title: Cluster-dependent colistin hetero-resistance in Enterobacter cloacae complex.
abstract: Aims of this study were to: (i) evaluate whether the cluster membership could have an impact on hetero-resistance phenotype to colistin in the Enterobacter cloacae complex (ECC); and (ii) determine the genetic mechanism of colistin hetero-resistance in ECC.
  
  
  
  A collection of 124 clinical isolates belonging to 13 clusters were used to analyse the hetero-resistance phenotype (MICs were determined using the broth microdilution method, Etest and population analysis profiling). Different mutants (ΔphoP, ΔphoQ, ΔphoPQ, ΔpmrA, ΔpmrB, ΔpmrAB, ΔarnE, ΔarnF and ΔarnBCADTEF) were constructed and tested for their colistin hetero-resistance phenotype.
  
  
  
  Based on broth microdilution and Etest results, it was shown that the hetero-resistance to colistin depended on the cluster: strains from clusters I, II, IV, VII, IX, X, XI and XII were usually hetero-resistant, whereas those from clusters III, V, VI, VIII and XIII were categorized as susceptible. However, for some cluster V and VIII strains, a small proportion (<10-7) of cells appeared resistant when tested by population analysis profiling. From a mechanistic point of view, analysis of mutants revealed that the mechanism of hetero-resistance was mainly due to the expression of the arn operon and the phoP/phoQ two-component regulatory system.
  
  
  
  Because the colistin hetero-resistance appeared cluster-dependent in the ECC, it should be advocated to determine the cluster of the strain associated with the infection in parallel with the MIC of colistin. The resistance mechanism may not be similar to other Enterobacteriaceae since only the two-component regulatory system PhoP/PhoQ (and not PmrA/PmrB) seemed to play a role in resistance regulation.
authors: Université de Caen Normandie, EA4655 U2RM (équipe 'Antibio-résistance'), Caen, France.|CHU de Caen, Service de Microbiologie, Caen, France.|CNR de la Résistance aux Antibiotiques (laboratoire associé 'Entérocoques'), Caen, France.
authors: François
authors: F
authors: Guérin
authors: Université de Caen Normandie, EA4655 U2RM (équipe 'Antibio-résistance'), Caen, France.|CHU de Caen, Service de Microbiologie, Caen, France.
authors: Christophe
authors: C
authors: Isnard
authors: Université de Caen Normandie, EA4655 U2RM (équipe 'Antibio-résistance'), Caen, France.
authors: Clara
authors: C
authors: Sinel
authors: GH Cochin-Hôtel Dieu-Broca, AP-HP, Service de Microbiologie, Paris, France.
authors: Philippe
authors: P
authors: Morand
authors: Université de Caen Normandie, EA4655 U2RM (équipe 'Antibio-résistance'), Caen, France.
authors: Anne
authors: A
authors: Dhalluin
authors: Université de Caen Normandie, EA4655 U2RM (équipe 'Antibio-résistance'), Caen, France.|CHU de Caen, Service de Microbiologie, Caen, France.|CNR de la Résistance aux Antibiotiques (laboratoire associé 'Entérocoques'), Caen, France.
authors: Vincent
authors: V
authors: Cattoir
authors: Université de Caen Normandie, EA4655 U2RM (équipe 'Antibio-résistance'), Caen, France jean-christophe.giard@unicaen.fr.
authors: Jean-Christophe
authors: JC
authors: Giard
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D016972:Enterobacter cloacae / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D017353:Gene Deletion; D005798:Genes, Bacterial; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin