A Clostridium Difficile Lineage Endemic to Costa Rican Hospitals Is Multidrug Resistant by Acquisition of Chromosomal Mutations and Novel Mobile Genetic Elements

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2017 Feb 1

PMID 28137804

Citations 10

Authors

Gabriel Ramirez-Vargas

Carlos Quesada-Gomez

Luis Acuna-Amador

Diana Lopez-Urena

Tatiana Murillo

Maria Del Mar Gamboa-Coronado

Esteban Chaves-Olarte

Nicholas Thomson

Evelyn Rodriguez-Cavallini

Cesar Rodriguez

Affiliations

Soon will be listed here.

Abstract

The antimicrobial resistance (AMR) rates and levels recorded for are on the rise. This study reports the nature, levels, diversity, and genomic context of the antimicrobial resistance of human isolates of the NAP/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 NAP isolates to 10 antibiotics from seven classes using Etests or macrodilution tests and examined 31 NAP whole-genome sequences to identify single nucleotide polymorphisms (SNPs) and genes that could explain the resistance phenotypes observed. The NAP isolates were multidrug resistant (MDR) and commonly exhibited very high resistance levels. By sequencing their genomes, we showed that they possessed resistance-associated SNPs in and and 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 NAP lineage 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 more MDR strains.

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References

Goh S, Hussain H, Chang B, Emmett W, Riley T, Mullany P . Phage ϕC2 mediates transduction of Tn6215, encoding erythromycin resistance, between Clostridium difficile strains. mBio. 2013; 4(6):e00840-13. PMC: 3870246. DOI: 10.1128/mBio.00840-13. View

Pelaez T, Alcala L, Alonso R, Martin-Lopez A, Garcia-Arias V, Marin M . In vitro activity of ramoplanin against Clostridium difficile, including strains with reduced susceptibility to vancomycin or with resistance to metronidazole. Antimicrob Agents Chemother. 2005; 49(3):1157-9. PMC: 549223. DOI: 10.1128/AAC.49.3.1157-1159.2005. View

Mullany P, Allan E, Roberts A . Mobile genetic elements in Clostridium difficile and their role in genome function. Res Microbiol. 2015; 166(4):361-7. PMC: 4430133. DOI: 10.1016/j.resmic.2014.12.005. View

Bi D, Xu Z, Harrison E, Tai C, Wei Y, He X . ICEberg: a web-based resource for integrative and conjugative elements found in Bacteria. Nucleic Acids Res. 2011; 40(Database issue):D621-6. PMC: 3244999. DOI: 10.1093/nar/gkr846. View

Seemann T . Prokka: rapid prokaryotic genome annotation. Bioinformatics. 2014; 30(14):2068-9. DOI: 10.1093/bioinformatics/btu153. View

Li H . A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics. 2011; 27(21):2987-93. PMC: 3198575. DOI: 10.1093/bioinformatics/btr509. View

Fry P, Thakur S, Abley M, Gebreyes W . Antimicrobial resistance, toxinotype, and genotypic profiling of Clostridium difficile isolates of swine origin. J Clin Microbiol. 2012; 50(7):2366-72. PMC: 3405606. DOI: 10.1128/JCM.06581-11. View

Miller B, Chen L, Sexton D, Anderson D . Comparison of the burdens of hospital-onset, healthcare facility-associated Clostridium difficile Infection and of healthcare-associated infection due to methicillin-resistant Staphylococcus aureus in community hospitals. Infect Control Hosp Epidemiol. 2011; 32(4):387-90. DOI: 10.1086/659156. View

Fouhy F, Ogilvie L, Jones B, Ross R, Ryan A, Dempsey E . Identification of aminoglycoside and β-lactam resistance genes from within an infant gut functional metagenomic library. PLoS One. 2014; 9(9):e108016. PMC: 4172600. DOI: 10.1371/journal.pone.0108016. View

10.

Sullivan M, Petty N, Beatson S . Easyfig: a genome comparison visualizer. Bioinformatics. 2011; 27(7):1009-10. PMC: 3065679. DOI: 10.1093/bioinformatics/btr039. View

11.

Zerbino D, Birney E . Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Res. 2008; 18(5):821-9. PMC: 2336801. DOI: 10.1101/gr.074492.107. View

12.

Farrow K, Lyras D, Rood J . The macrolide-lincosamide-streptogramin B resistance determinant from Clostridium difficile 630 contains two erm(B) genes. Antimicrob Agents Chemother. 2000; 44(2):411-3. PMC: 89693. DOI: 10.1128/AAC.44.2.411-413.2000. View

13.

Shah D, Dang M, Hasbun R, Koo H, Jiang Z, DuPont H . Clostridium difficile infection: update on emerging antibiotic treatment options and antibiotic resistance. Expert Rev Anti Infect Ther. 2010; 8(5):555-64. PMC: 3138198. DOI: 10.1586/eri.10.28. View

14.

Sebaihia M, Wren B, Mullany P, Fairweather N, Minton N, Stabler R . The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome. Nat Genet. 2006; 38(7):779-86. DOI: 10.1038/ng1830. View

15.

Spigaglia P, Barbanti F, Mastrantonio P . Detection of a genetic linkage between genes coding for resistance to tetracycline and erythromycin in Clostridium difficile. Microb Drug Resist. 2007; 13(2):90-5. DOI: 10.1089/mdr.2007.723. View

16.

Shen J, Wang Y, Schwarz S . Presence and dissemination of the multiresistance gene cfr in Gram-positive and Gram-negative bacteria. J Antimicrob Chemother. 2013; 68(8):1697-706. DOI: 10.1093/jac/dkt092. View

17.

Hernandez D, Tewhey R, Veyrieras J, Farinelli L, Osteras M, Francois P . De novo finished 2.8 Mbp Staphylococcus aureus genome assembly from 100 bp short and long range paired-end reads. Bioinformatics. 2013; 30(1):40-9. PMC: 6280916. DOI: 10.1093/bioinformatics/btt590. View

18.

Ammam F, Marvaud J, Lambert T . Distribution of the vanG-like gene cluster in Clostridium difficile clinical isolates. Can J Microbiol. 2012; 58(4):547-51. DOI: 10.1139/w2012-002. View

19.

Quesada-Gomez C, Lopez-Urena D, Acuna-Amador L, Villalobos-Zuniga M, Du T, Freire R . Emergence of an outbreak-associated Clostridium difficile variant with increased virulence. J Clin Microbiol. 2015; 53(4):1216-26. PMC: 4365207. DOI: 10.1128/JCM.03058-14. View

20.

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N . The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009; 25(16):2078-9. PMC: 2723002. DOI: 10.1093/bioinformatics/btp352. View