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The complex resistomes of Paenibacillaceae reflect diverse antibiotic chemical ecologies

The ISME Journalvolume 12pages885897 (2018) | Download Citation

Abstract

The ecology of antibiotic resistance involves the interplay of a long natural history of antibiotic production in the environment, and the modern selection of resistance in pathogens through human use of these drugs. Important components of the resistome are intrinsic resistance genes of environmental bacteria, evolved and acquired over millennia, and their mobilization, which drives dissemination in pathogens. Understanding the dynamics and evolution of resistance across bacterial taxa is essential to address the current crisis in drug-resistant infections. Here we report the exploration of antibiotic resistance in the Paenibacillaceae prompted by our discovery of an ancient intrinsic resistome in Paenibacillus sp. LC231, recovered from the isolated Lechuguilla cave environment. Using biochemical and gene expression analysis, we have mined the resistome of the second member of the Paenibacillaceae family, Brevibacillus brevis VM4, which produces several antimicrobial secondary metabolites. Using phylogenomics, we show that Paenibacillaceae resistomes are in flux, evolve mostly independent of secondary metabolite biosynthetic diversity, and are characterized by cryptic, redundant, pseudoparalogous, and orthologous genes. We find that in contrast to pathogens, mobile genetic elements are not significantly responsible for resistome remodeling. This offers divergent modes of resistome development in pathogens and environmental bacteria.

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Acknowledgements

We thank Andrew McArthur (McMaster) and members of the CARD team for input into antibiotic resistance sequence analysis and interpretation of phylogenomic correlations. Computer server support provided by the laboratory of Dr. Andrew McArthur and the McMaster Service Lab and Repository (MSLR). We also thank Christine King (McMaster) for genome sequencing, Peter Spanogiannopoulos (UCSF) for early discussion on the rifampin phosphotransferases, and Julie Perry (University of Toronto) for early discussion on gene expression experiments. This research was funded by a Canadian Institutes of Health Research grant (FRN-148463) and by a Canada Research Chair in Antibiotic Biochemistry (to GDW).

Author contributions

ACP, ELW, and GDW designed research. ACP, ELW, KK, and NW performed research. ACP and GDW analyzed data. ACP performed the following experiments; antibiotic susceptibility testing, phylogenetics/phylogenomics, gene expression, growth curves, rifampin degradation studies, and in vitro enzyme assays except for MphJ. ELW performed the following experiments; cloning resistance genes, antibiotic susceptibility testing, and initial studies on gene expression. KK performed HPLC and high resolution mass spectrometry analysis of rifampin degradation. NW assembled the B. brevis VM4 genome and contributed to planning phylogenetics/phylogenomics experiments. ACP and GDW wrote the manuscript with input from all authors.

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  1. Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada

    • Andrew C. Pawlowski
    • , Erin L. Westman
    • , Kalinka Koteva
    • , Nicholas Waglechner
    •  & Gerard D. Wright

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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Gerard D. Wright.

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https://doi.org/10.1038/s41396-017-0017-5

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