The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis. / Johnning, Anna; Karami, Nahid; Tång Hallbäck, Erika; Müller, Vilhelm; Nyberg, Lena; Buongermino Pereira, Mariana; Stewart, Callum; Ambjörnsson, Tobias; Westerlund, Fredrik; Adlerberth, Ingegerd; Kristiansson, Erik.

I: Microbial Genomics, Vol. 4, Nr. 11, 11.2018.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Johnning, A, Karami, N, Tång Hallbäck, E, Müller, V, Nyberg, L, Buongermino Pereira, M, Stewart, C, Ambjörnsson, T, Westerlund, F, Adlerberth, I & Kristiansson, E 2018, 'The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis', Microbial Genomics, vol. 4, nr. 11. https://doi.org/10.1099/mgen.0.000233

APA

Johnning, A., Karami, N., Tång Hallbäck, E., Müller, V., Nyberg, L., Buongermino Pereira, M., ... Kristiansson, E. (2018). The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis. Microbial Genomics, 4(11). https://doi.org/10.1099/mgen.0.000233

CBE

Johnning A, Karami N, Tång Hallbäck E, Müller V, Nyberg L, Buongermino Pereira M, Stewart C, Ambjörnsson T, Westerlund F, Adlerberth I, Kristiansson E. 2018. The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis. Microbial Genomics. 4(11). https://doi.org/10.1099/mgen.0.000233

MLA

Vancouver

Johnning A, Karami N, Tång Hallbäck E, Müller V, Nyberg L, Buongermino Pereira M et al. The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis. Microbial Genomics. 2018 nov;4(11). https://doi.org/10.1099/mgen.0.000233

Author

Johnning, Anna ; Karami, Nahid ; Tång Hallbäck, Erika ; Müller, Vilhelm ; Nyberg, Lena ; Buongermino Pereira, Mariana ; Stewart, Callum ; Ambjörnsson, Tobias ; Westerlund, Fredrik ; Adlerberth, Ingegerd ; Kristiansson, Erik. / The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis. I: Microbial Genomics. 2018 ; Vol. 4, Nr. 11.

RIS

TY - JOUR

T1 - The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis

AU - Johnning, Anna

AU - Karami, Nahid

AU - Tång Hallbäck, Erika

AU - Müller, Vilhelm

AU - Nyberg, Lena

AU - Buongermino Pereira, Mariana

AU - Stewart, Callum

AU - Ambjörnsson, Tobias

AU - Westerlund, Fredrik

AU - Adlerberth, Ingegerd

AU - Kristiansson, Erik

PY - 2018/11

Y1 - 2018/11

N2 - Carbapenem resistance is a rapidly growing threat to our ability to treat refractory bacterial infections. To understand how carbapenem resistance is mobilized and spread between pathogens, it is important to study the genetic context of the underlying resistance mechanisms. In this study, the resistomes of six clinical carbapenem-resistant isolates of five different species - Acinetobacter baumannii, Escherichia coli, two Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa - were characterized using whole genome sequencing. All Enterobacteriaceae isolates and the A. baumannii isolate had acquired a large number of antimicrobial resistance genes (7-18 different genes per isolate), including the following encoding carbapenemases: blaKPC-2, blaOXA-48, blaOXA-72, blaNDM-1, blaNDM-7 and blaVIM-1. In addition, a novel version of blaSHV was discovered. Four new resistance plasmids were identified and their fully assembled sequences were verified using optical DNA mapping. Most of the resistance genes were co-localized on these and other plasmids, suggesting a risk for co-selection. In contrast, five out of six carbapenemase genes were present on plasmids with no or few other resistance genes. The expected level of resistance - based on acquired resistance determinants - was concordant with measured levels in most cases. There were, however, several important discrepancies for four of the six isolates concerning multiple classes of antibiotics. In conclusion, our results further elucidate the diversity of carbapenemases, their mechanisms of horizontal transfer and possible patterns of co-selection. The study also emphasizes the difficulty of using whole genome sequencing for antimicrobial susceptibility testing of pathogens with complex genotypes.

AB - Carbapenem resistance is a rapidly growing threat to our ability to treat refractory bacterial infections. To understand how carbapenem resistance is mobilized and spread between pathogens, it is important to study the genetic context of the underlying resistance mechanisms. In this study, the resistomes of six clinical carbapenem-resistant isolates of five different species - Acinetobacter baumannii, Escherichia coli, two Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa - were characterized using whole genome sequencing. All Enterobacteriaceae isolates and the A. baumannii isolate had acquired a large number of antimicrobial resistance genes (7-18 different genes per isolate), including the following encoding carbapenemases: blaKPC-2, blaOXA-48, blaOXA-72, blaNDM-1, blaNDM-7 and blaVIM-1. In addition, a novel version of blaSHV was discovered. Four new resistance plasmids were identified and their fully assembled sequences were verified using optical DNA mapping. Most of the resistance genes were co-localized on these and other plasmids, suggesting a risk for co-selection. In contrast, five out of six carbapenemase genes were present on plasmids with no or few other resistance genes. The expected level of resistance - based on acquired resistance determinants - was concordant with measured levels in most cases. There were, however, several important discrepancies for four of the six isolates concerning multiple classes of antibiotics. In conclusion, our results further elucidate the diversity of carbapenemases, their mechanisms of horizontal transfer and possible patterns of co-selection. The study also emphasizes the difficulty of using whole genome sequencing for antimicrobial susceptibility testing of pathogens with complex genotypes.

KW - carbapenem resistance

KW - genotype–phenotype association

KW - human pathogens

KW - whole-genome sequencing

U2 - 10.1099/mgen.0.000233

DO - 10.1099/mgen.0.000233

M3 - Article

VL - 4

JO - Microbial Genomics

JF - Microbial Genomics

SN - 2057-5858

IS - 11

ER -