Identification of a novel linezolid resistance gene, cfr(F), in Riemerella anatipestifer

doi:10.1016/j.jia.2025.11.026

Advanced Online Publication | Current Issue | Archive | Adv Search

Yihua Zhang¹^,²^,^{3, 4}, Zhishuang Yang¹^,²^,^{3, 4}, Mingshu Wang¹^,²^,³^,⁴^,⁵, Renyong Jia¹^,²^,³^,⁴^,⁵, Shun Chen¹^,²^,³^,⁴^,⁵, Mafeng Liu¹^,²^,³^,⁴^,⁵, Xinxin Zhao¹^,²^,³^,⁴^,⁵, Qiao Yang¹^,²^,³^,⁴^,⁵, Ying Wu¹^,²^,³^,⁴^,⁵, Shaqiu Zhang¹^,²^,³^,⁴^,⁵, Juan Huang¹^,²^,³^,⁴^,⁵, Xumin Ou¹^,²^,³^,⁴^,⁵, Di Sun¹^,²^,³^,⁴^,⁵, Bin Tian¹^,²^,³^,⁴^,⁵, Yu He¹^,²^,³^,⁴^,⁵, Zhen Wu¹^,²^,³^,⁴^,⁵, Anchun Cheng¹^,⁴^,⁵^,⁶^#, Dekang Zhu¹^,²^,³^,⁴^,⁵^#

¹Research Center of Avian Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

²Agricultural Animal Diseases and Veterinary Public Health Key Laboratory of Sichuan Province, Chengdu 611130, China.

³Key Laboratory of Agricultural Bioinformatics, Ministry of Education, Ministry of Education of the People's Republic of China, Chengdu 611130, China.

⁴International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, China.

⁵Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, China.

⁶Institute of Veterinary Immunology and Green Drugs/Veterinary Department in College of Animal Science/State Key Laboratory of Green Pesticide, Guizhou University, Guiyang 550025, China

Highlights

• A novel linezolid resistance gene, cfr(F), was identified in R. anatipestifer.

• cfr(F) confers cross-resistance to PhLOPS_A antibiotics, including linezolid.

• R. anatipestifer is a potential reservoir for linezolid resistance gene dissemination.

Abstract
References

Download: PDF in ScienceDirect
Export: BibTeX | EndNote (RIS)

摘要

抗生素耐药性仍是人类与兽医学领域面临的最严峻挑战之一。鸭疫里默氏菌是一种重要的禽类病原，已被证实具有多重耐药性。本研究通过全基因组测序，从鸭疫里默氏菌临床菌株RCAD1242中鉴定并表征了一个新型利奈唑胺耐药基因cfr(F)。通过将cfr(F)克隆至敏感株鸭疫里默氏菌ATCC 11845与多杀性巴氏杆菌DY120818并进行药敏试验，证实该基因可介导对酰胺醇类、林可酰胺类、恶唑烷酮类、截短侧耳素及A型链阳菌素的交叉耐药，即PhLOPS_A表型。其氨基酸序列与已报道的cfr基因的相似性仅为32.9%-43.8%。重组菌株对氟苯尼考、利奈唑胺等抗生素的最小抑菌浓度（MIC）提升2-1024倍。目前cfr(F)基因已在中国、韩国和美国被检出，呈现跨地域传播的趋势。鉴于鸭疫里默氏菌在家禽广泛流行并具备可移动遗传元件交换能力，该菌可能成为恶唑烷酮类耐药性向临床重要人类病原菌传播的潜在储存库，构成公共卫生威胁。本研究强调应加强“同一健康（One Health）”框架下的耐药性监测体系，并在动物、环境、人类领域推行科学、审慎的抗菌药物使用策略，以遏制耐药基因的跨物种传播。

Online: 14 November 2025

Fund:

This work was supported by the National Key Research and Development Program of China (2023YFD1800200), the Key Program of the National Natural Science Foundation of China (U24A20451), the Earmarked Fund for China Agriculture Research System（CARS-42-17), the Sichuan Veterinary Medicine and the Drug Innovation Group of China Agricultural Research System (SCCXTD-2025-18).

