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LMB-1 producing Citrobacter freundii from Argentina, a novel player in the field of MBLs.
Int J Antimicrob Agents 2019; :105857IJ

Abstract

Carbapenemase-producing Enterobacterales expressing OXA-48, KPC, NDM, VIM or IMP enzymes are increasingly reported worldwide. We have characterized LMB-1, a novel metallo-β-lactamase (MBL) of Ambler class B3 from Citrobacter freundii 164 (Cf164) clinical isolate from Buenos Aires, Argentina. Cf164 displayed reduced susceptibility to carbapenems but gave inconsistent results with carbapenemase confirmatory tests, indicating the presence of a weak carbapenemase. Analysis of whole-genome sequencing (WGS) of Cf164 using Resfinder revealed four β-lactamase genes coding for CTX-M-8, PER-2, TEM-1 and CMY-150, a novel chromosomally-encoded CMY variant. Kinetic parameters of purified CMY-150 did not reveal any carbapenemase activity. However, CMY-150 conferred higher minimum inhibitory concentrations (MICs) to E. coli for ceftazidime and aztreonam compared with CMY-2. The in-house-developed β-lactamase search software (ResMiner) in WGS data revealed a novel subclass B3 MBL named LMB-1. LMB-1 conferred resistance to penicillins and expanded-spectrum cephalosporins and reduced susceptibility to carbapenems in E. coli. The blaLMB-1 gene was located on a 176-kb IncA/C2 plasmid. LMB-1 shared 99% amino acid sequence identity with the MBL encoded in the chromosome of Rheinheimera pacifica, it's likely progenitor. Despite repeated attempts, LMB-1 could not be purified, thus only specific activities could indicate hydrolysis of carbapenems. Here we report on CMY-150, a novel CMY-2 variant that confers increased ceftazidime and aztreonam MICs to E. coli and the first description of LMB-1 in Argentina. This work underlines the need for several carbapenemase-producing Enterobacteriaceae (CPE) confirmatory tests, as this novel enzyme might have been missed using only one.

Authors+Show Affiliations

EA7361 "Structure, dynamic, function and expression of broad spectrum β-lactamases", Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France.Departamento de Bioquímica Clinica, Hospital de Clínicas José de San Martín, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.Departamento de Bioquímica Clinica, Hospital de Clínicas José de San Martín, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.EA7361 "Structure, dynamic, function and expression of broad spectrum β-lactamases", Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France; Department of Bacteriology-Hygiene, Bicêtre Hospital, APHP, Le Kremlin-Bicêtre, France; French National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France.EA7361 "Structure, dynamic, function and expression of broad spectrum β-lactamases", Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France; French National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France.Departamento de Bioquímica Clinica, Hospital de Clínicas José de San Martín, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.Université Paris-Saclay, CNRS, Institut de Chimie des Substances Naturelles, UPR 2301, Labex LERMIT, 91198, Gif-sur-Yvette, France.Departamento de Bioquímica Clinica, Hospital de Clínicas José de San Martín, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.EA7361 "Structure, dynamic, function and expression of broad spectrum β-lactamases", Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France; Department of Bacteriology-Hygiene, Bicêtre Hospital, APHP, Le Kremlin-Bicêtre, France; French National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France. Electronic address: thierry.naas@aphp.fr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31785341

Citation

Dabos, Laura, et al. "LMB-1 Producing Citrobacter Freundii From Argentina, a Novel Player in the Field of MBLs." International Journal of Antimicrobial Agents, 2019, p. 105857.
Dabos L, Rodriguez CH, Nastro M, et al. LMB-1 producing Citrobacter freundii from Argentina, a novel player in the field of MBLs. Int J Antimicrob Agents. 2019.
Dabos, L., Rodriguez, C. H., Nastro, M., Dortet, L., Bonnin, R. A., Famiglietti, A., ... Naas, T. (2019). LMB-1 producing Citrobacter freundii from Argentina, a novel player in the field of MBLs. International Journal of Antimicrobial Agents, p. 105857. doi:10.1016/j.ijantimicag.2019.11.014.
Dabos L, et al. LMB-1 Producing Citrobacter Freundii From Argentina, a Novel Player in the Field of MBLs. Int J Antimicrob Agents. 2019 Nov 27;105857. PubMed PMID: 31785341.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LMB-1 producing Citrobacter freundii from Argentina, a novel player in the field of MBLs. AU - Dabos,Laura, AU - Rodriguez,Carlos H, AU - Nastro,Marcela, AU - Dortet,Laurent, AU - Bonnin,Rémy A, AU - Famiglietti,Angela, AU - Iorga,Bogdan I, AU - Vay,Carlos, AU - Naas,Thierry, Y1 - 2019/11/27/ PY - 2019/07/26/received PY - 2019/11/18/revised PY - 2019/11/24/accepted PY - 2019/12/1/pubmed PY - 2019/12/1/medline PY - 2019/12/1/entrez KW - CPE KW - Carbapenemase KW - Class B3 MBL KW - Metallo-beta-lactamase SP - 105857 EP - 105857 JF - International journal of antimicrobial agents JO - Int. J. Antimicrob. Agents N2 - Carbapenemase-producing Enterobacterales expressing OXA-48, KPC, NDM, VIM or IMP enzymes are increasingly reported worldwide. We have characterized LMB-1, a novel metallo-β-lactamase (MBL) of Ambler class B3 from Citrobacter freundii 164 (Cf164) clinical isolate from Buenos Aires, Argentina. Cf164 displayed reduced susceptibility to carbapenems but gave inconsistent results with carbapenemase confirmatory tests, indicating the presence of a weak carbapenemase. Analysis of whole-genome sequencing (WGS) of Cf164 using Resfinder revealed four β-lactamase genes coding for CTX-M-8, PER-2, TEM-1 and CMY-150, a novel chromosomally-encoded CMY variant. Kinetic parameters of purified CMY-150 did not reveal any carbapenemase activity. However, CMY-150 conferred higher minimum inhibitory concentrations (MICs) to E. coli for ceftazidime and aztreonam compared with CMY-2. The in-house-developed β-lactamase search software (ResMiner) in WGS data revealed a novel subclass B3 MBL named LMB-1. LMB-1 conferred resistance to penicillins and expanded-spectrum cephalosporins and reduced susceptibility to carbapenems in E. coli. The blaLMB-1 gene was located on a 176-kb IncA/C2 plasmid. LMB-1 shared 99% amino acid sequence identity with the MBL encoded in the chromosome of Rheinheimera pacifica, it's likely progenitor. Despite repeated attempts, LMB-1 could not be purified, thus only specific activities could indicate hydrolysis of carbapenems. Here we report on CMY-150, a novel CMY-2 variant that confers increased ceftazidime and aztreonam MICs to E. coli and the first description of LMB-1 in Argentina. This work underlines the need for several carbapenemase-producing Enterobacteriaceae (CPE) confirmatory tests, as this novel enzyme might have been missed using only one. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/31785341/LMB-1_producing_Citrobacter_freundii_from_Argentina,_a_novel_player_in_the_field_of_MBLs L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(19)30328-0 DB - PRIME DP - Unbound Medicine ER -