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

• 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 colt, 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: bla(KPC-2), bla(OXA-48), bla(OXA-72), bla(NDM-1), bla(NDm-7) and bla(VIM-1). In addition, a novel version of bla(SHv) 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 colocalized on these and other plasmids, suggesting a risk for coselection. 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

NATURVETENSKAP  -- Biologi -- Mikrobiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Microbiology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Biofysik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biophysics (hsv//eng)

NATURVETENSKAP  -- Fysik -- Annan fysik (hsv//swe)

NATURAL SCIENCES  -- Physical Sciences -- Other Physics Topics (hsv//eng)

Nyckelord

whole-genome sequencing

carbapenem resistance

genotype-phenotype association

human

metallo-beta-lactamase

complete nucleotide-sequence

pseudomonas-aeruginosa

antibiotic-resistance

escherichia-coli

antimicrobial resistance

klebsiella-pneumoniae

topoisomerase-iv

quinolone-resistance

bacterial-resistance

carbapenem resistance

genotype–phenotype association

human pathogens

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)