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Molecular Research in Infective 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: 20 June 2025 | Viewed by 5494

Special Issue Editor


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Guest Editor
Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Via A. Ferrata 9, 27100 Pavia, Italy
Interests: bacterial biochemistry; enzymes; target identification; drug development; mycobacteria; infectious diseases; antimicrobial resistance; metabolites; computational approaches
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Special Issue Information

Dear Colleagues,

Research on mycobacteria is expanding thanks to the identification of emerging nontuberculous mycobacteria (NTM) pathogens like the opportunistic Mycobacterium abscessus complex, M. fortuitum, M. chelonae, or M. immunogenum. However, therapeutic approaches against NTM infections lack specificity, mainly relying on repurposed drugs originally developed for other pathogens such as M. tuberculosis or avium. In addition, mycobacteria are drawing particular attention for their peculiar features, such as their innate and acquired resistance to many drugs through a plethora of strategies.

This Special Issue aims to collect the most recent original papers and reviews on infectious mycobacteria, and will encompass well-known species like M. tuberculosis, avium and marium as well as the emerging NTM pathogens, with particular emphasis on molecular-level investigations.

Dr. Giovanni Stelitano
Guest Editor

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Keywords

  • infections
  • mycobacteria
  • molecular biology
  • antimicrobials
  • bacteria biochemistry

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Published Papers (4 papers)

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Research

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15 pages, 6113 KiB  
Article
NHERF2 as a Novel Biomarker for Distinguishing MAC Pulmonary Disease from Tuberculosis Based on Proteome Analysis of Serum Extracellular Vesicles
by Maiko Naito, Yoshito Takeda, Ryuya Edahiro, Yuya Shirai, Takatoshi Enomoto, Mana Nakayama, Satoshi Nojima, Mari Nogami-Ito, Masahide Mori, Yukihiro Yano, Takanori Matsuki, Hanako Yoshimura, Reina Hara, Makoto Yamamoto, Kentaro Masuhiro, Yujiro Naito, Shohei Koyama, Kota Iwahori, Izumi Nagatomo, Takayuki Shiroyama, Kotaro Miyake, Haruhiko Hirata, Hiroaki Hase, Kazutake Tsujikawa, Koji Ueda and Atsushi Kumanogohadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2025, 26(3), 1155; https://doi.org/10.3390/ijms26031155 - 29 Jan 2025
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Abstract
Nontuberculous mycobacterial pulmonary disease (NTM-PD), mainly caused by Mycobacterium avium complex (MAC), and pulmonary tuberculosis (TB) are emerging health problems worldwide. However, because their clinical features are often similar, it remains difficult to differentiate NTM-PD from TB when the diagnosis cannot be made [...] Read more.
Nontuberculous mycobacterial pulmonary disease (NTM-PD), mainly caused by Mycobacterium avium complex (MAC), and pulmonary tuberculosis (TB) are emerging health problems worldwide. However, because their clinical features are often similar, it remains difficult to differentiate NTM-PD from TB when the diagnosis cannot be made by sputum culture. To investigate potential serum biomarkers, we conducted non-targeted proteome analysis on serum extracellular vesicles (EVs) collected from 10 patients with MAC pulmonary disease (MAC-PD), 7 patients with TB, and 10 healthy controls. A total of 2614 proteins were identified in the discovery cohort. The EV protein signature from patients with NTM-PD and TB reflected infectious diseases and inflammatory response pathways. Among the identified proteins, the expression of Na+/H+ exchanger regulatory factor 2 (NHERF2) was significantly elevated in patients with MAC-PD compared with healthy controls and patients with TB. Moreover, upregulation of NHERF2 was confirmed by immunoblotting of serum EVs and immunohistochemistry of lungs with mycobacterial infection. Our findings highlight that NHERF2 in serum EVs might be a potential biomarker for distinguishing MAC-PD from TB, possibly reflecting the pathogenesis of MAC-PD. Full article
(This article belongs to the Special Issue Molecular Research in Infective Mycobacteria)
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11 pages, 2647 KiB  
Article
Structure-Based Screening and Optimization of PafA Inhibitors with Potent Anti-Tuberculosis Activity
by Hewei Jiang, Jin Xie, Lei Wang, Hong Chen, Yunxiao Zheng, Xuening Wang, Shujuan Guo, Tao Wang, Jing Bi, Xuelian Zhang, Jianfeng Pei and Shengce Tao
Int. J. Mol. Sci. 2024, 25(23), 13189; https://doi.org/10.3390/ijms252313189 - 8 Dec 2024
Viewed by 1144
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health challenge, primarily due to the increasing prevalence of drug resistance. Consequently, the development of drugs with novel modes of action (MOAs) is urgently required. In this study, we discovered [...] Read more.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health challenge, primarily due to the increasing prevalence of drug resistance. Consequently, the development of drugs with novel modes of action (MOAs) is urgently required. In this study, we discovered and characterized two potent inhibitors, Pi-1-58 and Pi-2-26, targeting the prokaryotic ubiquitin-like protein (Pup) ligase PafA of Mtb. Pi-1-58 was identified through computer-aided drug screening. The binding mode of Pi-1-58 and PafA was investigated through molecular docking, followed by experimental validations. Based on the core structure of Pi-1-58, we developed a more potent inhibitor, Pi-2-26, through structure-guided drug design. Both Pi-1-58 and Pi-2-26 exhibited selective and specific inhibition of PafA according to biochemical and cell-based assays. Importantly, the inhibitors demonstrated significant inhibition on Mtb survival in the presence of nitric oxide, mimicking the in vivo nitrogen limited environment that Mtb encountered in macrophage. Our findings provide a comprehensive understanding of the structural and functional aspects of these PafA inhibitors and establish a solid foundation for the development of novel therapeutics against tuberculosis. Full article
(This article belongs to the Special Issue Molecular Research in Infective Mycobacteria)
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19 pages, 1185 KiB  
Article
Retrospective Single Nucleotide Polymorphism Analysis of Host Resistance and Susceptibility to Ovine Johne’s Disease Using Restored FFPE DNA
by Amanda Kravitz, Mingsi Liao, Gota Morota, Ron Tyler, Rebecca Cockrum, B. Murali Manohar, B. Samuel Masilamoni Ronald, Michael T. Collins and Nammalwar Sriranganathan
Int. J. Mol. Sci. 2024, 25(14), 7748; https://doi.org/10.3390/ijms25147748 - 15 Jul 2024
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Abstract
Johne’s disease (JD), also known as paratuberculosis, is a chronic, untreatable gastroenteritis of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection. Evidence for host genetic resistance to disease progression exists, although it is limited due to the extended incubation period (years) and [...] Read more.
Johne’s disease (JD), also known as paratuberculosis, is a chronic, untreatable gastroenteritis of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection. Evidence for host genetic resistance to disease progression exists, although it is limited due to the extended incubation period (years) and diagnostic challenges. To overcome this, previously restored formalin-fixed paraffin embedded tissue (FFPE) DNA from archived FFPE tissue cassettes was utilized for a novel retrospective case-control genome-wide association study (GWAS) on ovine JD. Samples from known MAP-infected flocks with ante- and postmortem diagnostic data were used. Cases (N = 9) had evidence of tissue infection, compared to controls (N = 25) without evidence of tissue infection despite positive antemortem diagnostics. A genome-wide efficient mixed model analysis (GEMMA) to conduct a GWAS using restored FFPE DNA SNP results from the Illumina Ovine SNP50 Bead Chip, identified 10 SNPs reaching genome-wide significance of p < 1 × 10−6 on chromosomes 1, 3, 4, 24, and 26. Pathway analysis using PANTHER and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was completed on 45 genes found within 1 Mb of significant SNPs. Our work provides a framework for the novel use of archived FFPE tissues for animal genetic studies in complex diseases and further evidence for a genetic association in JD. Full article
(This article belongs to the Special Issue Molecular Research in Infective Mycobacteria)
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Review

