Genome degradation promotes Salmonella pathoadaptation by remodeling fimbriae-mediated proinflammatory response

Xiao Zhou; Xiamei Kang; Jiaqi Chen; Yan Song; Chenghao Jia; Lin Teng; Yanting Tang; Zhijie Jiang; Xianqi Peng; Xiaoxi Tao; Yiwei Xu; Linlin Huang; Xuebin Xu; Yaohui Xu; Tengfei Zhang; Shenye Yu; Jiansen Gong; Shaohui Wang; Yuqing Liu; Guoqiang Zhu; Corinna Kehrenberg; François-Xavier Weill; Paul Barrow; Yan Li; Guoping Zhao; Min Yue

doi:10.1093/nsr/nwad228

Genome degradation promotes Salmonella pathoadaptation by remodeling fimbriae-mediated proinflammatory response

Natl Sci Rev. 2023 Sep 2;10(10):nwad228. doi: 10.1093/nsr/nwad228. eCollection 2023 Oct.

Authors

Xiao Zhou^{1

2}, Xiamei Kang¹, Jiaqi Chen¹, Yan Song¹, Chenghao Jia^{1

3}, Lin Teng¹, Yanting Tang¹, Zhijie Jiang¹, Xianqi Peng¹, Xiaoxi Tao¹, Yiwei Xu¹, Linlin Huang¹, Xuebin Xu⁴, Yaohui Xu⁵, Tengfei Zhang⁶, Shenye Yu⁷, Jiansen Gong⁸, Shaohui Wang⁹, Yuqing Liu¹⁰, Guoqiang Zhu¹¹, Corinna Kehrenberg¹², François-Xavier Weill¹³, Paul Barrow¹⁴, Yan Li^{1

3}, Guoping Zhao^{15

16

17}, Min Yue^{1

3

18

19}

Affiliations

¹ Institute of Preventive Veterinary Sciences and Department of Veterinary Medicine, Zhejiang University College of Animal Sciences, Hangzhou 310058, China.
² Ningbo Academy of Agricultural Sciences, Ningbo 315040, China.
³ Hainan Institute of Zhejiang University, Sanya 572025, China.
⁴ Department of Microbiology Laboratory, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China.
⁵ College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450053, China.
⁶ Key Laboratory of Prevention and Control Agents for Animal Bacteriosis, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.
⁷ Division of Bacterial Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
⁸ Poultry Institute, Chinese Academy of Agricultural Sciences, Yangzhou 225125, China.
⁹ Department of Animal Public Health, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
¹⁰ Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China.
¹¹ College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
¹² Institute for Veterinary Food Science, Faculty of Veterinary Medicine, Justus-Liebig University Giessen, Giessen 35392, Germany.
¹³ Institut Pasteur, Université Paris Cité, Unité des bactéries pathogènes entériques, Paris 75724, France.
¹⁴ School of Veterinary Medicine, University of Surrey, Guildford GU2 7AL, UK.
¹⁵ School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
¹⁶ CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
¹⁷ Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
¹⁸ State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
¹⁹ Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Hangzhou 310058, China.

Abstract

Understanding changes in pathogen behavior (e.g. increased virulence, a shift in transmission channel) is critical for the public health management of emerging infectious diseases. Genome degradation via gene depletion or inactivation is recognized as a pathoadaptive feature of the pathogen evolving with the host. However, little is known about the exact role of genome degradation in affecting pathogenic behavior, and the underlying molecular detail has yet to be examined. Using large-scale global avian-restricted Salmonella genomes spanning more than a century, we projected the genetic diversity of Salmonella Pullorum (bvSP) by showing increasingly antimicrobial-resistant ST92 prevalent in Chinese flocks. The phylogenomic analysis identified three lineages in bvSP, with an enhancement of virulence in the two recently emerged lineages (L2/L3), as evidenced in chicken and embryo infection assays. Notably, the ancestor L1 lineage resembles the Salmonella serovars with higher metabolic flexibilities and more robust environmental tolerance, indicating stepwise evolutionary trajectories towards avian-restricted lineages. Pan-genome analysis pinpointed fimbrial degradation from a virulent lineage. The later engineered fim-deletion mutant, and all other five fimbrial systems, revealed behavior switching that restricted horizontal fecal-oral transmission but boosted virulence in chicks. By depleting fimbrial appendages, bvSP established persistent replication with less proinflammation in chick macrophages and adopted vertical transovarial transmission, accompanied by ever-increasing intensification in the poultry industry. Together, we uncovered a previously unseen paradigm for remodeling bacterial surface appendages that supplements virulence-enhanced evolution with increased vertical transmission.

Keywords: Salmonella; fimbrial adhesin; host adaptation; pathogenic evolution; vertical transmission; virulence evolution.