes (52%) isolates were CIM-positive in the absence of detectable carbapenemase genes (IMP, KPC, NDM, OXA-48-like, VIM) by the CarbaPCR, a phenotype termed CIM + Carba-. These isolates were mostly (81.9%) susceptible (EUCAST ≤ 2mg/L) to meropenem. The majority of CIM + Carba + isolates with major carbapenemase genes were gained from pre-emptive screening, while CIM + Carba- isolates were mainly taken for diagnostic purposes. Genomic analysis identified 18 genogroups, with E. kobei, E. roggenkampii, E. ludwigii, and K. aerogenes showing the CIM + Carba- phenotype, were mostly lacking porins and AmpC regulators, and correlated with chromosome-encoded AmpC-type β-lactamases like bla
ACT-28, bla
ACT-52,bla
MIR-3, bla
MIR-11 or ampC of which the majority (63%) yielded a positive CarbaNP-test. These CIM + Carba- isolates carried only few plasmids, and there was limited evidence of nosocomial spread. CIM + Carba- E. kobei carrying bla
ACT-28 overproduced ACT-28 protein in the CIM. Overall, the Enterobacter and K. aerogenes population in the Netherlands is genetically diverse, with most isolates carrying species-specific AmpC-type β-lactamases. Isolates with low MIC for meropenem that lack porins and major carbapenemases represent a low-risk for public health.
AB - We investigated the genomic epidemiology of Ambler class C (AmpC-type) β-lactamases in Enterobacter cloacae complex and Klebsiella aerogenes in the national carbapenemase-producing Enterobacterales (CPE) surveillance of the Netherlands between 2012 and 2023. A total of 399 E. cloacae complex and K. aerogenes isolates from 399 patients were analyzed using whole-genome sequencing to assess genetic relatedness, resistance genes, porin, and AmpC-regulatory gene profiles, plasmid replicons, and the genomic location of AmpC-genes, respectively. Of the 399 patients, 217 were male (54%), and the median age was 67 years. Carbapenemase production was assessed using the carbapenem inactivation method (CIM) and CarbaNP-test. A considerable proportion of E. cloacae complex (32%) and K. aerogenes (52%) isolates were CIM-positive in the absence of detectable carbapenemase genes (IMP, KPC, NDM, OXA-48-like, VIM) by the CarbaPCR, a phenotype termed CIM + Carba-. These isolates were mostly (81.9%) susceptible (EUCAST ≤ 2mg/L) to meropenem. The majority of CIM + Carba + isolates with major carbapenemase genes were gained from pre-emptive screening, while CIM + Carba- isolates were mainly taken for diagnostic purposes. Genomic analysis identified 18 genogroups, with E. kobei, E. roggenkampii, E. ludwigii, and K. aerogenes showing the CIM + Carba- phenotype, were mostly lacking porins and AmpC regulators, and correlated with chromosome-encoded AmpC-type β-lactamases like bla
ACT-28, bla
ACT-52,bla
MIR-3, bla
MIR-11 or ampC of which the majority (63%) yielded a positive CarbaNP-test. These CIM + Carba- isolates carried only few plasmids, and there was limited evidence of nosocomial spread. CIM + Carba- E. kobei carrying bla
ACT-28 overproduced ACT-28 protein in the CIM. Overall, the Enterobacter and K. aerogenes population in the Netherlands is genetically diverse, with most isolates carrying species-specific AmpC-type β-lactamases. Isolates with low MIC for meropenem that lack porins and major carbapenemases represent a low-risk for public health.
KW - AmpC
KW - Enterobacter
KW - <italic>K. aerogenes</italic>
KW - Surveillance
KW - Carbapenemase
KW - ACT
KW - MIR
KW - Carbapenem inactivation method
KW - Whole genome sequencing
KW - Resistance
KW - Carbapenemase activity
KW - RESISTANCE
KW - AMPC
KW - EXPRESSION
KW - ERTAPENEM
U2 - 10.1186/s12866-026-04741-1
DO - 10.1186/s12866-026-04741-1
M3 - Article
SN - 1471-2180
VL - 26
JO - BMC Microbiology
JF - BMC Microbiology
IS - 1
M1 - 192
ER -