About author: Yihua Zhang, E-mail: zyh18881577639@163.com; #Correspondence Dekang Zhu, E-mail: zdk24@sicau.edu.cn; Anchun Cheng, E-mail: chenganchun@vip.163.com

	Service
	E-mail this article
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors

Cite this article:

Yihua Zhang, Zhishuang Yang, Mingshu Wang, Renyong Jia, Shun Chen, Mafeng Liu, Xinxin Zhao, Qiao Yang, Ying Wu, Shaqiu Zhang, Juan Huang, Xumin Ou, Di Sun, Bin Tian, Yu He, Zhen Wu, Anchun Cheng, Dekang Zhu. 2025. Identification of a novel linezolid resistance gene, cfr(F), in Riemerella anatipestifer. Journal of Integrative Agriculture, Doi:10.1016/j.jia.2025.11.026

Alcock B P, Huynh W, Chalil R, Smith K W, Raphenya A R, Wlodarski M A, Edalatmand A, Petkau A, Syed S A, Tsang K K, Baker S J C, Dave M, Mccarthy M C, Mukiri K M, Nasir J A, Golbon B, Imtiaz H, Jiang X, Kaur K, Kwong M, et al. 2022. CARD 2023: expanded curation, support for machine learning, and resistome prediction at the Comprehensive Antibiotic Resistance Database. Nucleic Acids Research, 51, D690-D699.

Candela T, Marvaud J-C, Nguyen T K, Lambert T. 2017. A cfr-like gene cfr(C) conferring linezolid resistance is common in Clostridium difficile. International Journal of Antimicrobial Agents, 50, 496-500.

CLSI. 2023. Performance Standards for Antimicrobial Susceptibility Testing, M100 33rd Edition. Clinical and Laboratory Standards Institute, Wayne, PA.

Deshpande L M, Ashcraft D S, Kahn H P, Pankey G, Jones R N, Farrell D J, Mendes R E. 2015. Detection of a New cfr-Like Gene, cfr(B), in Enterococcus faecium Isolates Recovered from Human Specimens in the United States as Part of the SENTRY Antimicrobial Surveillance Program. Antimicrobial Agents and Chemotherapy, 59, 6256-6261.

Feldgarden M, Brover V, Haft D H, Prasad A B, Slotta D J, Tolstoy I, Tyson G H, Zhao S, Hsu C-H, Mcdermott P F, Tadesse D A, Morales C, Simmons M, Tillman G, Wasilenko J, Folster J P, Klimke W. 2019. Validating the AMRFinder Tool and Resistance Gene Database by Using Antimicrobial Resistance Genotype-Phenotype Correlations in a Collection of Isolates. Antimicrobial Agents and Chemotherapy, 63, e00483-19.

Guerin F, Sassi M, Dejoies L, Zouari A, Schutz S, Potrel S, Auzou M, Collet A, Lecointe D, Auger G, Cattoir V. 2020. Molecular and functional analysis of the novel cfr(D) linezolid resistance gene identified in Enterococcus faecium. Journal of Antimicrobial Chemotherapy, 75, 1699-1703.

Huang L, Liu M, Ammanath A V, Zhu D, Jia R, Chen S, Zhao X, Yang Q, Wu Y, Zhang S, Huang J, Ou X, Mao S, Gao Q, Sun D, Tian B, Götz F, Wang M, Cheng A. 2021. Identification of the Natural Transformation Genes in Riemerella anatipestifer by Random Transposon Mutagenesis. Frontiers in Microbiology, 12, 712198.

Liu M, Zhang L, Huang L, Biville F, Zhu D, Wang M, Jia R, Chen S, Sun K, Yang Q, Wu Y, Chen X, Cheng A. 2017a. Use of Natural Transformation To Establish an Easy Knockout Method in Riemerella anatipestifer. Applied and Environmental Microbiology, 83, e00127-17.

Liu X-Q, Wang J, Li W, Zhao L-Q, Lu Y, Liu J-H, Zeng Z-L. 2017b. Distribution of cfr in Staphylococcus spp. and Escherichia coli Strains from Pig Farms in China and Characterization of a Novel cfr-Carrying F43:A-:B- Plasmid. Frontiers in Microbiology, 8, 329.

Long K S, Poehlsgaard J, Kehrenberg C, Schwarz S, Vester B. 2006. The Cfr rRNA methyltransferase confers resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics. Antimicrobial Agents and Chemotherapy, 50, 2500-2505.

Luo H, Li M, Yang Z, Zhu D, Li P. 2022. Characterization of RASA-1, a novel class A extended-spectrum beta-lactamase from Riemerella anatipestifer. Veterinary Microbiology, 270, 109456.

Madeira F, Madhusoodanan N, Lee J, Eusebi A, Niewielska A, Tivey A R N, Lopez R, Butcher S. 2024. The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024. Nucleic Acids Research, 52, W521-W525.

Polikanov Y S, Starosta A L, Juette M F, Altman R B, Terry D S, Lu W, Burnett B J, Dinos G, Reynolds K A, Blanchard S C, Steitz T A, Wilson D N. 2015. Distinct tRNA Accommodation Intermediates Observed on the Ribosome with the Antibiotics Hygromycin A and A201A. Molecular Cell, 58, 832-844.

