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Advances in Molecular Biology on Mycobacteria
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Advances in Molecular Biology on Mycobacteria

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 4540

Special Issue Editor

Prof. Dr. Rita Macedo

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Guest Editor
National Reference Laboratory for Mycobacteria, Department of Infectious Diseases, National Institute of Health, Lisbon, Portugal
Interests: mycobacteria

Special Issue Information

Dear Colleagues,

First discovered in 1874 by Armauer Hansen, the genus Mycobacterium, with more than 220 species known to date, is the only genus of the Mycobacteriaceae family. Commonly, they are subdivided into three different groups—the members of the Mycobacterium tuberculosis complex (MTC), Mycobacterium leprae and non-tuberculous mycobacteria (NTM)—that can be classified into strict pathogens (MTC, M. leprae and some NTM), and opportunistic and saprophyte species (the majority of NTM). MTC members have already been declared as a world health problem and a public health threat; however, NTM are emerging as severe disease causative agents and there is a need to enhance its management, as correct identification is essential for diagnosis and eventual outbreak detection.

For this Special Issue of IJMS, we intend to focus on recent developments regarding diagnosis, resistance detection and molecular surveillance using molecular methodologies and research on the members of the genus Mycobacterium. Original research papers and up-to-date review articles are welcome.

Prof. Dr. Rita Macedo
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • genus Mycobacterium
  • non-tuberculous mycobacteria
  • Mycobacterium tuberculosis
  • Mycobacterium leprae
  • molecular diagnosis
  • molecular surveillance methodologies
  • molecular resistance prediction

Published Papers (5 papers)

