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肺炎患儿与健康对照中非可分型的比较基因组研究。

Comparative genomic study of non-typeable in children with pneumonia and healthy controls.

作者信息

Zhang Deming, Wang Wenjian, Song Chunli, Huang Tingting, Chen Hongyu, Liu Zihao, Zhou Yiwen, Wang Heping

机构信息

Shantou University Medical College, Shantou University, Shantou, Guangdong 515041, China.

Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, China.

出版信息

iScience. 2024 Nov 6;27(12):111330. doi: 10.1016/j.isci.2024.111330. eCollection 2024 Dec 20.

DOI:10.1016/j.isci.2024.111330
PMID:39650731
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11625288/
Abstract

Non-typeable (NTHi) is a common pathogen causing respiratory infections, including pneumonia in children, and can also be found in the upper respiratory tracts of asymptomatic individuals. This study examines genomic variations between NTHi strains from healthy children and those from children with acute or chronic community-acquired pneumonia (CAP). Using bacterial genome-wide association studies (bGWAS), we compared these strains to identify key differences. Our analysis revealed that approximately 32% of genes exhibit variations between commensal and pathogenic states. Notably, we identified changes in pathways and significant virulence factors associated with pneumonia. Furthermore, we observed a significant difference in β-lactam resistance due to PBP3 mutations between the healthy and pneumonia groups, confirmed by the ampicillin susceptibility test and characterized by the mutation pattern D350N, S357N, S385T, L389F. These findings contribute valuable insights into the genomic basis of NTHi pathogenicity and may inform more targeted clinical diagnostics and treatments.

摘要

不可分型流感嗜血杆菌(NTHi)是引起呼吸道感染的常见病原体,包括儿童肺炎,也可在无症状个体的上呼吸道中发现。本研究检测了健康儿童与急性或慢性社区获得性肺炎(CAP)儿童的NTHi菌株之间的基因组变异。我们使用细菌全基因组关联研究(bGWAS)对这些菌株进行比较,以确定关键差异。我们的分析表明,约32%的基因在共生状态和致病状态之间存在变异。值得注意的是,我们确定了与肺炎相关的途径和重要毒力因子的变化。此外,通过氨苄西林敏感性试验证实,健康组和肺炎组之间由于PBP3突变导致的β-内酰胺耐药性存在显著差异,其突变模式为D350N、S357N、S385T、L389F。这些发现为NTHi致病性的基因组基础提供了有价值的见解,并可能为更有针对性的临床诊断和治疗提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/867a866ab504/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/73e7d18a600d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/61e7a65722f4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/29bfbe5f1b39/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/4a31ad2b6b1c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/7691dcfb527a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/2ce8f0ca6965/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/867a866ab504/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/73e7d18a600d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/61e7a65722f4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/29bfbe5f1b39/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/4a31ad2b6b1c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/7691dcfb527a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/2ce8f0ca6965/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d757/11625288/867a866ab504/gr6.jpg

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