microRNAs associated with the pathogenesis and their role in regulating various signaling pathways during Mycobacterium tuberculosis infection

Abstract

Despite more than a decade of active study, tuberculosis (TB) remains a serious health concern across the world, and it is still the biggest cause of mortality in the human population. Pathogenic bacteria recognize host-induced responses and adapt to those hostile circumstances. This high level of adaptability necessitates a strong regulation of bacterial metabolic characteristics. Furthermore, the immune reponse of the host virulence factors such as host invasion, colonization, and survival must be properly coordinated by the pathogen. This can only be accomplished by close synchronization of gene expression. Understanding the molecular characteristics of mycobacterial pathogenesis in order to discover therapies that prevent or resolve illness relies on the bacterial capacity to adjust its metabolism and replication in response to various environmental cues as necessary. An extensive literature details the transcriptional alterations of host in response to in vitro environmental stressors, macrophage infection, and human illness. Various studies have recently revealed the finding of several microRNAs (miRNAs) that are believed to play an important role in the regulatory networks responsible for adaptability and virulence in Mycobacterium tuberculosis. We highlighted the growing data on the existence and quantity of several forms of miRNAs in the pathogenesis of M. tuberculosis, considered their possible relevance to disease etiology, and discussed how the miRNA-based signaling pathways regulate bacterial virulence factors.

In silico analysis of miRNA target genes possibly induced by tuberculosis infection

“…El miRNA 146b ha sido asociado a la regulación de diversas vías de señalización y algunos de sus genes blanco descritos son AKT3, IL6, IRAK1, NFKB1, TLR4 (15) ; y se ha reportado que se sobre expresa en el suero de pacientes con TB activa (16) . El miR-155 modula la producción de mediadores inflamatorios en respuesta a estímulos microbianos regulando negativamente la expresión de TAK1 y la proteína de unión a TRAF6.…”

“…El miR-155 modula la producción de mediadores inflamatorios en respuesta a estímulos microbianos regulando negativamente la expresión de TAK1 y la proteína de unión a TRAF6. También se ha observado que, en la infección por TB, miR-155 se sobre expresa e inhibe la autofagia inducida por IFN-γ; algunos de los genes blanco a los que ha sido asociado son AKT1, APAF1, ATP6V1H, CASP3 (15) . Interesantemente, miR-155 tiene doble función durante la infección con TB; por un lado, mantiene la supervivencia de los macrófagos infectados con Mtb y, por otro lado, promueve la supervivencia y la función de las células T específicas de Mtb (17) .…”

Analysis of the noncoding RNA regulatory networks of H37Rv- and H37Rv△1759c-infected macrophages

“…The increased expression of circAGFG1 in alveolar lavage fluid of ATB patients can inhibit the apoptosis of M. tb-infected macrophages and promote autophagy through the circAGFG1/miR-1257/Notch2 axis ( Shi et al, 2020 ). NcRNAs also have the potential to serve as diagnostic markers, therapeutic targets or therapeutic evaluation indicators for TB ( Davuluri and Chauhan, 2022 ; Hemati et al, 2022 ; Liang et al, 2022 ; Wang L. et al, 2022 ; Wang Q. et al, 2022 ; Zhang et al, 2022 ). Studies found that the upregulated hsa_circ_0001953, hsa_circ_0009024, hsa_circ_051239, hsa_circ_029965 and hsa_circ_404022 and the downregulated hsa_circ_0001380 and hsa_circRNA_103571 in the serum and the downregulated NONHSAT101518.2, NONHSAT067134.2, NONHSAT148822.1, and NONHSAT078957.2 in serum exosomes could be used as potential biomarkers for patients with ATB disease ( Huang et al, 2018 ; Yi et al, 2018 ; Luo et al, 2020 ; Fang et al, 2021 ).…”

Oral Spirochete Treponema denticola Intraoral Infection Reveals Unique miR-133a, miR-486, miR-126-3p, miR-126-5p miRNA Expression Kinetics during Periodontitis

“…Each specific miRNA can have hundreds of different targets that affect entire gene expression networks [3]. miRNAs have been implicated in many diseases, and regulate the immune response of hosts infected with bacteria such as Treponema pallidum [4], Helicobacter pylori [5], Mycobacterium avium [6], M. tuberculosis [7], Salmonella [8], and Listeria monocytogenes [9]. Hence, understanding the expression pattern of miRNAs could potentially lead to the development of novel diagnostic biomarkers for various complicated microbial infectiondriven inflammatory diseases, including periodontal disease (PD).…”