| 1. |
- Berglund, Fanny, 1988, et al.
(author)
-
Identification and reconstruction of novel antibiotic resistance genes from metagenomes
- 2019
-
In: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 7:1
-
Journal article (peer-reviewed)abstract
- BackgroundEnvironmental and commensal bacteria maintain a diverse and largely unknown collection of antibiotic resistance genes (ARGs) that, over time, may be mobilized and transferred to pathogens. Metagenomics enables cultivation-independent characterization of bacterial communities but the resulting data is noisy and highly fragmented, severely hampering the identification of previously undescribed ARGs. We have therefore developed fARGene, a method for identification and reconstruction of ARGs directly from shotgun metagenomic data.ResultsfARGene uses optimized gene models and can therefore with high accuracy identify previously uncharacterized resistance genes, even if their sequence similarity to known ARGs is low. By performing the analysis directly on the metagenomic fragments, fARGene also circumvents the need for a high-quality assembly. To demonstrate the applicability of fARGene, we reconstructed -lactamases from five billion metagenomic reads, resulting in 221 ARGs, of which 58 were previously not reported. Based on 38 ARGs reconstructed by fARGene, experimental verification showed that 81% provided a resistance phenotype in Escherichia coli. Compared to other methods for detecting ARGs in metagenomic data, fARGene has superior sensitivity and the ability to reconstruct previously unknown genes directly from the sequence reads.ConclusionsWe conclude that fARGene provides an efficient and reliable way to explore the unknown resistome in bacterial communities. The method is applicable to any type of ARGs and is freely available via GitHub under the MIT license.
|
|
| 2. |
- Marathe, Nachiket, et al.
(author)
-
Sewage effluent from an Indian hospital harbors novel carbapenemases and integron-borne antibiotic resistance genes
- 2019
-
In: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 7:1
-
Journal article (peer-reviewed)abstract
- Background: Hospital wastewaters contain fecal material from a large number of individuals, of which many are undergoing antibiotic therapy. It is, thus, plausible that hospital wastewaters could provide opportunities to find novel carbapenemases and other resistance genes not yet described in clinical strains. Our aim was therefore to investigate the microbiota and antibiotic resistome of hospital effluent collected from the city of Mumbai, India, with a special focus on identifying novel carbapenemases. Results: Shotgun metagenomics revealed a total of 112 different mobile antibiotic resistance gene types, conferring resistance against almost all classes of antibiotics. Beta-lactamase genes, including encoding clinically important carbapenemases, such as NDM, VIM, IMP, KPC, and OXA-48, were abundant. NDM (0.9% relative abundance to 16S rRNA genes) was the most common carbapenemase gene, followed by OXA-58 (0.84% relative abundance to 16S rRNA genes). Among the investigated mobile genetic elements, class 1 integrons (11% relative abundance to 16S rRNA genes) were the most abundant. The genus Acinetobacter accounted for as many as 30% of the total 16S rRNA reads, with A. baumannii accounting for an estimated 2.5%. High throughput sequencing of amplified integron gene cassettes identified a novel functional variant of an IMP-type (proposed IMP-81) carbapenemase gene (eight aa substitutions) along with recently described novel resistance genes like sul4 and bla RSA1. Using a computational hidden Markov model, we detected 27 unique metallo-beta-lactamase (MBL) genes in the shotgun data, of which nine were novel subclass B1 genes, one novel subclass B2, and 10 novel subclass B3 genes. Six of the seven novel MBL genes were functional when expressed in Escherichia coli. Conclusion: By exploring hospital wastewater from India, our understanding of the diversity of carbapenemases has been extended. The study also demonstrates that the microbiota of hospital wastewater can serve as a reservoir of novel resistance genes, including previously uncharacterized carbapenemases with the potential to spread further.
|
|
| 3. |
- Söderström, Fanny, et al.
(author)
-
Reduced rate of retinopathy of prematurity after implementing lower oxygen saturation targets.
- 2019
-
In: Journal of Perinatology. - : Springer Science and Business Media LLC. - 0743-8346 .- 1476-5543. ; 39, s. 409-414
-
Journal article (peer-reviewed)abstract
- Objective: To evaluate an implementation of lower oxygen saturation targets with retinopathy of prematurity (ROP) as primary outcome, in infants at the lowest extreme of prematurity.Study design: Retrospective cohort including infants born at 22-25 weeks of gestation in 2005-2015 (n = 325), comparing high (87-93%) and low (85-90%) targets; infants transferred early were excluded from the main analysis to avoid bias.Results: Overall survival was 76% in high saturation era, and 69% in low saturation era (p = .17). Treatment-requiring ROP was less common in low saturation group (14% vs 28%, p < .05) with the most prominent difference in the most immature infants. Including deceased infants in the analysis, necrotizing enterocolitis was more frequent in low saturation era (21% vs 10%, p < .05).Conclusions: Implementing lower saturation targets resulted in a halved incidence of treatment-requiring ROP; the most immature infants seem to benefit the most. An association between lower oxygenation and necrotizing enterocolitis cannot be excluded.
|
|
