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一种能够导致抑菌性生长停滞的淋球菌HicAB毒素-抗毒素系统的特性

The Characterization of a Gonococcal HicAB Toxin-Antitoxin System Capable of Causing Bacteriostatic Growth Arrest.

作者信息

Bagabas Salwa S, Trujillo-Mendoza Jorge, Stocks Michael J, Turner David P J, Oldfield Neil J

机构信息

Department of Biological Sciences, Faculty of Science, University of Jeddah, Jeddah 23445, Saudi Arabia.

School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.

出版信息

Microorganisms. 2025 Jul 9;13(7):1619. doi: 10.3390/microorganisms13071619.

DOI:10.3390/microorganisms13071619
PMID:40732128
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12297915/
Abstract

is the causative agent of the sexually transmitted infection gonorrhea. Preventative vaccines or novel treatments based on a better understanding of the molecular basis of infection are required as resistance to current antibiotics is widespread. Toxin-antitoxin (TA) systems modulate bacterial physiology by interfering with vital cellular processes; type II TA systems, where both toxin and antitoxin are proteins, are the best-studied. Bioinformatics analysis revealed genes encoding an uncharacterized type II HicAB TA system in the strain FA1090 chromosome, which were also present in >83% of the other gonococcal genome sequences examined. Gonococcal HicA overproduction inhibited bacterial growth in an effect that could be counteracted by the co-expression of HicB. Kill/rescue assays showed that this effect was bacteriostatic rather than bactericidal. The site-directed mutagenesis of key histidine and glycine residues (Gly22, His24, His29) abolished HicA-mediated growth arrest. FA1090∆ and complemented derivatives that expressed IPTG-inducible , , or , respectively, grew as wild type, except for IPTG-induced FA1090∆ RT-PCR demonstrated that are transcribed in vitro under the culture conditions used. The deletion of had no effect on biofilm formation. Our study describes the first characterization of a HicAB TA system in .

摘要

是性传播感染淋病的病原体。由于对当前抗生素的耐药性广泛存在,因此需要基于对感染分子基础的更好理解来开发预防性疫苗或新型治疗方法。毒素-抗毒素(TA)系统通过干扰重要的细胞过程来调节细菌生理;II型TA系统中,毒素和抗毒素都是蛋白质,是研究得最为透彻的。生物信息学分析揭示,在菌株FA1090染色体中存在编码一种未表征的II型HicAB TA系统的基因,在所检测的其他淋球菌基因组序列中,超过83%也存在这些基因。淋球菌HicA的过量表达抑制了细菌生长,这种效应可通过共表达HicB来抵消。杀伤/拯救试验表明,这种效应是抑菌性而非杀菌性的。关键组氨酸和甘氨酸残基(Gly22、His24、His29)的定点诱变消除了HicA介导的生长停滞。分别表达IPTG诱导型、或的FA1090∆及互补衍生物,除IPTG诱导的FA1090∆外,均如野生型一样生长。RT-PCR表明,在所使用的培养条件下,在体外转录。的缺失对生物膜形成没有影响。我们的研究首次描述了淋球菌中HicAB TA系统的特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/0c9e83a3df45/microorganisms-13-01619-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/8709a0ce802c/microorganisms-13-01619-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/05c51ffe3acd/microorganisms-13-01619-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/23dd48f81bf5/microorganisms-13-01619-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/6e2011de471f/microorganisms-13-01619-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/68de9d85a331/microorganisms-13-01619-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/0c9e83a3df45/microorganisms-13-01619-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/8709a0ce802c/microorganisms-13-01619-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/05c51ffe3acd/microorganisms-13-01619-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/23dd48f81bf5/microorganisms-13-01619-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/6e2011de471f/microorganisms-13-01619-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/68de9d85a331/microorganisms-13-01619-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/922d/12297915/0c9e83a3df45/microorganisms-13-01619-g006.jpg

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Nat Microbiol. 2025 Apr;10(4):939-957. doi: 10.1038/s41564-025-01968-y. Epub 2025 Apr 2.
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