MiR-495 regulates cellular ROS levels by targeting sod2 to inhibit intracellular survival of Mycobacterium tuberculosis in macrophages

Mycobacterium tuberculosis is a chronic infectious disease pathogen. To date, tuberculosis is a major infectious disease that endangers human health. To better prevent and treat tuberculosis, it is important to study the pathogenesis of M. tb . Based on early-stage laboratory research results, in this study, we verified the upregulation of sod2 in Bacillus Calmette–Guérin ( BCG ) and H37Rv infection. By detecting BCG / H37Rv intracellular survival in sod2 -silenced and sod2 - overexpressing macrophages, sod2 was found to promote the intracellular survival of BCG / H37Rv. Then, miR-495 was determined to be downregulated by BCG / H37Rv . BCG / H37Rv can upregulate sod2 expression by miR-495 to promote the intracellular survival of BCG / H37Rv through a decline in ROS levels. This study provides a theoretical basis for developing new drug targets and treating tuberculosis.

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Editorial on Special Issue “Tuberculosis Drug Discovery and Development 2019”

Applied Sciences ◽

10.3390/app10176069 ◽

2020 ◽

Vol 10 (17) ◽

pp. 6069

Author(s):

Claudia Sala ◽

Laurent Roberto Chiarelli ◽

Giovanna Riccardi

Keyword(s):

Infectious Disease ◽

Mycobacterium Tuberculosis ◽

Drug Discovery ◽

Human Health ◽

Cause Of Death ◽

Etiological Agent ◽

Special Issue ◽

Drug Discovery And Development ◽

Global Challenge

Mycobacterium tuberculosis, the etiological agent of human tuberculosis (TB), represents a global challenge to human health since it is the main cause of death by an infectious disease worldwide [...]

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Targeting Non-Replicating Mycobacterium tuberculosis and Latent Infection: Alternatives and Perspectives (Mini-Review)

International Journal of Molecular Sciences ◽

10.3390/ijms222413317 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13317

Author(s):

Anna Egorova ◽

Elena G. Salina ◽

Vadim Makarov

Keyword(s):

Mycobacterium Tuberculosis ◽

Small Molecules ◽

Drug Targets ◽

Latent Infection ◽

Early Stage ◽

Control Strategies ◽

Latent Tuberculosis ◽

Ltbi Treatment ◽

Latent Tb ◽

Current Guidelines

Latent tuberculosis infection (LTBI) represents a major challenge to curing TB disease. Current guidelines for LTBI management include only three older drugs and their combinations—isoniazid and rifamycins (rifampicin and rifapentine). These available control strategies have little impact on latent TB elimination, and new specific therapeutics are urgently needed. In the present mini-review, we highlight some of the alternatives that may potentially be included in LTBI treatment recommendations and a list of early-stage prospective small molecules that act on drug targets specific for Mycobacterium tuberculosis latency.

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Novel Flu Viruses in Bats and Cattle: “Pushing the Envelope” of Influenza Infection

Veterinary Sciences ◽

10.3390/vetsci5030071 ◽

2018 ◽

Vol 5 (3) ◽

pp. 71 ◽

Cited By ~ 5

Author(s):

Suresh Kuchipudi ◽

Ruth Nissly

Keyword(s):

Infectious Disease ◽

Influenza Virus ◽

Host Range ◽

Human Health ◽

Influenza Infection ◽

Influenza Viruses ◽

Geographic Boundaries ◽

Major Infectious Disease ◽

Virus Host Range

Influenza viruses are among the major infectious disease threats of animal and human health. This review examines the recent discovery of novel influenza viruses in bats and cattle, the evolving complexity of influenza virus host range including the ability to cross species barriers and geographic boundaries, and implications to animal and human health.

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Adenylating Enzymes in Mycobacterium tuberculosis as Drug Targets

Current Topics in Medicinal Chemistry ◽

10.2174/156802612799984571 ◽

2012 ◽

Vol 12 (7) ◽

pp. 766-796 ◽

Cited By ~ 37

Author(s):

Benjamin P. Duckworth ◽

Kathryn M. Nelson ◽

Courtney C. Aldrich

Keyword(s):

Mycobacterium Tuberculosis ◽

Drug Targets

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Exploration of Ion Channels in Mycobacterium tuberculosis: Implication on Drug Discovery and Potent Drug Targets Against Tuberculosis

Current Chemical Biology ◽

10.2174/2212796814666200310100746 ◽

2020 ◽

Vol 14 (1) ◽

pp. 14-29

Author(s):

Manish Dwivedi

Keyword(s):

