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A novel protease inhibitor causes inclusion vacuole reduction and disrupts the intracellular growth of Chlamydia trachomatis.

Abstract：

:Chlamydia (C.) trachomatis, characterized by a unique biphasic life cycle, is an obligate intracellular bacterial pathogen which is responsible for the highest number of sexually transmitted bacterial infections globally. However, its pathogenic mechanisms have not been fully elucidated because of its unique developmental cycle and obligate intracellular nature. High temperature requirement (HtrA), a critical protease and chaperone, has been previously demonstrated to be essential for several functions and the replicative phase in the C. trachomatis developmental cycle. In the current study, we designed and synthesized a novel peptidomimetic inhibitor targeting C. trachomatis HtrA (CtHtrA) using homology modeling and chemical synthesis. The inhibitor was tested in chlamydia in the mid-replicative phase and resulted in a significant loss of viable infectious progeny and diminishing inclusion size and number at a relatively low concentration. This finding not only indicates that CtHtrA plays a critical role during the replicative phase of the chlamydial developmental cycle but also reveals a useful target for the design of novel anti-chlamydial agents.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Zhou Y,Lu X,Huang D,Lu Y,Zhang H,Zhang L,Yu P,Wang F,Wang Y

doi

10.1016/j.bbrc.2019.05.184

subject

Has Abstract

pub_date

2019-08-13 00:00:00

pages

157-162

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)31102-7

journal_volume

516

pub_type

杂志文章

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