Serine/threonine protein kinase mediates rifampicin resistance in Brucella melitensis through interacting with ribosomal protein RpsD and affecting antioxidant capacity
ABSTRACT Brucellosis, a zoonotic disease, has re-emerged in both humans and animals, causing significant economic losses globally. Recently, an increasing number of rifampicin-resistant Brucella strains have been isolated worldwide without detectable mutations in known antibiotic resistance genes. H...
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American Society for Microbiology
2025-01-01
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| Series: | mSystems |
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| Online Access: | https://journals.asm.org/doi/10.1128/msystems.01109-24 |
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| author | Yaqin Yuan Wenqing Ning Junjie Chen Jiquan Li Tianqi Xue Cuihong An Lingling Mao Guangzhi Zhang Shizhong Zhou Jiabo Ding Xiaowen Yang Jianqiang Ye |
| author_facet | Yaqin Yuan Wenqing Ning Junjie Chen Jiquan Li Tianqi Xue Cuihong An Lingling Mao Guangzhi Zhang Shizhong Zhou Jiabo Ding Xiaowen Yang Jianqiang Ye |
| author_sort | Yaqin Yuan |
| collection | DOAJ |
| description | ABSTRACT Brucellosis, a zoonotic disease, has re-emerged in both humans and animals, causing significant economic losses globally. Recently, an increasing number of rifampicin-resistant Brucella strains have been isolated worldwide without detectable mutations in known antibiotic resistance genes. Here, this study identified the deletion of serine/threonine protein kinase (STPK) gene in B. melitensis as an efficient trigger for rifampicin resistance using bioinformatics predictions, a transposon mutant library, and gene mutation strains. Notably, the absence of the STPK could increase the expression of ribosomal proteins and genes involved in sulfur metabolism and reduced glutathione, and decrease NADPH oxidase activity and NADP+/NADPH ratio, which is associated with the antioxidant capacity of B. melitensis. Moreover, co-immunoprecipitation revealed that STPK could efficiently interact with the ribosomal protein RpsD, possibly altering protein translation and riboswitch expression. These findings demonstrate that the STPK gene mediates resistance by regulating sulfur metabolism to counteract the reactive oxygen species induced by rifampicin. Furthermore, the approaches developed in this study provide a platform for screening new resistance genes in Brucella spp., and the identified STPK or its pathway can serve as a potential target for new drug development against rifampicin-resistant Brucella spp.IMPORTANCENew rifampicin resistance gene in Brucella melitensis is identified via bioinformatics predictions and a whole-genome transposon mutant library, new mechanisms of rifampicin resistance in B. melitensis, and new function of serine/threonine protein kinase gene and its interaction proteins. |
| format | Article |
| id | doaj-art-83e668bc8dea40b3bf7828b1b422a12a |
| institution | Kabale University |
| issn | 2379-5077 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj-art-83e668bc8dea40b3bf7828b1b422a12a2025-01-21T14:00:28ZengAmerican Society for MicrobiologymSystems2379-50772025-01-0110110.1128/msystems.01109-24Serine/threonine protein kinase mediates rifampicin resistance in Brucella melitensis through interacting with ribosomal protein RpsD and affecting antioxidant capacityYaqin Yuan0Wenqing Ning1Junjie Chen2Jiquan Li3Tianqi Xue4Cuihong An5Lingling Mao6Guangzhi Zhang7Shizhong Zhou8Jiabo Ding9Xiaowen Yang10Jianqiang Ye11Jiangsu Key Laboratory of Zoonosis, Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine of Ministry of Education, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaKey Laboratory of Animal Biosafe Risk Prevention and Control (North), Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, ChinaTongliao Mongolian Medical Hospital (Tongliao Mongolian Medical Research Institute), China Center for Disease Control and Prevention, Institute of Infectious Disease Control and Prevention, Co-construction research base for brucellosis, Tongliao City, ChinaQinghai Institute for Endemic Disease Prevention and Control, Xining, ChinaJiangsu Key Laboratory of Zoonosis, Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine of Ministry of Education, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaDepartment