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Microorganisms
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Mycobacterium abscessus: Current Knowledgement on an Emerging Pathogen
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Mycobacterium abscessus: Current Knowledgement on an Emerging Pathogen

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

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 6982

Special Issue Editor

Dr. Laura Rindi

E-Mail Website
Guest Editor
Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Via San Zeno, 35/39, 56127 Pisa, Italy
Interests: Mycobacterium tuberculosis; non-tuberculous mycobacteria; antimicrobila resistance in mycobacteria

Special Issue Information

Dear Colleagues,

The Special Issue entitled " Mycobacterium Abscessus: Current Knowledgement on an Emerging Pathogen" aims to present recent research on any aspect of Mycobacterium abscessus. M. abscessus is a rapidly growing mycobacterium associated with several diseases in humans, of which lung disease is the most common, particularly in patients with underlying lung disease such as bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis; it is the second most common cause of nontuberculous mycobacteria pulmonary disease in many countries after Mycobacterium avium complex. Infections caused by M. abscessus are often difficult to treat since therapy, which needs the use of a combination drug regimen, is long, expensive, more toxic and more likely to fail than tuberculosis therapy. The current Special Issue aims to highlight the latest scientific findings on this pathogen. Some of its focal points include, but are not limited to, the following:

1. Infection and pathogenesis.
2. Recent advancements in diagnosis.
3. Mechanisms of drug resistance.
4. Novel treatment strategies.

Reviews, original research, and communications will be welcome. 

Dr. Laura Rindi
Guest Editor

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 submissions that pass pre-check are 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 2700 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.

Published Papers (5 papers)

