title: A Clostridium difficile Lineage Endemic to Costa Rican Hospitals Is Multidrug Resistant by Acquisition of Chromosomal Mutations and Novel Mobile Genetic Elements.
abstract: The antimicrobial resistance (AMR) rates and levels recorded forClostridium difficileare on the rise. This study reports the nature, levels, diversity, and genomic context of the antimicrobial resistance of humanC. difficileisolates of the NAPCR1/RT012/ST54 genotype, which caused an outbreak in 2009 and is endemic in Costa Rican hospitals. To this end, we determined the susceptibilities of 38 NAPCR1isolates to 10 antibiotics from seven classes using Etests or macrodilution tests and examined 31 NAPCR1whole-genome sequences to identify single nucleotide polymorphisms (SNPs) and genes that could explain the resistance phenotypes observed. The NAPCR1isolates were multidrug resistant (MDR) and commonly exhibited very high resistance levels. By sequencing their genomes, we showed that they possessed resistance-associated SNPs ingyrAandrpoBand carried eight to nine acquired antimicrobial resistance (AMR) genes. Most of these genes were located on known or novel mobile genetic elements shared by isolates recovered at different hospitals and at different time points. Metronidazole and vancomycin remain the first-line treatment options for these isolates. Overall, the NAPCR1lineage showed an enhanced ability to acquire AMR genes through lateral gene transfer. On the basis of this finding, we recommend further vigilance and the adoption of improved control measures to limit the dissemination of this lineage and the emergence of moreC. difficileMDR strains.
authors.affiliation: Laboratorio de Investigación en Bacteriología Anaerobia, Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología,Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ramírez-Vargas
authors.affiliation: Laboratorio de Investigación en Bacteriología Anaerobia, Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología,Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Carlos
authors.initials: C
authors.lastname: Quesada-Gómez
authors.affiliation: Laboratorio de Investigación en Bacteriología Anaerobia, Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología,Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Luis
authors.initials: L
authors.lastname: Acuña-Amador
authors.affiliation: Laboratorio de Investigación en Bacteriología Anaerobia, Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología,Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Diana
authors.initials: D
authors.lastname: López-Ureña
authors.affiliation: Laboratorio de Investigación en Bacteriología Anaerobia, Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología,Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Murillo
authors.affiliation: Laboratorio de Investigación en Bacteriología Anaerobia, Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología,Universidad de Costa Rica, San José, Costa Rica.
authors.forename: María
authors.initials: M
authors.lastname: Del Mar Gamboa-Coronado
authors.affiliation: Laboratorio de Investigación en Bacteriología Anaerobia, Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología,Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Esteban
authors.initials: E
authors.lastname: Chaves-Olarte
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.|London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Thomson
authors.affiliation: Laboratorio de Investigación en Bacteriología Anaerobia, Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología,Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Rodríguez-Cavallini
authors.affiliation: Laboratorio de Investigación en Bacteriología Anaerobia, Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología,Universidad de Costa Rica, San José, Costa Rica cesar.rodriguezsanchez@ucr.ac.cr.
authors.forename: César
authors.identifier: 0000-0001-5599-0652
authors.initials: C
authors.lastname: Rodríguez
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016360:Clostridioides difficile / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D003015:Clostridium Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D003364:Costa Rica / Q000453:epidemiology; D027081:DNA Gyrase / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D019353:Endemic Diseases; D015870:Gene Expression; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006761:Hospitals; D006801:Humans; D020071:Interspersed Repetitive Sequences; D008795:Metronidazole / Q000494:pharmacology; D009154:Mutation; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D008795:Metronidazole; D014640:Vancomycin; D012321:DNA-Directed RNA Polymerases; D027081:DNA Gyrase
keywords: Clostridium difficile; NAPCR1; comparative genomics; multidrug resistance