Special Issue "Virulence Studies of Pathogenic Mycobacteria of Humans and Animal"

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: 20 May 2019

Special Issue Editors

Guest Editor
Prof. Frederick D. Quinn

Department of Infectious Diseases, University of Georgia, Athens, GA, USA
Website | E-Mail
Interests: tuberculosis; animal models; virulence factors; vaccines
Guest Editor
Dr. Kaori Sakamoto

Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
Website | E-Mail
Interests: tuberculosis, pathology, macrophage, scavenger receptors, veterinary

Special Issue Information

Dear Colleagues,

Mycobacterium tuberculosis is the number one, bacterial cause of human deaths worldwide. Currently available vaccines are effective mainly against childhood tuberculosis, and treatment requires months of multiple antibiotics, which have serious side effects. Despite numerous ongoing vaccine and antibiotic clinical trials, the field is outpaced by the development of antibiotic resistance and vaccine trial failures, and we are no closer to eliminating the disease than we were 20 years ago. Mycobacterial species also infect and cause disease in most other vertebrate species, with the potential for zoonotic transmission. A better understanding of how mycobacteria cause disease, and thwart vaccine and antibiotic efforts, is needed in order to achieve elimination. In this special issue, we invite you to submit a review or original research article related to virulence factors and mechanisms contributing to mycobacterial infection in humans and animals.

Prof. Frederick D. Quinn
Dr. Kaori Sakamoto
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mycobacterium
  • animal models
  • diagnosis
  • pathology
  • veterinary
  • virulence

Published Papers (5 papers)

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Research

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Open AccessCommunication Mycobacterium smegmatis But Not Mycobacterium avium subsp. hominissuis Causes Increased Expression of the Long Non-Coding RNA MEG3 in THP-1-Derived Human Macrophages and Associated Decrease of TGF-β
Microorganisms 2019, 7(3), 63; https://doi.org/10.3390/microorganisms7030063
Received: 30 January 2019 / Revised: 13 February 2019 / Accepted: 26 February 2019 / Published: 27 February 2019
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Abstract
Pathogenic mycobacteria are able to persist intracellularly in macrophages, whereas non-pathogenic mycobacteria are effectively combated and eliminated after their phagocytosis. It is known that TGF-β plays an important role in this context. Infection with pathogenic mycobacteria such as Mycobacterium tuberculosis or M. avium [...] Read more.
Pathogenic mycobacteria are able to persist intracellularly in macrophages, whereas non-pathogenic mycobacteria are effectively combated and eliminated after their phagocytosis. It is known that TGF-β plays an important role in this context. Infection with pathogenic mycobacteria such as Mycobacterium tuberculosis or M. avium leads to production of active TGF-β, which blocks the ability of IFN-γ and TNF-α to inhibit intracellular replication. On the other hand, it is known that the long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) is involved in the regulation of TGF-β. In this study, we show how the infection of THP-1-derived human macrophages with the saprophytic M. smegmatis but not with the facultatively pathogenic M. avium subsp. hominissuis leads to increased MEG3 expression. This is associated with the downregulation of DNA methyltransferases (DNMT) 1 and 3b, which are known to regulate MEG3 expression via promoter hypermethylation. Consequently, we observe a significant downregulation of TGF-β in M. smegmatis-infected macrophages but not in M. avium subsp. hominissuis pointing to lncRNAs as novel mediators of host cell response during mycobacterial infections. Full article
(This article belongs to the Special Issue Virulence Studies of Pathogenic Mycobacteria of Humans and Animal)
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Open AccessArticle Optimization of In Vitro Mycobacterium avium and Mycobacterium intracellulare Growth Assays for Therapeutic Development
Microorganisms 2019, 7(2), 42; https://doi.org/10.3390/microorganisms7020042
Received: 17 December 2018 / Revised: 12 January 2019 / Accepted: 20 January 2019 / Published: 1 February 2019
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Abstract
Infection with nontuberculous mycobacteria (NTM) is a complication of lung disease in immunocompromised patients, including those with human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). The most widespread, disease-causing NTM is Mycobacterium avium [...] Read more.
Infection with nontuberculous mycobacteria (NTM) is a complication of lung disease in immunocompromised patients, including those with human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). The most widespread, disease-causing NTM is Mycobacterium avium complex (MAC), which colonizes the lungs as a combination of Mycobacterium avium, Mycobacterium intracellulare, and other mycobacterial species. While combination drug therapy exists for MAC colonization, there is no cure. Therapeutic development to treat MAC has been difficult because of the slow-growing nature of the bacterial complex, limiting the ability to characterize the bacteria’s growth in response to new therapeutics. The development of a technology that allows observation of both the MAC predominant strains and MAC could provide a means to develop new therapeutics to treat NTM. We have developed a new methodology in which M. avium and M. intracellulare can be optimally grown in short term culture to study each strain independently and in combination, as a monitor of growth kinetics and efficient therapeutic testing protocols. Full article
(This article belongs to the Special Issue Virulence Studies of Pathogenic Mycobacteria of Humans and Animal)
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Open AccessArticle Membrane and Cytoplasmic Proteins of Mycobacterium avium subspecies paratuberculosis that Bind to Novel Monoclonal Antibodies
Microorganisms 2018, 6(4), 127; https://doi.org/10.3390/microorganisms6040127
Received: 22 October 2018 / Revised: 29 November 2018 / Accepted: 8 December 2018 / Published: 11 December 2018
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Abstract
Monoclonal antibodies against Mycobacterium avium subspecies paratuberculosis (Map) proteins are important tools in Johne’s disease research and diagnostics. Johne’s disease is a chronic inflammatory intestinal disease of cattle, sheep, and other ruminant animals. We have previously generated multiple sets of monoclonal antibodies (mAbs) [...] Read more.
Monoclonal antibodies against Mycobacterium avium subspecies paratuberculosis (Map) proteins are important tools in Johne’s disease research and diagnostics. Johne’s disease is a chronic inflammatory intestinal disease of cattle, sheep, and other ruminant animals. We have previously generated multiple sets of monoclonal antibodies (mAbs) in different studies; however, because many were generated and screened against a whole-cell extract of Map, the antigens that bind to these antibodies remained unknown. In this study, we used three different approaches to identify the corresponding Map antigens for 14 mAbs that could not be identified previously. In the first approach, a new Map-lambda phage expression library was screened to identify corresponding antigens for 11 mAbs. This approach revealed that mAbs 7C8, 9H3, 12E4, 3G5, and 11B8 all detect MAP_3404 encoding the biotin carboxylase subunit of acetyl-CoA carboxylase, while mAbs 7A6, 11F8, and 10C12 detect the GroEL2 chaperonin (MAP_3936), 6C9 detects electron transfer flavoprotein (MAP_3060c), and 14G11 detects MAP_3976, a lipoprotein anchoring transpeptidase. The epitopes to a selection of these mAbs were also defined. In a second approach, MAP_2698c bound monoclonal antibody (mAb) 14D4 as determined using protein arrays. When both of these approaches failed to identify the antigen for mAb 12C9, immunoprecipitation, mass spectrometry analysis, and codon optimization was used to identify the membrane protein, MAP_4145, as the reacting antigen. Characterized antibodies were used to quickly interrogate mycobacterial proteomic preps. We conclude by providing a complete catalog of available mAbs to Map proteins, along with their cognate antigens and epitopes, if known. These antibodies are now thoroughly characterized and more useful for research and diagnostic purposes. Full article
(This article belongs to the Special Issue Virulence Studies of Pathogenic Mycobacteria of Humans and Animal)
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Review

