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一种移动辅助基因组的 VirB4 ATP 酶协调 TBCF10839 的核心基因组编码的生理、代谢和毒力特征。

A VirB4 ATPase of the mobile accessory genome orchestrates core genome-encoded features of physiology, metabolism, and virulence of TBCF10839.

机构信息

Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.

Research Core Unit Genomics, Hannover Medical School, Hannover, Germany.

出版信息

Front Cell Infect Microbiol. 2023 Jul 27;13:1234420. doi: 10.3389/fcimb.2023.1234420. eCollection 2023.

DOI:10.3389/fcimb.2023.1234420
PMID:37577372
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10413270/
Abstract

TBCF10839 is a highly virulent strain that can persist and replicate in human neutrophils. Screening of a signature-tagged mutagenesis (STM) TBCF10839 transposon library in phagocytosis tests identified a mutant that carried the transposon in the VirB4 homolog 5PG21 of an integrative and conjugative element (ICE)-associated type IV secretion system of the pKLC102 subtype. 5P21 TBCF10839 insertion mutants were deficient in metabolic versatility, secretion, quorum sensing, and virulence. The mutants were efficiently killed in phagocytosis tests and were avirulent in an acute murine airway infection model . The inactivation of 5PG21 silenced the , , and operons and the gene expression for the synthesis of hydrogen cyanide, the antimetabolite l-2-amino-4-methoxy--3-butenoic acid, and the H2- and H3-type VI secretion systems and their associated effectors. The mutants were impaired in the utilization of carbon sources and stored compounds that are not funneled into intermediary metabolism. This showcase demonstrates that a single gene of the mobile accessory genome can become an essential element to operate the core genome-encoded features of metabolism and virulence.

摘要

TBCF10839 是一种高毒力的菌株，能够在人中性粒细胞中持续复制。在吞噬作用试验中对标记突变体筛选（STM）TBCF10839 转座子文库进行筛选，发现一个携带转座子的突变体，该转座子位于整合和共轭元件（ICE）相关的 IV 型分泌系统 pKLC102 亚类的 VirB4 同源物 5PG21 中。5P21 TBCF10839 插入突变体在代谢多样性、分泌、群体感应和毒力方面存在缺陷。在吞噬作用试验中，突变体被有效杀死，并且在急性小鼠气道感染模型中无致病性。5PG21 的失活沉默了 、 、 和 操纵子以及合成氰化氢、代谢拮抗物 l-2-氨基-4-甲氧基-3-丁烯酸以及 H2 和 H3 型 VI 型分泌系统及其相关效应物的基因表达。突变体在利用碳源和储存化合物方面存在缺陷，这些化合物不会流入中间代谢。该实例展示了移动辅助基因组中的单个基因可以成为操作核心基因组编码的代谢和毒力特征的必需元素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/a5c0db48ffef/fcimb-13-1234420-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/6ef5ce62c786/fcimb-13-1234420-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/36f7c13c2727/fcimb-13-1234420-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/3fb45268c847/fcimb-13-1234420-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/abb4b904e3c0/fcimb-13-1234420-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/2cce92454a50/fcimb-13-1234420-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/dfb111794473/fcimb-13-1234420-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/49ab0e70ef6b/fcimb-13-1234420-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/a5c0db48ffef/fcimb-13-1234420-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/6ef5ce62c786/fcimb-13-1234420-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/36f7c13c2727/fcimb-13-1234420-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/3fb45268c847/fcimb-13-1234420-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/abb4b904e3c0/fcimb-13-1234420-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/2cce92454a50/fcimb-13-1234420-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/dfb111794473/fcimb-13-1234420-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/49ab0e70ef6b/fcimb-13-1234420-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff87/10413270/a5c0db48ffef/fcimb-13-1234420-g008.jpg

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