title: Exploring divergent antibiotic resistance genes in ancient metagenomes and discovery of a novel beta-lactamase family.
abstract: Antibiotic resistance in pathogenic bacteria is a major problem for human health. We analyzed metagenomic datasets from ancient and remote samples from diverse environmental sources and observed the presence of all the eleven antibiotic resistance genes (ARG) groups evaluated. Since ancient samples are not subjected to modern effects of antibiotic misuse, they represent a clean model to explore the natural diversity of ARG in the environment. Most sequences showed high divergence compared with known ARG, representing a much larger universe than the currently known and characterized ARGs. We explored whether proteins within the "divergent resistome" may correspond to functional ARG by characterizing a beta-lactamase hit with very low similarity to any known sequence (<45% to best BLAST hit in NCBI). By starting from purely in-silico data, we revived a new family of class B beta-lactamases from ancient medieval samples, which exhibited a very high penicillinase activity. In this work, we explored ancient resistomes and added novel support to previous works showing that the universe of ARG is naturally vast and diverse in microbial communities. Our results bring a new perspective to the exploration of environmental ARG and indicate that this gigantic reservoir represents a natural endless source of emerging resistances.
authors: Aix Marseille University, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
authors: Nicolás
authors: N
authors: Rascovan
authors: Aix Marseille University, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
authors: Amar
authors: A
authors: Telke
authors: Aix Marseille University, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.|Fédération de Microbiologie Clinique, Hôpital de la Timone, Marseille, France.
authors: Didier
authors: D
authors: Raoult
authors: Aix Marseille University, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.|Fédération de Microbiologie Clinique, Hôpital de la Timone, Marseille, France.
authors: Jean Marc
authors: JM
authors: Rolain
authors: Aix Marseille University, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
authors: Christelle
authors: C
authors: Desnues