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Open AccessReview Mycobacterium abscessus: Environmental Bacterium Turned Clinical Nightmare
Microorganisms 2019, 7(3), 90; https://doi.org/10.3390/microorganisms7030090
Received: 27 January 2019 / Revised: 15 March 2019 / Accepted: 19 March 2019 / Published: 22 March 2019
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Abstract
Mycobacteria are a large family of over 100 species, most of which do not cause diseases in humans. The majority of the mycobacterial species are referred to as nontuberculous mycobacteria (NTM), meaning they are not the causative agent of tuberculous (TB) or leprosy, [...] Read more.
Mycobacteria are a large family of over 100 species, most of which do not cause diseases in humans. The majority of the mycobacterial species are referred to as nontuberculous mycobacteria (NTM), meaning they are not the causative agent of tuberculous (TB) or leprosy, i.e., Mycobacterium tuberculous complex and Mycobacterium leprae, respectively. The latter group is undoubtedly the most infamous, with TB infecting an estimated 10 million people and causing over 1.2 million deaths in 2017 alone TB and leprosy also differ from NTM in that they are only transmitted from person to person and have no environmental reservoir, whereas NTM infections are commonly acquired from the environment. It took until the 1950′s for NTM to be recognised as a potential lung pathogen in people with underlying pulmonary disease and another three decades for NTM to be widely regarded by the medical community when Mycobacterium avium complex was identified as the most common group of opportunistic pathogens in AIDS patients. This review focuses on an emerging NTM called Mycobacterium abscessus (M. abs). M. abs is a rapidly growing NTM that is responsible for opportunistic pulmonary infections in patients with structural lung disorders such as cystic fibrosis and bronchiectasis, as well as a wide range of skin and soft tissue infections in humans. In this review, we discuss how we came to understand the pathogen, how it is currently treated and examine drug resistance mechanisms and novel treatments currently in development. We highlight the urgent need for new and effective treatments for M. abs infection as well as improved in vivo methods of efficacy testing. Full article
(This article belongs to the Special Issue Virulence Studies of Pathogenic Mycobacteria of Humans and Animal)
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Open AccessReview MmpL Proteins in Physiology and Pathogenesis of M. tuberculosis
Microorganisms 2019, 7(3), 70; https://doi.org/10.3390/microorganisms7030070
Received: 15 January 2019 / Revised: 14 February 2019 / Accepted: 3 March 2019 / Published: 5 March 2019
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Abstract
Mycobacterium tuberculosis (Mtb) remains an important human pathogen. The Mtb cell envelope is a critical bacterial structure that contributes to virulence and pathogenicity. Mycobacterial membrane protein large (MmpL) proteins export bulky, hydrophobic substrates that are essential for the unique structure of [...] Read more.
Mycobacterium tuberculosis (Mtb) remains an important human pathogen. The Mtb cell envelope is a critical bacterial structure that contributes to virulence and pathogenicity. Mycobacterial membrane protein large (MmpL) proteins export bulky, hydrophobic substrates that are essential for the unique structure of the cell envelope and directly support the ability of Mtb to infect and persist in the host. This review summarizes recent investigations that have enabled insight into the molecular mechanisms underlying MmpL substrate export and the role that these substrates play during Mtb infection. Full article
(This article belongs to the Special Issue Virulence Studies of Pathogenic Mycobacteria of Humans and Animal)
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