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Prophages as a source of antimicrobial resistance genes in the human microbiome
Laura K Inglis1, Susanna R Grigson1, Michael J Roach1,2
1Flinders Accelerator for Microbiome Exploration, College of Science and Engineering, Flinders University, Bedford Park, SA, 5042, Australia.
Abstract:
Prophages-viruses that integrate into bacterial genomes-are ubiquitous in the microbial realm. Prophages contribute significantly to horizontal gene transfer, including the potential spread of antimicrobial resistance (AMR) genes, because they can collect host genes. Understanding their role in the human microbiome is essential for fully understanding AMR dynamics and possible clinical implications. We analysed almost 15,000 bacterial genomes for prophages and AMR genes. The bacteria were isolated from diverse human body sites and geographical regions, and their genomes were retrieved from GenBank. AMR genes were detected in 6.6% of bacterial genomes, with a higher prevalence in people with symptomatic diseases. We found a wide variety of AMR genes combating multiple drug classes. We discovered AMR genes previously associated with plasmids, such as blaOXA-23 in Acinetobacter baumannii prophages or genes found in prophages in species they had not been previously described in, such as mefA-msrD in Gardnerella prophages, suggesting prophage-mediated gene transfer of AMR genes. Prophages encoding AMR genes were found at varying frequencies across body sites and geographical regions, with Asia showing the highest diversity of AMR genes.
Insights
Prophages, viruses in bacteria, can spread antimicrobial resistance (AMR) genes. Our analysis of human bacterial genomes revealed AMR genes within prophages, highlighting their role in resistance transfer.
Area of Science:
- Microbiology
- Genomics
- Virology
Background:
- Prophages are integrated viral elements within bacterial genomes, prevalent across microbial ecosystems.
- These elements play a significant role in horizontal gene transfer, potentially mediating the spread of antimicrobial resistance (AMR) genes.
- Understanding prophage involvement in AMR is crucial for human microbiome research and clinical applications.
Purpose of the Study:
- To investigate the prevalence and diversity of prophages carrying AMR genes in the human microbiome.
- To identify specific AMR genes and prophage-host associations within human-associated bacteria.
- To assess the geographical and body-site distribution of AMR-encoding prophages.
Main Methods:
- Analysis of nearly 15,000 bacterial genomes from diverse human body sites and geographical locations, sourced from GenBank.
- Bioinformatic identification and characterization of prophage sequences within bacterial genomes.
- Detection and classification of antimicrobial resistance genes harbored by prophages and their hosts.
Main Results:
- Antimicrobial resistance genes were identified in 6.6% of analyzed bacterial genomes, with higher frequency in symptomatic individuals.
- A broad spectrum of AMR genes, including those previously linked to plasmids, were found within prophages.
- Novel prophage-AMR gene associations were discovered, such as 'blaOXA-23' in Acinetobacter baumannii and 'mefA-msrD' in Gardnerella species, suggesting prophage-mediated transfer.
- Prophages carrying AMR genes exhibited varied frequencies across body sites, with the highest diversity observed in Asia.
Conclusions:
- Prophages are significant vectors for the dissemination of antimicrobial resistance genes within the human microbiome.
- The presence of AMR genes in prophages underscores their potential clinical implications for treatment strategies.
- Further research into prophage-host-AMR interactions is warranted to combat the growing threat of antimicrobial resistance.
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