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Nasal Resistome Development in Infants With Cystic Fibrosis in the First Year of Life.

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PubMed ID: 30863369

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Allemann A, Kraemer JG, Korten I, Ramsey K, Casaulta C, Wüthrich D, Ramette A, Endimiani A, Latzin P, Hilty M

Front Microbiol. 2019. doi: 10.3389/fmicb.2019.00212

COMMENT: It has been reported that patients with cystic fibrosis (CF) have complex lung microbiota with many genetic exchanges occurring by horizontal gene transfer, promoting the emergence of multidrug-resistant bacteria. This study analyzed the nasal resistome of infants with CF during the first year of life using a functional metagenomics approach that directly targets antibiotic non-susceptibly of the entire bacterial community, this method enables the identification of antimicrobial resistance genes (ARG) in bacterial genomes, including those that are currently unknown. The same classes of antibiotics (AB) used for the treatment of the infants were probed and nanopore MinION sequencing from Oxford Nanopore Technology was used. The main finding is that multiple antibiotic non-susceptibilities are present within the first months of life even if the infants have not yet been exposed to antibiotic treatment, which indicates that antibiotic treatment may not play a major role in the development of the resistome in the first year of life.

Objective

We aimed at setting up and establishing a functional metagenomic approach to describe the nasal resistome in infants with CF during the first year of life. Furthermore, we have aimed at more specifically investigating how the composition of the resistome is associated with antibiotic treatment and bacterial composition of the microbiota in patients with CF.

Main results

For all tested ABs, we identified efflux systems as the mechanism conferring resistance of which ABC and MSF transporters were the most common.

Overall, β-lactams-non-susceptibility was most frequently identified including 64 different predicted amino acid sequences recovered coding for β-lactamases

Analysis of the resistome association with AB Treatment and microbiota composition revealed no significant differences in the proportions of non-susceptible phenotypes between patients without an AB history, during AB treatment or after therapy

The possible taxonomic source (phylum) of each functionally selected resistance contig was predicted by using RAIphy, Proteobacteria and Firmicutes were the most prevalent predicted phyla.

The functional resistome analyses were compared with shotgun sequencing results for three samples and revealed resistance genes for antibiotics (e.g., macrolides and aminoglycosides) which were not detected by the functional resistome approach. The authors hypothesize that both methods have advantages and disadvantages and may be considered in the future for resistome analyses in CF.

Using functional metagenomics, we generally detected a large number of genes coding for β-lactam resistances of which some of them were well known and their detection was expected.

In our study, we used Nanopore MinION sequencing which has some distinct advantages. Nanopore reads are longer and typically capture the entire metagenomic inserts (…) which assures the definition and therefore enable a better characterization of the “mobilizable” resistome (..). However, the error rates are still higher as compared to other sequencing technologies (…) we investigated how mutations or error rate could potentially impact on the ARGs detection and found that the detection of ARGs was robust even with a high proportion of mutations.

Conclusion

We characterized the functional resistome of the nose in infants with CF during the first year of life. We revealed the presence of a large number or ARG, even if the infants were not yet exposed to antibiotic treatment. Understanding the resistome could potentially optimize clinical decision-making in patients with CF but this needs to be further investigated in future studies using clinically relevant samples.

Contributor

Diana López-Farfán