An in Silico Analysis of RpoB Mutations to Affect Chlamydia Trachomatis Sensitivity to Rifamycin

Overview

Journal J Genet Eng Biotechnol

Specialty Biotechnology

Date 2022 Oct 25

PMID 36282371

Authors

Ichrak Benamri

Maryame Azzouzi

Ahmed Moussa

Fouzia Radouani

Affiliations

Soon will be listed here.

Abstract

Background: Chlamydia trachomatis is an obligate intracellular gram-negative pathogen, responsible for diverse affections, mainly trachoma and sexually transmitted diseases. Antibiotics are the commonly used drugs to tackle chlamydiae infections. However, when overused or wrongly used this may lead to strains' resistance to antibiotics, this phenomenon represents a real health problem worldwide. Numerous studies showed the association of Chlamydia trachomatis resistance with mutations in different genes; these mutations could have a deleterious or neutral impacts on the encoded proteins. The aim of this study is to perform an in silico analysis of C. trachomatis rpoB-encoded proteins using numerous bioinformatics tools and to identify the functional and structural-related effects of the mutations and consequently their impact on the bacteria sensitivity to antibiotics.

Results: The analysis revealed that the prediction of the damaging impact related to the mutations in rpoB-encoded proteins showed eight mutations: V136F, Q458K, V466A, A467T, H471N, H471Y, H471L, and I517M with big deleterious effects. Among them, six mutations, V136F, Q458K, V466A, A467T, H471N, and I517M, are located in a highly conserved regions decreasing the protein's stability. Furthermore, the structures analysis showed that the mutations A467T, H471N, I517M, and V136F models had a high deviation compared to the wild type. Moreover, the prediction of protein-protein network indicated that rpoB wild type interacts strongly with 10 proteins of C. trachomatis, which are playing different roles at different levels.

Conclusion: As conclusion, the present study revealed that the changes observed in the encoded proteins can affect their functions and structures, in addition to their interactions with other proteins which impact the bacteria sensitivity to antibiotics. Consequently, the information revealed through this in silico analysis would be useful for deeper exploration to understand the mechanisms of C. trachomatis resistance and enable managing the infection to avoid its complications. We recommend further investigations and perform deeper experimental analysis with collaboration between bioinformaticians, physicians, biologists, pharmacists, and chemistry and biochemistry scientists.

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