Characterization of Novel Mycobacteriophages of Subcluster A3: Evolutionary Plasticity of the Lysogeny Module and Lytic Potential.
5 affiliations
- 1Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical Biological Agency, Moscow 119435, Russia.
- 2Moscow Center for Advanced Studies, Moscow 123592, Russia.
- 3Faculty of Biology, Lomonosov Moscow State University, Moscow 119991, Russia.
- 4Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow 119071, Russia.
- 5State Research Center for Applied Microbiology and Biotechnology, Obolensk 142279, Russia.
Abstract
The increasing prevalence of drug-resistant Mycobacteriumtuberculosis (Mtb) and nontuberculous mycobacteria (NTM) underscores the need for novel strategies. Mycobacteriophages are attracting growing interest for therapeutic and diagnostic applications. Here, we describe four new subcluster A3 phages (Cat, Goose1D, Goose1X, and Shep) and investigate their genomic diversity and lytic activity. The phages share >98% nucleotide identity with known A3 members but carry distinct deletions within the lysogeny module: Cat and Goose1X have different repressor-loss variants, and Goose1D lacks the integrase gene, whereas Shep retains an intact module. All phages lysed M. tuberculosis H37Rv, with efficiencies of plating (EOPs) of 10⁻²-10⁻¹, but showed limited activity against NTM. Cat was the most effective against drug-resistant Mtb isolates (EOPs of 10⁻¹-1), remained stable across a broad pH and temperature range, but had a low burst size (8 PFU (plaque-forming units/cell). In lysogeny assays, 6% of Cat-exposed M. smegmatis colonies exhibited a lysogen-like phenotype, but no phage DNA was detected, suggesting spontaneous resistance. Sequencing of one strain revealed an H535Q substitution in the pyruvate carboxylase MSMEG_2412. These findings highlight lysogeny module plasticity in closely related phages and position Cat, with its naturally occurring repressor deletion and potent lytic activity, as a promising candidate against drug-resistant tuberculosis.
Related
- Why development time matters: temperature influences plasticity while nutritional stress reshapes selection and evolutionary potential
- Genome-Wide Characterization of the DELLA Gene Family in Hevea brasiliensis Reveals Evolutionary Diversification and Potential HbDELLA3/4-HbbHLH25 Interaction.
- Differing components of plasticity in quantitative genetic threshold traits cause diverging eco-evolutionary responses to spatio-seasonal environmental deterioration
- Plasticity Decay and Attenuated Recovery (PDAR): A Hybrid Dynamical Model for the Historical Accessibility of Evolutionary Space
- Investigating the evolutionary plasticity of influenza virus splicing using influenza A virus segment 7 as a model system
BibTeX
@article{zaychikova2026characterization,
title = {{Characterization of Novel Mycobacteriophages of Subcluster A3: Evolutionary Plasticity of the Lysogeny Module and Lytic Potential.}},
author = {Marina Zaychikova and Maja Malakhova and Sofya Kuznetsova and Dmitry Bespiatykh and Sergei Kiselev and Ksenia Klimina and Aleksandra Strokach and Arina German and Anastasiia Lebedeva and Mikhail Fursov and Anna Vnukova and Dmitry Bagrov and Nadezda Trofimova and Margarita Shleeva and Egor Shitikov},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198476},
url = {https://europepmc.org/article/MED/42883726},
note = {CC BY},
}
RIS
TY - JOUR
TI - Characterization of Novel Mycobacteriophages of Subcluster A3: Evolutionary Plasticity of the Lysogeny Module and Lytic Potential.
AU - Marina Zaychikova
AU - Maja Malakhova
AU - Sofya Kuznetsova
AU - Dmitry Bespiatykh
AU - Sergei Kiselev
AU - Ksenia Klimina
AU - Aleksandra Strokach
AU - Arina German
AU - Anastasiia Lebedeva
AU - Mikhail Fursov
AU - Anna Vnukova
AU - Dmitry Bagrov
AU - Nadezda Trofimova
AU - Margarita Shleeva
AU - Egor Shitikov
PY - 2026
DA - 2026/09/23
JO - International journal of molecular sciences
DO - 10.3390/ijms27198476
UR - https://europepmc.org/article/MED/42883726
AB - The increasing prevalence of drug-resistant Mycobacteriumtuberculosis (Mtb) and nontuberculous mycobacteria (NTM) underscores the need for novel strategies. Mycobacteriophages are attracting growing interest for therapeutic and diagnostic applications. Here, we describe four new subcluster A3 phages (Cat, Goose1D, Goose1X, and Shep) and investigate their genomic diversity and lytic activity. The phages share >98% nucleotide identity with known A3 members but carry distinct deletions within the lysogeny module: Cat and Goose1X have different repressor-loss variants, and Goose1D lacks the integrase gene, whereas Shep retains an intact module. All phages lysed M. tuberculosis H37Rv, with efficiencies of plating (EOPs) of 10⁻²-10⁻¹, but showed limited activity against NTM. Cat was the most effective against drug-resistant Mtb isolates (EOPs of 10⁻¹-1), remained stable across a broad pH and temperature range, but had a low burst size (8 PFU (plaque-forming units/cell). In lysogeny assays, 6% of Cat-exposed M. smegmatis colonies exhibited a lysogen-like phenotype, but no phage DNA was detected, suggesting spontaneous resistance. Sequencing of one strain revealed an H535Q substitution in the pyruvate carboxylase MSMEG_2412. These findings highlight lysogeny module plasticity in closely related phages and position Cat, with its naturally occurring repressor deletion and potent lytic activity, as a promising candidate against drug-resistant tuberculosis.
SN - 1422-0067
ER -