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15 pages, 1010 KiB  
Review
Mycobacterium abscessus Virulence Factors: An Overview of Un-Explored Therapeutic Options
by Mario Cocorullo, Alessandro Stamilla, Deborah Recchia, Maria Concetta Marturano, Ludovica Maci and Giovanni Stelitano
Int. J. Mol. Sci. 2025, 26(7), 3247; https://doi.org/10.3390/ijms26073247 - 31 Mar 2025
Viewed by 473
Abstract
Mycobacterium abscessus (Mab) is an opportunistic pathogen gaining increased importance due to its capacity to colonize the respiratory tract of patients with chronic lung diseases such as individuals with Cystic Fibrosis. The actual therapeutic regimen to treat Mab infections is based [...] Read more.
Mycobacterium abscessus (Mab) is an opportunistic pathogen gaining increased importance due to its capacity to colonize the respiratory tract of patients with chronic lung diseases such as individuals with Cystic Fibrosis. The actual therapeutic regimen to treat Mab infections is based on repurposed drugs from therapies against Mycobacterium tuberculosis and avium. In addition to the need for new specific drugs against this bacterium, a possible strategy for shortening the therapeutic time and improving the success rate could be targeting Mab virulence factors. These drugs could become an important integration to the actual therapeutic regimen, helping the immune system to fight the infection. Moreover, this strategy applies a low selective pressure on the bacteria, since these elements are not essential for Mab survival but crucial for establishing the infection. This review aims to provide an overview of the Mab’s virulence factors that are poorly studied and mostly unknown, suggesting some interesting alternatives to classical drug development. Full article
(This article belongs to the Special Issue Molecular Research in Infective Mycobacteria)
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