Zhou Xiao, Kang Xiamei, Chen Jiaqi, Song Yan, Jia Chenghao, Teng Lin, Tang Yanting, Jiang Zhijie, Peng Xianqi, Tao Xiaoxi, Xu Yiwei, Huang Linlin, Xu Xuebin, Xu Yaohui, Zhang Tengfei, Yu Shenye, Gong Jiansen, Wang Shaohui, Liu Yuqing, Zhu Guoqiang, Kehrenberg Corinna, Weill François-Xavier, Barrow Paul, Li Yan, Zhao Guoping, Yue Min
Institute of Preventive Veterinary Sciences and Department of Veterinary Medicine, Zhejiang University College of Animal Sciences, Hangzhou 310058, China.
Ningbo Academy of Agricultural Sciences, Ningbo 315040, China.
Natl Sci Rev. 2023 Sep 2;10(10):nwad228. doi: 10.1093/nsr/nwad228. eCollection 2023 Oct.
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 genomes spanning more than a century, we projected the genetic diversity of 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 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 -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.
了解病原体行为的变化（例如毒力增加、传播途径转变）对于新发传染病的公共卫生管理至关重要。通过基因缺失或失活导致的基因组退化被认为是病原体与宿主共同进化的一种致病适应性特征。然而，关于基因组退化在影响致病行为的确切作用知之甚少，其潜在的分子细节仍有待研究。我们利用跨越一个多世纪的大规模全球禽类限制性基因组，通过展示在中国鸡群中普遍存在的对多种抗菌药物耐药的ST92，预测了鸡白痢沙门氏菌（bvSP）的遗传多样性。系统基因组分析在bvSP中鉴定出三个谱系，在鸡和胚胎感染试验中证明，最近出现的两个谱系（L2/L3）的毒力有所增强。值得注意的是，祖先L1谱系类似于具有更高代谢灵活性和更强环境耐受性的血清型，表明向禽类限制性谱系的逐步进化轨迹。泛基因组分析确定了一个有毒力谱系的菌毛退化。后来构建的菌毛缺失突变体以及所有其他五个菌毛系统，显示出行为转变，即限制水平粪-口传播，但增强了雏鸡的毒力。通过去除菌毛附属物，bvSP在雏鸡巨噬细胞中建立了持续复制，炎症反应较少，并采用垂直经卵传播，同时伴随着家禽业的不断强化。总之，我们发现了一种以前未见过的重塑细菌表面附属物的模式，该模式通过增加垂直传播来补充毒力增强的进化。
