Characterization of Cph Homologues Reveals Widespread Capreomycin Resistance Genes in Nature

Shu-Ing Toh (卓淑鶯) 1,2, Elaine Keisha Johan 3, Chin-Yuan Chang 1,2

1Department of Biological Science and Technology, National Yang Ming Chiao Tung University

2Institute of Molecular Medicine and Bioengineering, National Yang Ming Chiao Tung University

3Department of Otolaryngology, National Taiwan University Hospital

Metagenomic-based studies have predicted abundant potential antibiotic-resistant genes (ARGs) according to the DNA/protein sequence identity. These ARGs are hidden in various environmental bacteria and may become a latent crisis for antibiotic therapy via horizontal gene transfer. In this study, we focus on a resistance gene cph, which encodes a phosphotransferase (Cph), conferring resistance to an antituberculosis drug capreomycin (CMN). Sequence Similarity Network classified 353 Cph homologues into five major clusters, where the authentic function and targeted antibiotic of these putative resistance proteins in the cluster I were examined via bioinformatics, biochemical, and protein structural analysis. The result revealed that the resistance genes against CMN are widespread in various species and confer resistance to CMN. This study sets the stage for the investigation of ARGs in nature and contributes towards understanding the sequence-structure-function relationships of the putative resistance genes