of Plague and Brucellosis, Shaanxi Center for Disease Control and Prevention, Xi’an, ChinaLiaoning Province Center for Disease Control and Prevention, Shenyang, ChinaKey Laboratory of Animal Biosafe Risk Prevention and Control (North), Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, ChinaKey Laboratory of Animal Biosafe Risk Prevention and Control (North), Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, ChinaKey Laboratory of Animal Biosafe Risk Prevention and Control (North), Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, ChinaKey Laboratory of Animal Biosafe Risk Prevention and Control (North), Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, ChinaJiangsu Key Laboratory of Zoonosis, Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine of Ministry of Education, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaABSTRACT Brucellosis, a zoonotic disease, has re-emerged in both humans and animals, causing significant economic losses globally. Recently, an increasing number of rifampicin-resistant Brucella strains have been isolated worldwide without detectable mutations in known antibiotic resistance genes. Here, this study identified the deletion of serine/threonine protein kinase (STPK) gene in B. melitensis as an efficient trigger for rifampicin resistance using bioinformatics predictions, a transposon mutant library, and gene mutation strains. Notably, the absence of the STPK could increase the expression of ribosomal proteins and genes involved in sulfur metabolism and reduced glutathione, and decrease NADPH oxidase activity and NADP+/NADPH ratio, which is associated with the antioxidant capacity of B. melitensis. Moreover, co-immunoprecipitation revealed that STPK could efficiently interact with the ribosomal protein RpsD, possibly altering protein translation and riboswitch expression. These findings demonstrate that the STPK gene mediates resistance by regulating sulfur metabolism to counteract the reactive oxygen species induced by rifampicin. Furthermore, the approaches developed in this study provide a platform for screening new resistance genes in Brucella spp., and the identified STPK or its pathway can serve as a potential target for new drug development against rifampicin-resistant Brucella spp.IMPORTANCENew rifampicin resistance gene in Brucella melitensis is identified via bioinformatics predictions and a whole-genome transposon mutant library, new mechanisms of rifampicin resistance in B. melitensis, and new function of serine/threonine protein kinase gene and its interaction proteins.https://journals.asm.org/doi/10.1128/msystems.01109-24Brucellarifampicin resistanceSTPKrpsDsulfur metabolism |
| spellingShingle | Yaqin Yuan Wenqing Ning Junjie Chen Jiquan Li Tianqi Xue Cuihong An Lingling Mao Guangzhi Zhang Shizhong Zhou Jiabo Ding Xiaowen Yang Jianqiang Ye Serine/threonine protein kinase mediates rifampicin resistance in Brucella melitensis through interacting with ribosomal protein RpsD and affecting antioxidant capacity mSystems Brucella rifampicin resistance STPK rpsD sulfur metabolism |
| title | Serine/threonine protein kinase mediates rifampicin resistance in Brucella melitensis through interacting with ribosomal protein RpsD and affecting antioxidant capacity |
| title_full | Serine/threonine protein kinase mediates rifampicin resistance in Brucella melitensis through interacting with ribosomal protein RpsD and affecting antioxidant capacity |
| title_fullStr | Serine/threonine protein kinase mediates rifampicin resistance in Brucella melitensis through interacting with ribosomal protein RpsD and affecting antioxidant capacity |
| title_full_unstemmed | Serine/threonine protein kinase mediates rifampicin resistance in Brucella melitensis through interacting with ribosomal protein RpsD and affecting antioxidant capacity |
| title_short | Serine/threonine protein kinase mediates rifampicin resistance in Brucella melitensis through interacting with ribosomal protein RpsD and affecting antioxidant capacity |
| title_sort | serine threonine protein kinase mediates rifampicin resistance in brucella melitensis through interacting with ribosomal protein rpsd and affecting antioxidant capacity |
| topic | Brucella rifampicin resistance STPK rpsD sulfur metabolism |
| url | https://journals.asm.org/doi/10.1128/msystems.01109-24 |
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