Phylogenetic barriers to horizontal transfer of antimicrobial peptide resistance genes in the human gut microbiota

Kintses, Bálint and Méhi, Orsolya Katinka and Ari, Eszter and Számel, Mónika and Györkei, Ádám and Jangir, Pramod Kumar and Nagy, István and Pál, Ferenc and Fekete, Gergely and Tengölics, Roland and Nyerges, Ákos and Likó, István and Bálint, Anita and Molnár, Tamás and Vásárhelyi, Bálint Márk and Bustamante, Misshelle and Papp, Balázs and Pál, Csaba (2019) Phylogenetic barriers to horizontal transfer of antimicrobial peptide resistance genes in the human gut microbiota. NATURE MICROBIOLOGY. ISSN 2058-5276

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Abstract

The human gut microbiota has adapted to the presence of antimicrobial peptides (AMPs), which are ancient components of immune defence. Despite its medical importance, it has remained unclear whether AMP resistance genes in the gut microbiome are available for genetic exchange between bacterial species. Here, we show that AMP resistance and antibiotic resistance genes differ in their mobilization patterns and functional compatibilities with new bacterial hosts. First, whereas AMP resistance genes are widespread in the gut microbiome, their rate of horizontal transfer is lower than that of antibiotic resistance genes. Second, gut microbiota culturing and functional metagenomics have revealed that AMP resistance genes originating from phylogenetically distant bacteria have only a limited potential to confer resistance in Escherichia coli, an intrinsically susceptible species. Taken together, functional compatibility with the new bacterial host emerges as a key factor limiting the genetic exchange of AMP resistance genes. Finally, our results suggest that AMPs induce highly specific changes in the composition of the human microbiota, with implications for disease risks.

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