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Research

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11 pages, 3287 KiB  
Article
Exploring the Role of a Putative Secondary Metabolite Biosynthesis Pathway in Mycobacterium abscessus Pathogenesis Using a Xenopus laevis Tadpole Model
by Nicholas James Miller, Dionysia Dimitrakopoulou, Laurel A. Baglia, Martin S. Pavelka, Jr. and Jacques Robert
Microorganisms 2024, 12(6), 1120; https://doi.org/10.3390/microorganisms12061120 - 31 May 2024
Viewed by 448
Abstract
Mycobacterium abscessus (Mab) is an emerging human pathogen that has a high rate of incidence in immunocompromised individuals. We have found a putative secondary metabolite pathway within Mab, which may be a key factor in its pathogenesis. This novel pathway is encoded [...] Read more.
Mycobacterium abscessus (Mab) is an emerging human pathogen that has a high rate of incidence in immunocompromised individuals. We have found a putative secondary metabolite pathway within Mab, which may be a key factor in its pathogenesis. This novel pathway is encoded in a gene cluster spanning MAB_0284c to 0305 and is related to Streptomyces pathways, producing the secondary metabolites streptonigrin and nybomycin. We constructed an in-frame deletion of the MAB_0295 (phzC) gene and tested it in our Xenopus laevis animal model. We have previously shown that X. laevis tadpoles, which have functional lungs and T cells, can serve as a reliable comparative model for persistent Mab infection and pathogenesis. Here, we report that tadpoles intraperitoneally infected with the ∆phzC mutant exhibit early decreased bacterial loads and significantly increased survival compared with those infected with WT Mab. ∆phzC mutant Mab also induced lower transcript levels of several pro-inflammatory cytokines (IL-1β, TNF-α, iNOS, IFN-γ) than those of WT Mab in the liver and lungs. In addition, there was impaired macrophage recruitment and decreased macrophage infection in tadpoles infected with the ∆phzC mutant, by tail wound inoculation, compared to those infected with the WT bacteria, as assayed by intravital confocal microscopy. These data underline the relevance and usefulness of X. laevis tadpoles as a novel comparative animal model to identify genetic determinants of Mab immunopathogenesis, suggesting a role for this novel and uncharacterized pathway in Mab pathogenesis and macrophage recruitment. Full article
(This article belongs to the Special Issue Mycobacterium abscessus: Current Knowledgement on an Emerging Pathogen)
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19 pages, 2136 KiB  
Article
Predominantly Orphan Secretome in the Lung Pathogen Mycobacterium abscessus Revealed by a Multipronged Growth-Phase-Driven Strategy
by Harish Chandra, Manish K. Gupta, Ying-Wai Lam and Jagjit S. Yadav
Microorganisms 2024, 12(2), 378; https://doi.org/10.3390/microorganisms12020378 - 12 Feb 2024
Viewed by 980
Abstract
The emerging lung pathogen Mycobacterium abscessus is understudied for its virulence determinants and molecular targets for diagnosis and therapeutics. Here, we report a comprehensive secretome (600 proteins) of this species, which was identified using a multipronged strategy based on genetic/genomic, proteomic, and bioinformatic [...] Read more.
The emerging lung pathogen Mycobacterium abscessus is understudied for its virulence determinants and molecular targets for diagnosis and therapeutics. Here, we report a comprehensive secretome (600 proteins) of this species, which was identified using a multipronged strategy based on genetic/genomic, proteomic, and bioinformatic approaches. In-solution digested bottom-up proteomics from various growth phases identified a total of 517 proteins, while 2D-GE proteomics identified 33 proteins. A reporter-gene-fusion-based genomic library that was custom-generated in this study enabled the detection of 23 secretory proteins. A genome-wide survey for N-terminal signal sequences using bioinformatic tools (Psortb 2.0 and SignalP 3.0) combined with a strategy of the subtraction of lipoproteins and proteins containing multiple transmembrane domains yielded 116 secretory proteins. A homology search against the M. tuberculosis database identified nine additional secretory protein homologs that lacked a secretory signal sequence. Considering the little overlap (80 proteins) among the different approaches used, this study emphasized the importance of using a multipronged strategy for a comprehensive understanding of the secretome. Notably, the majority of the secreted proteins identified (over 50%) turned out to be “orphans” (those with no known functional homologs). The revelation of these species-specific orphan proteins offers a hitherto unexplored repertoire of potential targets for diagnostic, therapeutic, and vaccine research in this emerging lung pathogen. Full article
(This article belongs to the Special Issue Mycobacterium abscessus: Current Knowledgement on an Emerging Pathogen)
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11 pages, 1472 KiB  
Article
Investigating Novel IspE Inhibitors of the MEP Pathway in Mycobacterium
by Seoung-Ryoung Choi and Prabagaran Narayanasamy
Microorganisms 2024, 12(1), 18; https://doi.org/10.3390/microorganisms12010018 - 21 Dec 2023
Viewed by 903
Abstract
In a recent effort to mitigate harm from human pathogens, many biosynthetic pathways have been extensively evaluated for their ability to inhibit pathogen growth and to determine drug targets. One of the important products/targets of such pathways is isopentenyl diphosphate. Isopentenyl diphosphate is [...] Read more.
In a recent effort to mitigate harm from human pathogens, many biosynthetic pathways have been extensively evaluated for their ability to inhibit pathogen growth and to determine drug targets. One of the important products/targets of such pathways is isopentenyl diphosphate. Isopentenyl diphosphate is the universal precursor of isoprenoids, which are essential for the normal functioning of microorganisms. In general, two biosynthetic pathways lead to the formation of isopentenyl diphosphate: (1) the mevalonate pathway in animals; and (2) the non-mevalonate or methylerythritol phosphate (MEP) in many bacteria, and some protozoa and plants. Because the MEP pathway is not found in mammalian cells, it is considered an attractive target for the development of antimicrobials against a variety of human pathogens, including Mycobacterium tuberculosis (M.tb). In the MEP pathway, 4-diphosphocytidyl-2-c-methyl-d-erythritol kinase (IspE) phosphorylates 4-diphosphocytidyl-2-C-methyl-D-erythritol (CDPME) to form 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDPME2P). A virtual high-throughput screening against 15 million compounds was carried out by docking IspE protein. We identified an active heterotricyclic compound which showed enzymatic activity; namely, IC50 of 6 µg/mL against M.tb IspE and a MIC of 12 µg/mL against M.tb (H37Rv). Hence, we designed and synthesized similar new heterotricyclic compounds and tested them against mycobacterium, observing a MIC of 5 µg/mL against M. avium. This study will provide the critical insight necessary for developing novel antimicrobials that target the MEP pathways in pathogens. Full article
(This article belongs to the Special Issue Mycobacterium abscessus: Current Knowledgement on an Emerging Pathogen)
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Review

