HAM-ART: An optimised culture-free Hi-C metagenomics pipeline for tracking antimicrobial resistance genes in complex microbial communities

Kalmar, L; Gupta, S; Kean, IRL; Ba, X; Hadjirin, N; Lay, EM; de Vries, SPW; Bateman, M; Bartlet, H; Hernandez-Garcia, J; Tucker, AW; Restif, O; Stevens, MP; Wood, JLN; Maskell, DJ; Grant, AJ; Holmes, MA

Journal article

HAM-ART: An optimised culture-free Hi-C metagenomics pipeline for tracking antimicrobial resistance genes in complex microbial communities

Abstract:: The human gut harbours a complex microbial ecosystem, termed the gut microbiome, that includes hundreds of bacterial species. Whilst most bacteria in the human gut have a commensal or mutualistic relationship with their host, the gut microbiome can also act as a reservoir for antimicrobial resistance genes (ARGs). Collectively, these ARGs are known as the gut resistome. Recent decades have seen a rise in multidrug-resistant infections caused by opportunistic pathogens originating from the gut microbiome. There is thus a need to characterise which bacterial species carry and transfer ARGs in the gut. Here, I explored the human gut resistome using chromosome conformation capture (3C) techniques to link ARGs to their bacterial hosts. Metagenomic 3C was implemented on a human faecal sample, and an analysis of my own and published datasets from 3C-based gut microbiome studies revealed that short reads mapping to repetitive elements causes problematic noise during analysis of 3C data. A bioinformatic workflow named H-LARGe (Host-Linkage to Antimicrobial Resistance Genes) was developed to reduce the impact of this noise and successfully link ARGs to their hosts. Next, a derivative of 3C, called Hi-C, was performed on four human faecal samples. Analysis of the data using an updated version of the H-LARGe workflow indicated that ARGs, including clinically important multiresistance genes, were widespread in commensal species from the gut microbiota. Following Hi-C analysis, the hosts of several ARGs were cultured and whole-genome sequenced using both short- and long-read technologies. These data provided genomic context for the ARGs and offered insights into the limitations of using Hi-C to link ARGs to their host in complex metagenomic samples. This highlighted the complementarity of Hi-C and culture-based approaches to fully characterise the gut resistome

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Kalmar, L., Gupta, S., Kean, I. R. L., Ba, X., Hadjirin, N., Lay, E. M., de Vries, S. P. W., Bateman, M., Bartlet, H., Hernandez-Garcia, J., Tucker, A. W., Restif, O., Stevens, M. P., Wood, J. L. N., Maskell, D. J., Grant, A. J., & Holmes, M. A. (2022). HAM-ART: An optimised culture-free Hi-C metagenomics pipeline for tracking antimicrobial resistance genes in complex microbial communities. PLoS Genetics, 18(3), e1009776–e1009776.

MLA Style

Kalmar, L, et al. “HAM-ART: An Optimised Culture-Free Hi-C Metagenomics Pipeline for Tracking Antimicrobial Resistance Genes in Complex Microbial Communities.” PLoS Genetics, vol. 18, no. 3, 2022, pp. e1009776–e1009776.

Chicago Style

Kalmar, L, S Gupta, IRL Kean, et al. 2022. “HAM-ART: An Optimised Culture-Free Hi-C Metagenomics Pipeline for Tracking Antimicrobial Resistance Genes in Complex Microbial Communities.” PLoS Genetics 18 (3): e1009776–e1009776.
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