A novel protease inhibitor causes inclusion vacuole reduction and disrupts the intracellular growth of Chlamydia trachomatis.
Biochem Biophys Res Commun
; 516(1): 157-162, 2019 08 13.
Article
em En
| MEDLINE
| ID: mdl-31202460
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
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Vacúolos
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Infecções por Chlamydia
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Chlamydia trachomatis
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Peptidomiméticos
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Antibacterianos
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article