Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes

Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically important reservoir of resistance genes (resistome), yet prior studies indicate that the true diversity of gut-associated resistomes has been underestimated. To deeply characterize the pediatric gut-associat...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e78822-e78822
Main Authors: Moore, Aimée M, Patel, Sanket, Forsberg, Kevin J, Wang, Bin, Bentley, Gayle, Razia, Yasmin, Qin, Xuan, Tarr, Phillip I, Dantas, Gautam
Format: Article
Language:English
Subjects:
Adolescent
Aminoglycoside antibiotics
Anti-Bacterial Agents - pharmacology
Antibacterial agents
Antibiotic resistance
Antibiotics
Antimicrobial agents
Bacteria
Bacteroides - genetics
Beta lactamases
Biology
Child
Child, Preschool
Children
Chloramphenicol
Clostridium - genetics
Computer applications
Deoxyribonucleic acid
Dihydrofolate reductase
DNA
Drug resistance
Drug Resistance, Bacterial - genetics
E coli
Efflux
Enterobacter - genetics
Epidemiology
Escherichia coli
Fecal microflora
Feces
Feces - microbiology
Female
Folic acid
Genes
Genes, Bacterial
Genetic engineering
Genomes
Health risks
Humans
Hydrolase
Immunology
Infant
Infants
Intestinal microflora
Laboratories
Likelihood Functions
Male
Medicine
Methylase
Methyltransferases
Microbial drug resistance
Microbiota
Microbiota (Symbiotic organisms)
Microbiota - genetics
Molecular Sequence Annotation
Nucleotide sequence
Pathology
Pediatrics
Phylogeny
Proteins
Reductases
Regulators
RNA
rRNA (adenosine-2'-0'-)-methyltransferase
rRNA 16S
Sequence Analysis, DNA
Stools
Streptococcus infections
Synthesis
Teenagers
Transcription
Transcription (Genetics)
Transporter
Young Adult
β Lactamase
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Summary:Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically important reservoir of resistance genes (resistome), yet prior studies indicate that the true diversity of gut-associated resistomes has been underestimated. To deeply characterize the pediatric gut-associated resistome, we created metagenomic recombinant libraries in an Escherichia coli host using fecal DNA from 22 healthy infants and children (most without recent antibiotic exposure), and performed functional selections for resistance to 18 antibiotics from eight drug classes. Resistance-conferring DNA fragments were sequenced (Illumina HiSeq 2000), and reads assembled and annotated with the PARFuMS computational pipeline. Resistance to 14 of the 18 antibiotics was found in stools of infants and children. Recovered genes included chloramphenicol acetyltransferases, drug-resistant dihydrofolate reductases, rRNA methyltransferases, transcriptional regulators, multidrug efflux pumps, and every major class of beta-lactamase, aminoglycoside-modifying enzyme, and tetracycline resistance protein. Many resistance-conferring sequences were mobilizable; some had low identity to any known organism, emphasizing cryptic organisms as potentially important resistance reservoirs. We functionally confirmed three novel resistance genes, including a 16S rRNA methylase conferring aminoglycoside resistance, and two tetracycline-resistance proteins nearly identical to a bifidobacterial MFS transporter (B. longum s. longum JDM301). We provide the first report to our knowledge of resistance to folate-synthesis inhibitors conferred by a predicted Nudix hydrolase (part of the folate synthesis pathway). This functional metagenomic survey of gut-associated resistomes, the largest of its kind to date, demonstrates that fecal resistomes of healthy children are far more diverse than previously suspected, that clinically relevant resistance genes are present even without recent selective antibiotic pressure in the human host, and that cryptic gut microbes are an important resistance reservoir. The observed transferability of gut-associated resistance genes to a gram-negative (E. coli) host also suggests that the potential for gut-associated resistomes to threaten human health by mediating antibiotic resistance in pathogens warrants further investigation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0078822