Roberts M C, Sutcliffe J, Courvalin P, Jensen L B, Rood J, Seppala H. 1999. Nomenclature for Macrolide and Macrolide-Lincosamide-Streptogramin B Resistance Determinants. Antimicrobial Agents and Chemotherapy, 43, 2823-2830.

Schwarz S, Werckenthin C, Kehrenberg C. 2000a. Identification of a plasmid-borne chloramphenicol-florfenicol resistance gene in Staphylococcus sciuri. Antimicrobial Agents and Chemotherapy, 44, 2530-2533.

Schwarz S, Werckenthin C, Kehrenberg C. 2000b. Identification of a Plasmid-Borne Chloramphenicol-Florfenicol Resistance Gene in Staphylococcus sciuri. Antimicrobial Agents and Chemotherapy, 44, 2530-2533.

Schwarz S, Zhang W, Du X-D, Krüger H, Feßler A T, Ma S, Zhu Y, Wu C, Shen J, Wang Y. 2021. Mobile Oxazolidinone Resistance Genes in Gram-Positive and Gram-Negative Bacteria. Clinical Microbiology Reviews, 34, 10.1128/cmr.00188-00120.

Shen J, Wang Y, Schwarz S. 2013. Presence and dissemination of the multiresistance gene cfr in Gram-positive and Gram-negative bacteria. Journal of Antimicrobial Chemotherapy, 68, 1697-1706.

Smith L K, Mankin A S. 2008. Transcriptional and translational control of the mlr operon, which confers resistance to seven classes of protein synthesis inhibitors. Antimicrobial Agents and Chemotherapy, 52, 1703-1712.

Stojković V, Ulate M F, Hidalgo-Villeda F, Aguilar E, Monge-Cascante C, Pizarro-Guajardo M, Tsai K, Tzoc E, Camorlinga M, Paredes-Sabja D, Quesada-Gómez C, Fujimori D G, Rodríguez C. 2019. cfr(B), cfr(C), and a New cfr-Like Gene, cfr(E), in Clostridium difficile Strains Recovered across Latin America. Antimicrobial Agents and Chemotherapy, 64, e01074-19.

Tang Y, Dai L, Sahin O, Wu Z, Liu M, Zhang Q. 2017. Emergence of a plasmid-borne multidrug resistance gene cfr(C) in foodborne pathogen Campylobacter. Journal of Antimicrobial Chemotherapy, 72, 1581-1588.

Tao M, Wang J, Li K, Xue Y, Xu X, Du X, He X, Tian X, Zou Z, Hu Z, Islam N, Hu Q. 2020. Development of signature-tagged mutagenesis in Riemerella anatipestifer to identify genes essential for survival and pathogenesis. Veterinary Microbiology, 250, 108857.

Umar Z, Chen Q, Tang B, Xu Y, Wang J, Zhang H, Ji K, Jia X, Feng Y. 2021. The poultry pathogen Riemerella anatipestifer appears as a reservoir for Tet(X) tigecycline resistance. Environmental Microbiology, 23, 7465-7482.

Vester B. 2018. The cfr and cfr-like multiple resistance genes. Research in Microbiology, 169, 61-66.

Yang Z, Wang M, Jia R, Chen S, Liu M, Zhao X, Yang Q, Wu Y, Zhang S, Huang J, Ou X, Mao S, Gao Q, Sun D, Tian B, He Y, Wu Z, Zhu D, Cheng A. 2024. Genome-based assessment of antimicrobial resistance reveals the lineage specificity of resistance and resistance gene profiles in Riemerella anatipestifer from China. Microbiology Spectrum, 12, e03132-03123.

Zhu D, Wei X, Zhu H, Yang Z, Wang M, Jia R, Chen S, Liu M, Zhao X, Yang Q, Wu Y, Zhang S, Huang J, Ou X, Mao S, Gao Q, Sun D, Tian B, Cheng A. 2022. Emergence of plasmid-mediated tigecycline, β-lactam and florfenicol resistance genes tet(X), bla_OXA-347 and floR in Riemerella anatipestifer isolated in China. Poultry Science, 101, 102057.

Zhu D, Yang Z, Xu J, Wang M, Jia R, Chen S, Liu M, Zhao X, Yang Q, Wu Y, Zhang S, Liu Y, Zhang L, Yu Y, Chen X, Cheng A. 2020. Pan-genome analysis of Riemerella anatipestifer reveals its genomic diversity and acquired antibiotic resistance associated with genomic islands. Functional & Integrative Genomics, 20, 307-320.

No related articles found!

No Suggested Reading articles found!

Viewed

Full text

Abstract

Cited

Shared

Discussed

Cite this article:

About JIA

Editorial board

For authors