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

By Bálint Kintses, Orsolya Méhi, Eszter Ari, Mónika Számel, Ádám Györkei, Pramod K Jangir, István Nagy, Ferenc Pál, Gergö Fekete, Roland Tengölics, Akos Nyerges, István Likó, Balázs Bálint, Bálint Márk Vásárhelyi, Misshelle Bustamante, Balázs Papp, Csaba Pál

Posted 07 Aug 2018
bioRxiv DOI: 10.1101/385831 (published DOI: 10.1038/s41564-018-0313-5)

The human gut microbiota has adapted to the presence of antimicrobial peptides (AMPs) that are ancient components of immune defence. Despite important medical relevance, 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- 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 revealed that AMP resistance genes originating from phylogenetically distant bacteria only have a limited potential to confer resistance in Escherichia coli, an intrinsically susceptible species. Third, the phenotypic impact of acquired AMP resistance genes heavily depends on the genetic background of the recipient bacteria. 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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