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12 pages, 420 KiB  
Review
Therapy of Mycobacterium abscessus Infections in Solid Organ Transplant Patients
by Lubna Osman, Christopher Lopez, Yoichiro Natori, Shweta Anjan, Julia Bini Viotti and Jacques Simkins
Microorganisms 2024, 12(3), 596; https://doi.org/10.3390/microorganisms12030596 - 16 Mar 2024
Viewed by 1005
Abstract
Mycobacterium abscessus complex (MABC), a rapidly growing Mycobacterium, is one of the most common causes of non-tuberculous mycobacteria (NTM) infections in the United States of America, and it has been associated with a wide spectrum of infections in immunocompetent and immunosuppressed individuals. [...] Read more.
Mycobacterium abscessus complex (MABC), a rapidly growing Mycobacterium, is one of the most common causes of non-tuberculous mycobacteria (NTM) infections in the United States of America, and it has been associated with a wide spectrum of infections in immunocompetent and immunosuppressed individuals. Eradicating MABC is very challenging, even with prolonged combination therapies. The management of MABC infections in solid organ transplant (SOT) patients is usually complex given their net state of immunosuppression, associated comorbidities, and potential drug–drug interactions, among other things. In this manuscript, we discussed the antimicrobial management of pulmonary and extrapulmonary MABC infections. In addition, we reviewed promising novel therapies such as clofazimine, omadacycline, bedaquiline, and inhaled tigecycline that could join the existing antimicrobial armamentarium to fight this infection associated with significant morbidity and mortality. However, further studies are needed, especially among the immunocompromised host. Full article
(This article belongs to the Special Issue Mycobacterium abscessus: Current Knowledgement on an Emerging Pathogen)
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18 pages, 2476 KiB  
Review
Updated Review on the Mechanisms of Pathogenicity in Mycobacterium abscessus, a Rapidly Growing Emerging Pathogen
by Paula López-Roa, Jaime Esteban and María-Carmen Muñoz-Egea
Microorganisms 2023, 11(1), 90; https://doi.org/10.3390/microorganisms11010090 - 29 Dec 2022
Cited by 7 | Viewed by 2821
Abstract
In recent years, Mycobacterium abscessus has appeared as an emerging pathogen, with an increasing number of disease cases reported worldwide that mainly occur among patients with chronic lung diseases or impaired immune systems. The treatment of this pathogen represents a challenge due to [...] Read more.
In recent years, Mycobacterium abscessus has appeared as an emerging pathogen, with an increasing number of disease cases reported worldwide that mainly occur among patients with chronic lung diseases or impaired immune systems. The treatment of this pathogen represents a challenge due to the multi-drug-resistant nature of this species and its ability to evade most therapeutic approaches. However, although predisposing host factors for disease are well known, intrinsic pathogenicity mechanisms of this mycobacterium are still not elucidated. Like other mycobacteria, intracellular invasiveness and survival inside different cell lines are pathogenic factors related to the ability of M. abscessus to establish infection. Some of the molecular factors involved in this process are well-known and are present in the mycobacterial cell wall, such as trehalose-dimycolate and glycopeptidolipids. The ability to form biofilms is another pathogenic factor that is essential for the development of chronic disease and for promoting mycobacterial survival against the host immune system or different antibacterial treatments. This capability also seems to be related to glycopeptidolipids and other lipid molecules, and some studies have shown an intrinsic relationship between both pathogenic mechanisms. Antimicrobial resistance is also considered a mechanism of pathogenicity because it allows the mycobacterium to resist antimicrobial therapies and represents an advantage in polymicrobial biofilms. The recent description of hyperpathogenic strains with the potential interhuman transmission makes it necessary to increase our knowledge of pathogenic mechanisms of this species to design better therapeutic approaches to the management of these infections. Full article
(This article belongs to the Special Issue Mycobacterium abscessus: Current Knowledgement on an Emerging Pathogen)
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