open access publication

Article, 2024

Co-localization of antibiotic resistance genes is widespread in the infant gut microbiome and associates with an immature gut microbial composition

Microbiome, ISSN 2049-2618, Volume 12, 1, Page 87, 10.1186/s40168-024-01800-5

Contributors

Li, Xuanji 0000-0001-8835-488X (Corresponding author) [1] Brejnrod, Asker Daniel 0000-0002-1327-2051 [2] Trivedi, Urvish 0000-0003-1541-6212 [1] Russel, Jakob 0000-0002-0565-3161 [1] Thorsen, Jonathan 0000-0003-0200-0461 [1] Shah, Shiraz Ali 0000-0002-4665-577X [1] Vestergaard, Gisle Alberg 0000-0003-2541-4974 [2] Rasmussen, Morten Arendt 0000-0001-7431-5206 [1] Nesme, Joseph 0000-0003-1929-5040 [1] Bisgaard, Hans 0000-0003-4131-7592 [1] Stokholm, Jakob 0000-0003-4989-9769 [1] Sørensen, Søren Johannes 0000-0001-6227-9906 [1]

Affiliations

  1. [1] University of Copenhagen
  2. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  3. [2] Technical University of Denmark
  4. [NORA names: DTU Technical University of Denmark; University; Denmark; Europe, EU; Nordic; OECD]

Abstract

BackgroundIn environmental bacteria, the selective advantage of antibiotic resistance genes (ARGs) can be increased through co-localization with genes such as other ARGs, biocide resistance genes, metal resistance genes, and virulence genes (VGs). The gut microbiome of infants has been shown to contain numerous ARGs, however, co-localization related to ARGs is unknown during early life despite frequent exposures to biocides and metals from an early age.ResultsWe conducted a comprehensive analysis of genetic co-localization of resistance genes in a cohort of 662 Danish children and examined the association between such co-localization and environmental factors as well as gut microbial maturation. Our study showed that co-localization of ARGs with other resistance and virulence genes is common in the early gut microbiome and is associated with gut bacteria that are indicative of low maturity. Statistical models showed that co-localization occurred mainly in the phylum Proteobacteria independent of high ARG content and contig length. We evaluated the stochasticity of co-localization occurrence using enrichment scores. The most common forms of co-localization involved tetracycline and fluoroquinolone resistance genes, and, on plasmids, co-localization predominantly occurred in the form of class 1 integrons. Antibiotic use caused a short-term increase in mobile ARGs, while non-mobile ARGs showed no significant change. Finally, we found that a high abundance of VGs was associated with low gut microbial maturity and that VGs showed even higher potential for mobility than ARGs.ConclusionsWe found that the phenomenon of co-localization between ARGs and other resistance and VGs was prevalent in the gut at the beginning of life. It reveals the diversity that sustains antibiotic resistance and therefore indirectly emphasizes the need to apply caution in the use of antimicrobial agents in clinical practice, animal husbandry, and daily life to mitigate the escalation of resistance.CR8ihftTez1HgYaufYhgHyVideo Abstract

Keywords

Arg content, ConclusionsWe, Danish children, No significant changes, Proteobacteria, ResultsWe, abundance, abundance of virulence genes, age, agents, animal husbandry, animals, antibiotic resistance, antibiotic resistance genes, antibiotic use, antimicrobial agents, association, associations with gut bacteria, bacteria, biocide resistance genes, biocides, changes, children, class, class 1 integrons, clinical practice, co-localization, cohort, composition, comprehensive analysis, content, contig length, contigs, daily life, diversity, early age, early gut microbiome, early life, environmental bacteria, environmental factors, escalation, escalation of resistance, exposure, factors, fluoroquinolone resistance genes, frequent exposure, genes, gut, gut bacteria, gut microbial composition, gut microbiome, gut microbiome of infants, husbandry, increase, infant gut microbiome, infants, length, life, low maturity, maturation, metal, metal resistance genes, microbial composition, microbial maturation, microbiome, microbiome of infants, mobile antibiotic resistance genes, mobility, model, occurrence, phenomenon, phenomenon of co-localization, phylum, phylum Proteobacteria, plasmid, potential, practice, resistance, resistance genes, scores, short-term increase, significant changes, statistical model, stochasticity, study, tetracycline, use, virulence, virulence genes

Funders

  • Novo Nordisk Foundation

Data Provider: Digital Science