Mycobacterial Effectors Promoting Tuberculosis Infection

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 7558

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Guest Editor
Université de Lille, CNRS UMR8204, INSERM U1019, CHU Lille, Centre d’Infection et d’Immunité de Lille, Institut Pasteur de Lille, 59000 Lille, France
Interests: tuberculosis; host-pathogen interactions; Mycobacterium; cell wall; protein-protein interactions

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Guest Editor
Université de Lille, CNRS UMR8204, INSERM U1019, CHU Lille, Centre d’Infection et d’Immunité de Lille, Institut Pasteur de Lille, 59000 Lille, France
Interests: tuberculosis; host-pathogen interactions; Mycobacterium; cell signaling; immune response; host directed therapies; macrophages; lung diseases
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Special Issue Information

Dear Colleagues,

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), which is the first leading cause of death around the world due to a single infectious agent. In 2017, TB killed an estimated 1.6 million people, according to the WHO. In addition, there is an alarming increase of multi-resistant drug TB cases. Therefore, understanding the mechanisms leading to the development of the disease is urgently needed to develop efficient strategies against TB.

Mtb is a successful pathogen, which, upon inhalation, is able to infect the host alveolar macrophages. The bacilli is able to prevent the acidification of its containing vacuole by blocking the phagosomal maturation. During its vacuolar lifetime, Mtb is able to survive in this harsh environment by resisting the host immune response and scavenging the nutrients necessary for its survival (like lipids or iron). Ultimately, Mtb can escape the vacuole and reside inside the cell cytoplasm.

Therefore, Mtb has developed a huge set of mechanisms to promote its survival and massively replicate during its prolonged stay in the host. Several virulence factors of Mtb have been identified with the help of genetic tools and animal models. Among the most studied mycobacterial effectors, one can cite the ESX/type VII secretion system substrates (ESAT-6/CFP-10), the eukaryotic-like protein kinase (PknG), as well as several components of the very peculiar mycobacterial cell wall (PDIM, mycolic acids). Nonetheless, many other mechanisms remain to be identified and characterized to gain a better understanding of TB pathogenesis.

For this Special Issue of Pathogens, we kindly invite authors to submit an original research article or a review focusing on the mycobacterial effectors promoting TB infection. Potential topics could include (but are not limited to): host–pathogen interactions, virulence factors of Mtb, intravacuolar and/or intracytoplasmic survival of Mtb, mechanisms of resistance, and interference with host cell signaling.

Dr. Romain Veyron-Churlet
Dr. Arnaud Machelart
Guest Editors

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Keywords

  • tuberculosis
  • infection
  • Mycobacterium
  • host–pathogen interactions
  • virulence factors
  • mechanisms of resistance

Published Papers (2 papers)

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Research

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13 pages, 2281 KiB  
Article
Mycobacterium tuberculosis Rv0341 Promotes Mycobacterium Survival in In Vitro Hostile Environments and within Macrophages and Induces Cytokines Expression
by Abualgasim Elgaili Abdalla, Shuangquan Yan, Jie Zeng, Wanyan Deng, Longxiang Xie and Jianping Xie
Pathogens 2020, 9(6), 454; https://doi.org/10.3390/pathogens9060454 - 8 Jun 2020
Cited by 6 | Viewed by 2584
Abstract
Mycobacterium tuberculosis represents an ancient deadly human pathogen that can survive and multiply within macrophages. The effectors are key players for the successful pathogenesis of this bacterium. M. tuberculosis open reading frame (ORF) Rv0341, a pathogenic mycobacteria-specific gene, was found to be [...] Read more.
Mycobacterium tuberculosis represents an ancient deadly human pathogen that can survive and multiply within macrophages. The effectors are key players for the successful pathogenesis of this bacterium. M. tuberculosis open reading frame (ORF) Rv0341, a pathogenic mycobacteria-specific gene, was found to be upregulated in macrophages isolated from human tuberculosis granuloma and inside the macrophages during in vitro infection by M. tuberculosis. To understand the exact role of this gene, we expressed the Rv0341 gene in M. smegmatis, which is a non-pathogenic Mycobacterium. We found that Rv0341 expression can alter colony morphology, reduce the sliding capability, and decrease the cell wall permeability of M. smegmatis. Furthermore, Rv0341 remarkably enhanced M. smegmatis survival within macrophages and under multiple in vitro stress conditions when compared with the control strain. Ms_Rv0341 significantly induced expression of TNF-α, IL-1β, and IL-10 compared with M. smegmatis harboring an empty vector. In summary, these data suggest that Rv0341 is one of the M. tuberculosis virulence determinants that can promote bacilli survival in harsh conditions and inside macrophages. Full article
(This article belongs to the Special Issue Mycobacterial Effectors Promoting Tuberculosis Infection)
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Review

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15 pages, 1689 KiB  
Review
In Vivo Methods to Study Protein–Protein Interactions as Key Players in Mycobacterium Tuberculosis Virulence
by Romain Veyron-Churlet and Camille Locht
Pathogens 2019, 8(4), 173; https://doi.org/10.3390/pathogens8040173 - 1 Oct 2019
Cited by 5 | Viewed by 4492
Abstract
Studies on protein–protein interactions (PPI) can be helpful for the annotation of unknown protein functions and for the understanding of cellular processes, such as specific virulence mechanisms developed by bacterial pathogens. In that context, several methods have been extensively used in recent years [...] Read more.
Studies on protein–protein interactions (PPI) can be helpful for the annotation of unknown protein functions and for the understanding of cellular processes, such as specific virulence mechanisms developed by bacterial pathogens. In that context, several methods have been extensively used in recent years for the characterization of Mycobacterium tuberculosis PPI to further decipher tuberculosis (TB) pathogenesis. This review aims at compiling the most striking results based on in vivo methods (yeast and bacterial two-hybrid systems, protein complementation assays) for the specific study of PPI in mycobacteria. Moreover, newly developed methods, such as in-cell native mass resonance and proximity-dependent biotinylation identification, will have a deep impact on future mycobacterial research, as they are able to perform dynamic (transient interactions) and integrative (multiprotein complexes) analyses. Full article
(This article belongs to the Special Issue Mycobacterial Effectors Promoting Tuberculosis Infection)
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