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Research

18 pages, 4260 KiB  
Article
Rescue of Mycobacterium bovis DNA Obtained from Cultured Samples during Official Surveillance of Animal TB: Key Steps for Robust Whole Genome Sequence Data Generation
by Daniela Pinto, Gonçalo Themudo, André C. Pereira, Ana Botelho and Mónica V. Cunha
Int. J. Mol. Sci. 2024, 25(7), 3869; https://doi.org/10.3390/ijms25073869 - 30 Mar 2024
Viewed by 502
Abstract
Epidemiological surveillance of animal tuberculosis (TB) based on whole genome sequencing (WGS) of Mycobacterium bovis has recently gained track due to its high resolution to identify infection sources, characterize the pathogen population structure, and facilitate contact tracing. However, the workflow from bacterial isolation [...] Read more.
Epidemiological surveillance of animal tuberculosis (TB) based on whole genome sequencing (WGS) of Mycobacterium bovis has recently gained track due to its high resolution to identify infection sources, characterize the pathogen population structure, and facilitate contact tracing. However, the workflow from bacterial isolation to sequence data analysis has several technical challenges that may severely impact the power to understand the epidemiological scenario and inform outbreak response. While trying to use archived DNA from cultured samples obtained during routine official surveillance of animal TB in Portugal, we struggled against three major challenges: the low amount of M. bovis DNA obtained from routinely processed animal samples; the lack of purity of M. bovis DNA, i.e., high levels of contamination with DNA from other organisms; and the co-occurrence of more than one M. bovis strain per sample (within-host mixed infection). The loss of isolated genomes generates missed links in transmission chain reconstruction, hampering the biological and epidemiological interpretation of data as a whole. Upon identification of these challenges, we implemented an integrated solution framework based on whole genome amplification and a dedicated computational pipeline to minimize their effects and recover as many genomes as possible. With the approaches described herein, we were able to recover 62 out of 100 samples that would have otherwise been lost. Based on these results, we discuss adjustments that should be made in official and research laboratories to facilitate the sequential implementation of bacteriological culture, PCR, downstream genomics, and computational-based methods. All of this in a time frame supporting data-driven intervention. Full article
(This article belongs to the Special Issue Advances in Molecular Biology on Mycobacteria)
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21 pages, 7130 KiB  
Article
Differential Immunogenicity and Lung Disease-Inducing Potential of Mycobacterium immunogenum Genotypes and Impact of Co-Exposure with Pseudomonas: Optimizing a Mouse Model of Chronic Hypersensitivity Pneumonitis
by Elisabet Johansson and Jagjit S. Yadav
Int. J. Mol. Sci. 2024, 25(4), 2058; https://doi.org/10.3390/ijms25042058 - 8 Feb 2024
Viewed by 581
Abstract
Mycobacterium immunogenum (MI) colonizing metalworking fluids (MWFs) has been associated with chronic hypersensitivity pneumonitis (HP) in machinists. However, it is etiologically unclear why only certain mycobacteria-contaminated fluids induce this interstitial lung disease. We hypothesized that this may be due to differential immunogenicity and [...] Read more.
Mycobacterium immunogenum (MI) colonizing metalworking fluids (MWFs) has been associated with chronic hypersensitivity pneumonitis (HP) in machinists. However, it is etiologically unclear why only certain mycobacteria-contaminated fluids induce this interstitial lung disease. We hypothesized that this may be due to differential immunogenicity and the HP-inducing potential of MI strains/genotypes as well as the confounding effect of co-inhaled endotoxin-producers. To test this hypothesis, we optimized a chronic HP mouse model in terms of MI antigen dose, timepoint of sacrifice, and form of antigen (cell lysates vs. live cells) and compared six different field-isolated MI strains. Overall, MJY10 was identified as the most immunogenic and MJY4 (or MJY13) as the least immunogenic genotype based on lung pathoimmunological changes as well as Th1 cellular response (IFN-γ release). Infection with MI live cells induced a more severe phenotype than MI cell lysate. Co-exposure with Pseudomonas fluorescens caused a greater degree of lung innate immune response and granuloma formation but a diminished adaptive (Th1) immune response (IFN-γ) in the lung and spleen. In summary, this study led to the first demonstration of differential immunogenicity and the disease-inducing potential of field strains of MI and an interfering effect of the co-contaminating Pseudomonas. The improved chronic MI-HP mouse model and the identified polar pair of MI strains will facilitate future diagnostic and therapeutic research on this poorly understood environmental lung disease. Full article
(This article belongs to the Special Issue Advances in Molecular Biology on Mycobacteria)
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13 pages, 7025 KiB  
Article
Epinephrine Stimulates Mycobacterium tuberculosis Growth and Biofilm Formation
by Yingying Lei, Khaista Rahman, Xiaojian Cao, Bing Yang, Wei Zhou, Aikebaier Reheman, Luxia Cai, Yifan Wang, Rohit Tyagi, Zhe Wang, Xi Chen and Gang Cao
Int. J. Mol. Sci. 2023, 24(24), 17370; https://doi.org/10.3390/ijms242417370 - 12 Dec 2023
Viewed by 1134
Abstract
The human stress hormones catecholamines play a critical role in communication between human microbiota and their hosts and influence the outcomes of bacterial infections. However, it is unclear how M. tuberculosis senses and responds to certain types of human stress hormones. In this [...] Read more.
