The cystic fibrosis gut as a potential source of multidrug resistant pathogens

Steven L. Taylor, Lex E.X. Leong, Sarah K. Sims, Rebecca L. Keating, Lito E. Papanicolas, Alyson Richard, Fredrick M. Mobegi, Steve Wesselingh, Lucy D. Burr, Geraint B. Rogers

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: The emergence of multidrug resistant (MDR) pathogens represents a profound threat to global health. Individuals with CF have amongst the highest cumulative antibiotic exposure of any patient group, including to critically-important last-line agents. While there is little evidence that antibiotic resistance in airway pathogens results in worse clinical outcomes for CF patients, the potential emergence of MDR pathogens in non-respiratory systems, as a consequence of CF care, represents a potential health threat to the wider population, including family and carers. Methods: Stool from 19 adults with CF and 16 healthy adult controls was subjected to metagenomic sequencing, to assess faecal resistome, and culture-based analysis. Resistant isolates were identified phenotypically, and genetic determinants of resistance characterised by whole genome sequencing. Results: CF and control faecal resistomes differed significantly (P = 0.0003). The proportion of reads that mapped to mobile genetic elements was significantly higher in CF (P = 0.014) and the composition was significantly different (P = 0.0001). Notably, CF patients displayed higher carriage of plasmid-mediated aminoglycoside-modifying genes ant(6)-Ib, aac(6′)-Ip, and aph(3′)-IIIa (P < 0.01). Culture-based analysis supported higher aminoglycoside resistance, with a higher proportion of aminoglycoside-resistant, Gram-negative bacteria (P < 0.0001). Isolated extended spectrum beta lactamase (ESBL)-positive Escherichia coli from CF stool exhibited phenotypic resistance to tobramycin and gentamicin. Genomic analysis showed co-localisation of both aminoglycoside resistance and ESBL genes, consistent with MDR emergence through horizontal gene transfer. Conclusions: The carriage of potentially transmissible resistance within the adult CF gut microbiome is considerably greater than in healthy individuals and could contribute to the emergence and dissemination of MDR pathogens.

Original languageEnglish
Pages (from-to)413-420
Number of pages8
JournalJournal of Cystic Fibrosis
Volume20
Issue number3
Early online date26 Nov 2020
DOIs
Publication statusPublished - May 2021

Keywords

  • Anti-bacterial agents
  • Cystic fibrosis
  • Drug resistance
  • Microbiota
  • Resistome

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