Discovery and characterization of genes conferring natural resistance to the antituberculosis antibiotic capreomycin

Shu Ing Toh; Johan Elaine Keisha; Yung Lin Wang; Yi Chi Pan; Yu Heng Jhu; Po Yun Hsiao; Wen Ting Liao; Po Yuan Chen; Tai Ming Ko; Chin Yuan Chang

doi:10.1038/s42003-023-05681-6

Discovery and characterization of genes conferring natural resistance to the antituberculosis antibiotic capreomycin

Shu Ing Toh, Johan Elaine Keisha, Yung Lin Wang, Yi Chi Pan, Yu Heng Jhu, Po Yun Hsiao, Wen Ting Liao, Po Yuan Chen, Tai Ming Ko, Chin Yuan Chang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Metagenomic-based studies have predicted an extraordinary number of potential antibiotic-resistance genes (ARGs). 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) that confers resistance to the antituberculosis drug capreomycin (CMN). Sequence Similarity Network (SSN) analysis classified 353 Cph homologues into five major clusters, where the proteins in cluster I were found in a broad range of actinobacteria. We examine the function and antibiotics targeted by three putative resistance proteins in cluster I via biochemical and protein structural analysis. Our findings reveal that these three proteins in cluster I confer resistance to CMN, highlighting an important aspect of CMN resistance within this gene family. This study contributes towards understanding the sequence-structure-function relationships of the phosphorylation resistance genes that confer resistance to CMN.

Original language	English
Article number	1282
Journal	Communications Biology
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s42003-023-05681-6
State	Published - Dec 2023

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title = "Discovery and characterization of genes conferring natural resistance to the antituberculosis antibiotic capreomycin",

abstract = "Metagenomic-based studies have predicted an extraordinary number of potential antibiotic-resistance genes (ARGs). 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) that confers resistance to the antituberculosis drug capreomycin (CMN). Sequence Similarity Network (SSN) analysis classified 353 Cph homologues into five major clusters, where the proteins in cluster I were found in a broad range of actinobacteria. We examine the function and antibiotics targeted by three putative resistance proteins in cluster I via biochemical and protein structural analysis. Our findings reveal that these three proteins in cluster I confer resistance to CMN, highlighting an important aspect of CMN resistance within this gene family. This study contributes towards understanding the sequence-structure-function relationships of the phosphorylation resistance genes that confer resistance to CMN.",

author = "Toh, {Shu Ing} and {Elaine Keisha}, Johan and Wang, {Yung Lin} and Pan, {Yi Chi} and Jhu, {Yu Heng} and Hsiao, {Po Yun} and Liao, {Wen Ting} and Chen, {Po Yuan} and Ko, {Tai Ming} and Chang, {Chin Yuan}",

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doi = "10.1038/s42003-023-05681-6",

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AU - Toh, Shu Ing

AU - Elaine Keisha, Johan

AU - Wang, Yung Lin

AU - Pan, Yi Chi

AU - Jhu, Yu Heng

AU - Hsiao, Po Yun

AU - Liao, Wen Ting

AU - Chen, Po Yuan

AU - Ko, Tai Ming

AU - Chang, Chin Yuan

PY - 2023/12

Y1 - 2023/12

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Discovery and characterization of genes conferring natural resistance to the antituberculosis antibiotic capreomycin

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