Joao Gatica Arias edited AbstractImportanceIntroductionHistorically_b_lactam_antibiotics_are__.html  over 7 years ago

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author = {Thomas P Van Boeckel and Sumanth Gandra and Ashvin Ashok and Quentin Caudron and Bryan T Grenfell and Simon A Levin and Ramanan Laxminarayan},  title = {Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data},  journal = {The Lancet Infectious Diseases}  }" data-bib-key="Van_Boeckel_2014" contenteditable="false">Boeckel 2014 ESAC 2009, ECDC 2012), but the successful of antibiotic treatments is compromised by the development of resistance in many important clinical pathogens (class="squire-citation ltx_cite" class="ltx_cite"  data-bib-text="@article{Davies_2010, doi = {10.1128/mmbr.00016-10},  url = {http://dx.doi.org/10.1128/mmbr.00016-10},  year = 2010, 

author = {J. Davies and D. Davies},  title = {Origins and Evolution of Antibiotic Resistance},  journal = {Microbiology and Molecular Biology Reviews}  }" data-bib-key="Davies_2010" contenteditable="false" style="cursor: pointer"> contenteditable="false">  href="#Davies_2010">Davies 2010
). The major cause of resistance to b-lactams antibiotics are bacterial enzymes called b-lactamases with the capacity to hydrolyze the molecular structure of the b-lactam antibiotic ( ...
author = {Rebecca Sullivan and David Schaus},  title = {Extended Spectrum Beta- Lactamases: A Minireview of Clinical Relevant Groups},  journal = {Journal of Medical Microbiology {\&} Diagnosis}  }" data-bib-key="Sullivan_2015" contenteditable="false">Sullivan 2015
), but no enough  efforts have been put in assess b-lactamases in non-clinical settings.

Studies assessing the AR phenomenon in non-clinical environments usually are based on functional metagenomics studies, PCR reactions, MIC tests ( ...
author = {Dennis Versluis and Marco Maria D'Andrea and Javier Ramiro Garcia and Milkha M. Leimena and Floor Hugenholtz and Jing Zhang and Ba{\c{s}}ak Öztürk and Lotta Nylund and Detmer Sipkema and Willem van Schaik and Willem M. de Vos and Michiel Kleerebezem and Hauke Smidt and Mark W.J. van Passel},  title = {Mining microbial metatranscriptomes for expression of antibiotic resistance genes under natural conditions},  journal = {Sci. Rep.}  }" data-bib-key="Versluis_2015" contenteditable="false">Versluis 2015
) that cannot be ignored.

Despite that in the last years more studies are focused on ARGs in the environment, environment (Czekalski 2015, Bhullar 2012, Cristóbal-Azkarate 2014, Nesme 2014, Karkman 2016),  the lack of studies focused  on b-lactamases the high diversity of b-lactamase genes  in different environments, avoid the understanding of important process with clinical implications such as b-lactamase gene transfer between environments and the impact of anthropogenic forces on both b-lactamase content and diversity in natural environments.

In this study we assess the presence and diversity of b-lacatamases in different environments through a wide metagenomic approach and network oriented analysis, providing important findings on the pool of b-lactamase genes in different environments. 



Results

A effort to understand the scope of b-lactam resistance in the environment was performed through a global survey of b-lactamases present in 232 shotgun metagenomes. Metagenomic data sets were obtained from two important public repositories. These data sets  account for 770 Gigabytes of information and more than 4.7 billion of metagenomic reads (details can be found in table S1); and are related to different environments such as agricultural soils, non-agricultural soils, glaciers, fresh water, oceans, human gut, cow feces, cow rumen and wastewater treatment plant environment. The metagenomic reads were compared to the EX-B database; a database that include more than 1500 b-lactamases (for details see material and methods). Metagenomic reads containing b-lactamases were identified by BLASTX  based on their similarity to the EX-B database at the cutoff thresholds described in material and methods (i.e.  percent of identity equal o higher than 50%, e-value equal or lower than \(10^{-5}\), and a bit score equal o higher than 30). Environmental b-lactamases can be diverse relative to clinically characterized b-lactamases (