Sirtuin2 blockade inhibits replication of Human Immunodeficiency Virus-1 and 1 Mycobacterium tuberculosis in macrophages and humanized mice DOI Open Access
Vipul K. Singh, Abhishek Mishra,

Kent Truong

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

ABSTRACT Coinfections with Mycobacterium tuberculosis (Mtb) and HIV-1 present a critical health challenge require treatment for survival. We found that human M1 macrophages inhibit Mtb growth, while M2 macrophages, characterized by elevated Sirt2 expression, permit growth. Further, we augmented gene expression in MФs. Therefore, explored the therapeutic potential of sirtuin-modulating drugs Sirtinol, inhibitor, significantly reduced growth M0, M1, M2-MФs >1 log10 over 7 days. Conversely, individual doses resveratrol SRT1460, which activate Sirt1, did not affect HIV-1. However, their combination showed strong synergistic inhibition The sirtinol was neither nor antagonistic. Sirtinol upregulated iNOS ATG5 mRNA infected MФs phenotype-dependent manner. In humanized mouse model (Hu-NSG-SGM3) co-infected H37Rv BAL strain, alone, or antiretroviral therapy (cART), promising results; alone its cART effectively inhibited replication organs. propose blockade Sirt1-activation represent novel dual strategy treating coinfections.

Language: Английский

A Comprehensive Review on Phage Therapy and Phage-Based Drug Development DOI Creative Commons
Longzhu Cui, Shinya Watanabe, Kazuhiko Miyanaga

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(9), P. 870 - 870

Published: Sept. 11, 2024

Phage therapy, the use of bacteriophages (phages) to treat bacterial infections, is regaining momentum as a promising weapon against rising threat multidrug-resistant (MDR) bacteria. This comprehensive review explores historical context, modern resurgence phage and phage-facilitated advancements in medical technological fields. It details mechanisms action applications phages treating MDR particularly those associated with biofilms intracellular pathogens. The further highlights innovative uses vaccine development, cancer gene delivery vectors. Despite its targeted efficient approach, therapy faces challenges related stability, immune response, regulatory approval. By examining these areas detail, this underscores immense potential remaining hurdles integrating phage-based therapies into practices.

Language: Английский

Citations

17
Mycobacteriophages: therapeutic approach for mycobacterial infections DOI

Sunil Kumar Raman,

D.V. Siva Reddy,

Vikas Jain

et al.

Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(7), P. 104049 - 104049

Published: June 1, 2024

Language: Английский

Citations

4
Vic9 mycobacteriophage: the first subcluster B2 phage isolated in Russia DOI Creative Commons
Marina V. Zaychikova,

Maja V. Malakhova,

Dmitry Bespiatykh

et al.

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Mycobacteriophages are viruses that specifically infect bacteria of the Mycobacterium genus. A substantial collection mycobacteriophages has been isolated and characterized, offering valuable insights into their diversity evolution. This also holds significant potential for therapeutic applications, particularly as an alternative to antibiotics in combating drug-resistant bacterial strains. In this study, we report isolation characterization a new mycobacteriophage, Vic9, using smegmatis mc (2)155 host strain. Vic9 classified within B2 subcluster B cluster. Morphological analysis revealed structure typical siphophages from forms characteristic plaques. The phage adsorbs onto strain cells 30 min, according one-step growth experiments, its latent period lasts about 90 followed by 150 with average yield approximately 68 particles per infected cell. range efficiently lysed exhibited ability lyse M. tuberculosis H37Rv, albeit low efficiency plating (EOP ≈ 2 × 10-5), feature phages. No lysis was observed other tested mycobacterial species. genome comprises 67,543 bp double-stranded DNA encodes 89 open reading frames. Our unique features despite close relationship phages, highlighting distinct characteristics even among closely related Particularly noteworthy discovery 435 sequence gene cluster responsible queuosine biosynthesis, well recombination event structural cassette region (Vic_0033-Vic_0035) members B1, B2, B3 subclusters. These genetic interest further research, they may reveal mechanisms phage-bacteria interactions developing novel therapy methods.

Language: Английский

Citations

0
vB_Ent31 Bacteriophage May Combat Enterobacter cloacae Infections with Macrophage Modulating Activity DOI
Mengyuan Li,

Jiayue Ma,

Xiaoshuang Feng

et al.

Virology, Journal Year: 2025, Volume and Issue: 605, P. 110463 - 110463

Published: Feb. 25, 2025

Language: Английский

Citations

0
Recent Advances in Inhibitor Development and Metabolic Targeting in Tuberculosis Therapy DOI

Ritu Raj Patel,

Vidyasagar,

Sudhir Singh

et al.

