Detection of Bacteriophage Particles Containing Antibiotic Resistance Genes in the Sputum of Cystic Fibrosis Patients

Brown-Jaque, Maryury; Oyarzun, Lirain Rodriguez; Cornejo-Sánchez, Thais; Martín-Gómez, María Teresa; Gartner, Sílvia; Gracia, Javier de; Rovira, S.; Álvarez, Antonio; Jofre, Joan; González-López, Juan José; Muniesa, Maite

doi:10.3389/fmicb.2018.00856

Cited by 42 publications

(30 citation statements)

References 58 publications

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“…They are agents of ecosystem change because they prey on specific bacterial populations, mediate lateral gene transfer, alter host metabolism and redistribute bacterially derived compounds through cell lysis 2-4 . They spread antibiotic resistance 5 and disperse pathogenicity factors that cause disease in humans and animals 6,7 . Most knowledge about phages is based on laboratorystudied examples, the vast majority of which have genomes that are a few tens of kb in length.…”

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confidence: 99%

Clades of huge phages from across Earth’s ecosystems

Al-Shayeb

Sachdeva

Chen

et al. 2020

Nature

393

430

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Bacteriophages typically have small genomes 1 and depend on their bacterial hosts for replication 2 . Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems.Phages-viruses that infect bacteria-are considered distinct from cellular life owing to their inability to carry out most biological processes required for reproduction. They are agents of ecosystem change because they prey on specific bacterial populations, mediate lateral gene transfer, alter host metabolism and redistribute bacterially derived compounds through cell lysis 2-4 . They spread antibiotic resistance 5 and disperse pathogenicity factors that cause disease in humans and animals 6,7 . Most knowledge about phages is based on laboratorystudied examples, the vast majority of which have genomes that are a few tens of kb in length. Widely used isolation-based methods select against large phage particles, and they can be excluded from phage concentrates obtained by passage through 100-nm or 200-nm filters 1 . In 2017, only 93 isolated phages with genomes that were more than 200 kb in length were published 1 . Sequencing of whole-community DNA can uncover phage-derived fragments; however, large genomes can still escape detection owing to fragmentation 8 . A new clade of human-and animal-associated megaphages was recently described on the basis of genomes that were manually curated to completion from metagenomic datasets 9 . This finding prompted us to carry out a more-comprehensive analysis of microbial communities to evaluate the prevalence, diversity and ecosystem distribution of phages with large genomes. Previously, phages with genomes of more than 200 kb have been referred to as 'jumbophages' 1 or, in the case of phages with genomes of more than 500 kb, as megaphages 9 . As the set reconstructed here span both size ranges we refer to them simply as 'huge phage...

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mentioning

confidence: 99%

Clades of huge phages from across Earth’s ecosystems

Al-Shayeb

Sachdeva

Chen

et al. 2020

Nature

393

430

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“…While the potential challenges posed by the bacterial resistome in the lung21 22 and other body sites23 have been discussed, we are not aware of work directly comparable to the present study. Some previous respiratory studies addressing the resistome have concentrated on samples from cystic fibrosis patients24 25 and have attempted to reconcile detected resistance genes and phenotypic resistance in recognised pathogens as well as the intriguing potential of bacteriophages as vehicles of ARG dissemination 25 26. Most resistome studies have focused on faecal samples to assess the gut reservoir of ARGs and relationships to interchange with the local environment and geographic variations thereof 27–34.…”

Section: Discussionmentioning

confidence: 99%

Resistome analyses of sputum from COPD and healthy subjects reveals bacterial load-related prevalence of target genes

Ramsheh

Haldar

Bafadhel

et al. 2019

Thorax

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BackgroundAntibiotic resistance is a major global threat. We hypothesised that the chronic obstructive pulmonary disease (COPD) airway is a reservoir of antimicrobial resistance genes (ARGs) that associate with microbiome-specific COPD subgroups.ObjectiveTo determine the resistance gene profiles in respiratory samples from COPD patients and healthy volunteers.MethodsQuantitative PCR targeting 279 specific ARGs was used to profile the resistomes in sputum from subjects with COPD at stable, exacerbation and recovery visits (n=55; COPD-BEAT study), healthy controls with (n=7) or without (n=22) exposure to antibiotics in the preceding 12 months (EXCEED study) and in bronchial brush samples from COPD (n=8) and healthy controls (n=7) (EvA study).ResultsARG mean (SEM) prevalence was greater in stable COPD samples (35.2 (1.6)) than in healthy controls (27.6 (1.7); p=0.004) and correlated with total bacterial abundance (r2=0.23; p<0.001). Prevalence of ARG positive signals in individuals was not related to COPD symptoms, lung function or their changes at exacerbation. In the COPD subgroups designated High γProteobacteria and High Firmicutes, ARG prevalence was not different at stable state but significantly declined from stable through exacerbation to recovery in the former (p=0.011) without changes in total bacterial abundance. The ARG patterns were similar in COPD versus health, COPD microbiome-subgroups and between sputum and bronchoscopic samples independent of antibiotic exposure in the last 12 months.ConclusionsARGs are highly prevalent in sputum, broadly in proportion to bacterial abundance in both healthy and COPD subjects. Thus, COPD appears to be an ARG reservoir due to high levels of bacterial colonisation.

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“…The effector proteins are conserved among Salmonella strains, and it is presumably a result of horizontal gene transfer. Moreover, phages carrying antibacterial resistance genes were detected in the sputum from cystic fibrosis patients [60]. Conversely, another study analyzed the abundance of antibiotic resistance genes in more than one thousand phage genomes.…”

Section: Phages and Horizontal Gene Transfermentioning

confidence: 99%

Phages and Their Role in Gastrointestinal Disease: Focus on Inflammatory Bowel Disease

Marônek

Link

Ambro

et al. 2020

Cells

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Inflammatory bowel diseases (IBDs) are a group of chronic autoinflammatory diseases including Crohn’s disease and ulcerative colitis. Although the molecular mechanisms governing the pathogenesis of gastrointestinal inflammation are not completely clear, the main factors are presumed to be genetic predisposition, environmental exposure, and the intestinal microbiome. Hitherto, most of the studies focusing on the role of the microbiome studied the action and effect of bacteria. However, the intestinal microbiome comprises other members of the microbial community as well, namely, fungi, protozoa, and viruses. We believe that bacteriophages are among the main orchestrators of the effect of microbiota on the gut mucosa. Therefore, this review aims to summarize the knowledge of the role of intestinal phageome in IBD and to discuss the concept of phage therapy and its future applications.

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Detection of Bacteriophage Particles Containing Antibiotic Resistance Genes in the Sputum of Cystic Fibrosis Patients

Cited by 42 publications

References 58 publications

Clades of huge phages from across Earth’s ecosystems

Clades of huge phages from across Earth’s ecosystems

Resistome analyses of sputum from COPD and healthy subjects reveals bacterial load-related prevalence of target genes

Phages and Their Role in Gastrointestinal Disease: Focus on Inflammatory Bowel Disease

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