Shen Cong, Zeng Jinxiang, Zheng Dexiang, Xiao Yinglun, Pu Jieying, Luo Li, Zhou Hongyun, Cai Yimei, Zhang Liling, Wu Meina, Zhang Xuan, Deng Guangyuan, Li Song, Li Qiwei, Zeng Jianming, Sun Zhaohui, Huang Bin, Chen Cha
The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Clinical Laboratory, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China.
Microbiol Spectr. 2023 Sep 28;11(5):e0531222. doi: 10.1128/spectrum.05312-22.
() is one of the leading causes of chronic infections, including reinfection, relapse, and persistent infection, especially in cystic fibrosis patients. Relapse infections are more harmful because of repeated hospitalization and undertreatment of antimicrobials. However, relapse infection in China remains largely unknown. Herein, we performed a 3-year retrospective study from 2019 to 2022 in a tertiary hospital, which included 442 . isolates from 196 patients. Relapse infection was identified by screening clinical records and whole-genome sequencing (WGS). We found that 31.6% (62/196) of patients had relapsed infections. The relapse incidence of carbapenem-resistant infection (51.4%) is significantly higher than that of carbapenem-susceptible infection (20.2%, < 0.0001). These isolates were assigned to 50 distinct sequence types and sporadically distributed in phylogeny, indicating that relapsed infections were not caused by certain lineages. Fast adaptation and evolution of isolates were reflected by dynamic changes of antimicrobial resistance, gene loss and acquisition, and single-nucleotide polymorphisms during relapse episodes. Remarkably, a convergent non-synonymous mutation that occurs in a pyochelin-associated virulence gene (T1056C, M252T) could be a considerable target for the diagnosis and treatment of relapse infection. These findings suggest that integrated utilization of WGS and medical records provides opportunities for improved diagnostics of relapsed infections. Continued surveillance of the genomic dynamics of relapse infection will generate further knowledge for optimizing treatment and prevention in the future.IMPORTANCE is a predominant pathogen that causes various chronic infections. Relapse infections promote the adaptation and evolution of antimicrobial resistance and virulence of , which obscure evolutionary trends and complicate infection management. We observed a high incidence of relapse infection in this study. Whole-genome sequencing (WGS) revealed that relapse infections were not caused by certain lineages of isolates. Genomic dynamics of relapse among early and later stages reflected a plasticity scattered through the entire genome and fast adaptation and genomic evolution in different ways. Remarkably, a convergent evolution was found in a significant virulence gene fptA, which could be a considerable target for diagnosis and treatment. Taken together, our findings highlight the importance of longitudinal surveillance of relapse infection in China since cystic fibrosis is rare in Chinese. Integrated utilization of WGS and medical records provides opportunities for improved diagnostics of relapse infections.
（）是慢性感染的主要原因之一，包括再感染、复发和持续感染，尤其是在囊性纤维化患者中。复发感染由于反复住院和抗菌药物治疗不足而更具危害性。然而，中国的复发感染情况在很大程度上仍不为人知。在此，我们在一家三级医院进行了一项从2019年到2022年的为期3年的回顾性研究，其中包括来自196名患者的442株 分离株。通过筛查临床记录和全基因组测序（WGS）来确定复发感染。我们发现31.6%（62/196）的患者发生了复发感染。耐碳青霉烯类 感染的复发率（51.4%）显著高于对碳青霉烯类敏感的 感染（20.2%，<0.0001）。这些分离株被分为50种不同的序列类型，在系统发育中呈散在分布，这表明复发感染不是由某些谱系引起的。复发期间抗菌药物耐药性的动态变化、基因的丢失和获得以及单核苷酸多态性反映了 分离株的快速适应和进化。值得注意的是，在一种与绿脓菌素相关的毒力基因 （T1056C，M252T）中发生的趋同非同义突变可能是复发 感染诊断和治疗的一个重要靶点。这些发现表明，WGS和病历的综合利用为改善复发感染的诊断提供了机会。对复发 感染的基因组动态进行持续监测将为未来优化治疗和预防产生更多知识。重要性 是引起各种慢性感染的主要病原体。复发感染促进了 的抗菌药物耐药性和毒力的适应和进化，这掩盖了进化趋势并使感染管理复杂化。我们在本研究中观察到较高的复发 感染发生率。全基因组测序（WGS）显示，复发感染不是由 分离株的某些谱系引起的。早期和后期复发 的基因组动态反映了整个基因组中分散的可塑性以及以不同方式的快速适应和基因组进化。值得注意的是，在一个重要的毒力基因fptA中发现了趋同进化，这可能是诊断和治疗的一个重要靶点。综上所述，我们的研究结果突出了在中国对复发 感染进行纵向监测的重要性，因为囊性纤维化在中国较为罕见。WGS和病历的综合利用为改善复发感染的诊断提供了机会。