Microbial Pathogenesis, Journal Year: 2025, Volume and Issue: unknown, P. 107515 - 107515

Published: March 1, 2025

Language: Английский

Citations

0
Cryo-EM reveals structural diversity in prolate-headed mycobacteriophage Mycofy1 DOI
Xiangyun Li, Qianqian Shao, Lin Li

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169126 - 169126

Published: April 1, 2025

Language: Английский

Citations

0
Advancing Phage Therapy: A Comprehensive Review of the Safety, Efficacy, and Future Prospects for the Targeted Treatment of Bacterial Infections DOI Creative Commons
Marco Palma, Ben-Quan Qi

Infectious Disease Reports, Journal Year: 2024, Volume and Issue: 16(6), P. 1127 - 1181

Published: Nov. 28, 2024

Background: Phage therapy, a treatment utilizing bacteriophages to combat bacterial infections, is gaining attention as promising alternative antibiotics, particularly for managing antibiotic-resistant bacteria. This study aims provide comprehensive review of phage therapy by examining its safety, efficacy, influencing factors, future prospects, and regulatory considerations. The also seeks identify strategies optimizing application propose systematic framework clinical implementation. Methods: A analysis preclinical studies, trials, frameworks was undertaken evaluate the therapeutic potential therapy. included an in-depth assessment key factors outcomes, such infection site, phage–host specificity, burden, immune response. Additionally, innovative strategies—such combination therapies, bioengineered phages, cocktails—were explored enhance efficacy. Critical considerations related dosing, including inoculum size, multiplicity infection, windows, personalized medicine approaches, were examined optimize outcomes. Results: has demonstrated favorable safety profile in both settings, with minimal adverse effects. Its ability specifically target harmful bacteria while preserving beneficial microbiota underpins efficacy treating range infections. However, variable outcomes some studies highlight importance addressing critical that influence success. Innovative expanded access diverse banks, cocktails, medicine, hold significant promise improving Optimizing dosing remains area enhancement, kinetics, resistance potential, frequency, patient-specific factors. To support streamlined four-step guideline been developed, providing effective planning Conclusion: offers highly adaptable, targeted, cost-effective approach While several must be thoroughly evaluated there improvement through refined methodologies. Although yet achieve widespread approval U.S. Europe, accessibility Expanded Access programs FDA authorizations food pathogen control underscores promise. Established practices countries Poland Georgia further demonstrate feasibility. enable broader adoption, harmonization advancements production, delivery, quality will essential. Notably, affordability scalability position it especially valuable solution developing regions grappling escalating rates antibiotic resistance.

Language: Английский

Citations

3
Dry Powder Inhalation of Lytic Mycobacteriophages for Adjunct Therapy in a Mouse Model of Infection with Mycobacterium tuberculosis DOI

Sunil Kumar Raman,

Trisha Roy, Khushboo Verma

et al.

Tuberculosis, Journal Year: 2025, Volume and Issue: 152, P. 102631 - 102631

Published: March 11, 2025

Language: Английский

Citations

0
Use of epigenetically modified bacteriophage and dual beta-lactams to treat a Mycobacterium abscessus sternal wound infection DOI Creative Commons

Madison Cristinziano,

Elena Shashkina,

Liang Chen

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 28, 2024

Abstract Nontuberculous mycobacterium (NTM) infections are challenging to manage and frequently non-responsive aggressive but poorly-tolerated antibiotic therapies. Immunosuppressed lung transplant patients susceptible NTM poor patient outcomes common. Bacteriophages present an alternative treatment option associated with favorable clinical outcomes. Similarly, dual beta-lactam combinations show promise in vitro, use is sparse. We report here a uncontrolled Mycobacterium abscessus infection following bilateral failed therapy. Both smooth rough colony morphotype strains were initially present, two phages that kill the strain – including epigenetic-modification overcome restriction resulted isolation of only strain. The have similar susceptibilities suggesting specifically eliminated Dual therapy meropenem ceftazidime-avibactam provided further improvement, act synergistically vitro.

Language: Английский

Citations

1
Humanized Mouse Models of Bacterial Infections DOI Creative Commons
Katya McDonald,

Adryiana Rodriguez,

Gowrishankar Muthukrishnan

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(7), P. 640 - 640

Published: July 11, 2024

Bacterial infections continue to represent a significant healthcare burden worldwide, causing considerable mortality and morbidity every year. The emergence of multidrug-resistant bacterial strains continues rise, posing serious risks controlling global disease outbreaks. To develop novel more effective treatment vaccination programs, there is need for clinically relevant small animal models. Since multiple species have human-specific tropism numerous virulence factors toxins, conventional mouse models do not fully human disease. Several characteristic phenotypes, such as lung granulomas in the case Mycobacterium tuberculosis infections, are absent standard Alternatively, certain pathogens, Salmonella enterica serovar typhi Staphylococcus aureus, can be well tolerated mice cleared quickly. address this, groups developed humanized observed enhanced susceptibility infection faithful recapitulation In last two decades, been attempt recapitulate immune system model. this review, we first discuss history immunodeficient that has enabled engraftment tissue methods currently used field. We then highlight how successfully uncovered critical responses various including Typhi, tuberculosis, aureus.

Language: Английский

Citations

0