title: Deciphering the Resistome of the Widespread Pseudomonas aeruginosa Sequence Type 175 International High-Risk Clone through Whole-Genome Sequencing.
abstract: Whole-genome sequencing (WGS) was used for the characterization of the frequently extensively drug resistant (XDR) Pseudomonas aeruginosa sequence type 175 (ST175) high-risk clone. A total of 18 ST175 isolates recovered from 8 different Spanish hospitals were analyzed; 4 isolates from 4 different French hospitals were included for comparison. The typical resistance profile of ST175 included penicillins, cephalosporins, monobactams, carbapenems, aminoglycosides, and fluoroquinolones. In the phylogenetic analysis, the four French isolates clustered together with two isolates from one of the Spanish regions. Sequence variation was analyzed for 146 chromosomal genes related to antimicrobial resistance, and horizontally acquired genes were explored using online databases. The resistome of ST175 was determined mainly by mutational events; resistance traits common to all or nearly all of the strains included specific ampR mutations leading to ampC overexpression, specific mutations in oprD conferring carbapenem resistance, or a mexZ mutation leading to MexXY overexpression. All isolates additionally harbored an aadB gene conferring gentamicin and tobramycin resistance. Several other resistance traits were specific to certain geographic areas, such as a streptomycin resistance gene, aadA13, detected in all four isolates from France and in the two isolates from the Cantabria region and a glpT mutation conferring fosfomycin resistance, detected in all but these six isolates. Finally, several unique resistance mutations were detected in single isolates; particularly interesting were those in genes encoding penicillin-binding proteins (PBP1A, PBP3, and PBP4). Thus, these results provide information valuable for understanding the genetic basis of resistance and the dynamics of the dissemination and evolution of high-risk clones.
authors.affiliation: Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain.
authors.forename: Gabriel
authors.identifier: 0000-0002-6452-9945
authors.initials: G
authors.lastname: Cabot
authors.affiliation: Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: López-Causapé
authors.affiliation: Servicio de Microbiología, Hospital Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla, Santander, Spain.
authors.forename: Alain A
authors.initials: AA
authors.lastname: Ocampo-Sosa
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark.
authors.forename: Lea M
authors.initials: LM
authors.lastname: Sommer
authors.affiliation: Servicio de Microbiología Hospital Bellvitge, Barcelona, Spain, and CIBERES, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Domínguez
authors.affiliation: Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Zamorano
authors.affiliation: Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Juan
authors.affiliation: Servicio de Microbiología Hospital Bellvitge, Barcelona, Spain, and CIBERES, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Fe
authors.initials: F
authors.lastname: Tubau
authors.affiliation: Servicio de Microbiología, Hospital Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla, Santander, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez
authors.affiliation: Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain.
authors.forename: Bartolomé
authors.initials: B
authors.lastname: Moyà
authors.affiliation: Servicio de Medicina Interna, Hospital Virgen de los Lirios, Alcoy, Spain.
authors.forename: Carmen
authors.identifier: 0000-0002-6673-2883
authors.initials: C
authors.lastname: Peña
authors.affiliation: Servicio de Microbiología, Hospital Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla, Santander, Spain.|Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Martínez
authors.affiliation: French National Reference Center for Antibiotic Resistance, University Hospital of Besançon, Besançon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Plesiat
authors.affiliation: Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain antonio.oliver@ssib.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliver
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015780:Carbapenems / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D002999:Clone Cells; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology; D005602:France / Q000453:epidemiology; D015870:Gene Expression; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing; D006761:Hospitals; D006801:Humans; D008826:Microbial Sensitivity Tests; D008997:Monobactams / Q000494:pharmacology; D009154:Mutation; D010406:Penicillins / Q000494:pharmacology; D010802:Phylogeny; D018272:Porins / Q000235:genetics / Q000378:metabolism; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D013030:Spain / Q000453:epidemiology; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D002511:Cephalosporins; D024841:Fluoroquinolones; C402791:MexXY protein, Pseudomonas aeruginosa; C402792:MexZ protein, Pseudomonas aeruginosa; D008997:Monobactams; D010406:Penicillins; D018272:Porins; C071526:AmpR protein, Bacteria; C077157:OprD protein, Pseudomonas aeruginosa; C048795:AmpC beta-lactamases; D001618:beta-Lactamases