The human stress hormones catecholamines play a critical role in communication between human microbiota and their hosts and influence the outcomes of bacterial infections. However, it is unclear how M. tuberculosis senses and responds to certain types of human stress hormones. In this study, we screened several human catecholamine stress hormones (epinephrine, norepinephrine, and dopamine) for their effects on Mycobacterium growth. Our results showed that epinephrine significantly stimulated the growth of M. tuberculosis in the serum-based medium as well as macrophages. In silico analysis and molecular docking suggested that the extra-cytoplasmic domain of the MprB might be the putative adrenergic sensor. Furthermore, we showed that epinephrine significantly enhances M. tuberculosis biofilm formation, which has distinct texture composition, antibiotic resistance, and stress tolerance. Together, our data revealed the effect and mechanism of epinephrine on the growth and biofilm formation of M. tuberculosis, which contributes to the understanding of the environmental perception and antibiotic resistance of M. tuberculosis and provides important clues for the understanding of bacterial pathogenesis and the development of novel antibacterial therapeutics. Full article
(This article belongs to the Special Issue Advances in Molecular Biology on Mycobacteria)
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16 pages, 3410 KiB  
Article
Genome-Scale Characterization of Mycobacterium abscessus Complex Isolates from Portugal
by Sofia Carneiro, Miguel Pinto, Sónia Silva, Andrea Santos, Irene Rodrigues, Daniela Santos, Sílvia Duarte, Luís Vieira, João Paulo Gomes and Rita Macedo
Int. J. Mol. Sci. 2023, 24(20), 15402; https://doi.org/10.3390/ijms242015402 - 20 Oct 2023
Viewed by 883
Abstract
The Mycobacterium abscessus complex (MABC) is an emerging, difficult to treat, multidrug-resistant nontuberculous mycobacteria responsible for a wide spectrum of infections and associated with an increasing number of cases worldwide. Dominant circulating clones (DCCs) of MABC have been genetically identified as groups of [...] Read more.
The Mycobacterium abscessus complex (MABC) is an emerging, difficult to treat, multidrug-resistant nontuberculous mycobacteria responsible for a wide spectrum of infections and associated with an increasing number of cases worldwide. Dominant circulating clones (DCCs) of MABC have been genetically identified as groups of strains associated with higher prevalence, higher levels of antimicrobial resistance, and worse clinical outcomes. To date, little is known about the genomic characteristics of MABC species circulating in Portugal. Here, we examined the genetic diversity and antimicrobial resistance profiles of 30 MABC strains isolated between 2014 and 2022 in Portugal. The genetic diversity of circulating MABC strains was assessed through a gene-by-gene approach (wgMLST), allowing their subspecies differentiation and the classification of isolates into DCCs. Antimicrobial resistance profiles were defined using phenotypic, molecular, and genomic approaches. The majority of isolates were resistant to at least two antimicrobials, although a poor correlation between phenotype and genotype data was observed. Portuguese genomes were highly diverse, and data suggest the existence of MABC lineages with potential international circulation or cross-border transmission. This study highlights the genetic diversity and antimicrobial resistance profile of circulating MABC isolates in Portugal while representing the first step towards the implementation of a genomic-based surveillance system for MABC at the Portuguese NIH. Full article
(This article belongs to the Special Issue Advances in Molecular Biology on Mycobacteria)
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18 pages, 3070 KiB  
Article
Dynamic Transcriptional Landscape of Mycobacterium smegmatis under Cold Stress
by Artem S. Grigorov, Yulia V. Skvortsova, Oksana S. Bychenko, Leonid V. Aseev, Ludmila S. Koledinskaya, Irina V. Boni and Tatyana L. Azhikina
Int. J. Mol. Sci. 2023, 24(16), 12706; https://doi.org/10.3390/ijms241612706 - 11 Aug 2023
Viewed by 1010
Abstract
Bacterial adaptation to cold stress requires wide transcriptional reprogramming. However, the knowledge of molecular mechanisms underlying the cold stress response of mycobacteria is limited. We conducted comparative transcriptomic analysis of Mycobacterium smegmatis subjected to cold shock. The growth of M. smegmatis cultivated at [...] Read more.
Bacterial adaptation to cold stress requires wide transcriptional reprogramming. However, the knowledge of molecular mechanisms underlying the cold stress response of mycobacteria is limited. We conducted comparative transcriptomic analysis of Mycobacterium smegmatis subjected to cold shock. The growth of M. smegmatis cultivated at 37 °C was arrested just after exposure to cold (acclimation phase) but later (by 24 h) was resumed at a much slower rate (adaptation phase). Transcriptomic analyses revealed distinct gene expression patterns corresponding to the two phases. During the acclimation phase, differential expression was observed for genes associated with cell wall remodeling, starvation response, and osmotic pressure stress, in parallel with global changes in the expression of transcription factors and the downregulation of ribosomal genes, suggesting an energy-saving strategy to support survival. At the adaptation phase, the expression profiles were recovered, indicating restoration of the processes repressed earlier. Comparison of transcriptional responses in M. smegmatis with those in other bacteria revealed unique adaptation strategies developed by mycobacteria. Our findings shed light on the molecular mechanisms underlying M. smegmatis survival under cold stress. Further research should clarify whether the discovered transcriptional mechanisms exist in other mycobacterial species, including pathogenic Mycobacterium tuberculosis, which could be important for transmission control. Full article
(This article belongs to the Special Issue Advances in Molecular Biology on Mycobacteria)
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