Mycobacterium Tuberculosis ◽

Drug Targets ◽

Cell Envelope ◽

Intracellular Pathogen ◽

Host Immune System ◽

Transporter Proteins ◽

Channel Proteins ◽

Medical Importance ◽

Potent Drug ◽

Emergence Of Resistance

Scientific interest in mycobacteria has been sparked by the medical importance of Mycobacterium tuberculosis (Mtb) that is known to cause severe diseases in mammals, i.e. tuberculosis and by properties that distinguish them from other microorganisms which are notoriously difficult to treat. The treatment of their infections is difficult because mycobacteria fortify themselves with a thick impermeable cell envelope. Channel and transporter proteins are among the crucial adaptations of Mycobacterium that facilitate their strength to combat against host immune system and anti-tuberculosis drugs. In previous studies, it was investigated that some of the channel proteins contribute to the overall antibiotic resistance in Mtb. Moreover, in some of the cases, membrane proteins were found responsible for virulence of these pathogens. Given the ability of M. tuberculosis to survive as an intracellular pathogen and its inclination to develop resistance to the prevailing anti-tuberculosis drugs, its treatment requires new approaches and optimization of anti-TB drugs and investigation of new targets are needed for their potential in clinical usage. Therefore, it is imperative to investigate the survival of Mtb. in stressed conditions with different behavior of particular channel/ transporter proteins. Comprehensive understanding of channel proteins and their mechanism will provide us direction to find out preventive measures against the emergence of resistance and reduce the duration of the treatment, eventually leading to plausible eradication of tuberculosis.

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Huanglongbing Model under the Control Strategy of Discontinuous Removal of Infected Trees

Symmetry ◽

10.3390/sym13071164 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1164

Author(s):

Weiwei Ling ◽

Pinxia Wu ◽

Xiumei Li ◽

Liangjin Xie

Keyword(s):

Infectious Disease ◽

Global Stability ◽

Control Strategy ◽

Theoretical Basis ◽

Dynamic Properties ◽

Transmission Mechanism ◽

Basic Reproductive Number ◽

Reproductive Number ◽

Vector Borne ◽

Citrus Trees

By using differential equations with discontinuous right-hand sides, a dynamic model for vector-borne infectious disease under the discontinuous removal of infected trees was established after understanding the transmission mechanism of Huanglongbing (HLB) disease in citrus trees. Through calculation, the basic reproductive number of the model can be attained and the properties of the model are discussed. On this basis, the existence and global stability of the calculated equilibria are verified. Moreover, it was found that different I0 in the control strategy cannot change the dynamic properties of HLB disease. However, the lower the value of I0, the fewer HLB-infected citrus trees, which provides a theoretical basis for controlling HLB disease and reducing expenditure.

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Contagion Management at the Méditerranée Infection University Hospital Institute

Journal of Clinical Medicine ◽

10.3390/jcm10122627 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2627

Author(s):

Pierre-Edouard Fournier ◽

Sophie Edouard ◽

Nathalie Wurtz ◽

Justine Raclot ◽

Marion Bechet ◽

...

Keyword(s):

Infectious Disease ◽

Early Diagnosis ◽

Personal Protective Equipment ◽

Early Stage ◽

Point Of Care ◽

University Hospital ◽

Protective Equipment ◽

Monitoring Point ◽

Epidemiological Monitoring ◽

Wide Range

The Méditerranée Infection University Hospital Institute (IHU) is located in a recent building, which includes experts on a wide range of infectious disease. The IHU strategy is to develop innovative tools, including epidemiological monitoring, point-of-care laboratories, and the ability to mass screen the population. In this study, we review the strategy and guidelines proposed by the IHU and its application to the COVID-19 pandemic and summarise the various challenges it raises. Early diagnosis enables contagious patients to be isolated and treatment to be initiated at an early stage to reduce the microbial load and contagiousness. In the context of the COVID-19 pandemic, we had to deal with a shortage of personal protective equipment and reagents and a massive influx of patients. Between 27 January 2020 and 5 January 2021, 434,925 nasopharyngeal samples were tested for the presence of SARS-CoV-2. Of them, 12,055 patients with COVID-19 were followed up in our out-patient clinic, and 1888 patients were hospitalised in the Institute. By constantly adapting our strategy to the ongoing situation, the IHU has succeeded in expanding and upgrading its equipment and improving circuits and flows to better manage infected patients.

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Label-Free Comparative Proteomics of Differentially Expressed Mycobacterium tuberculosis Protein in Rifampicin-Related Drug-Resistant Strains

Pathogens ◽

10.3390/pathogens10050607 ◽

2021 ◽

Vol 10 (5) ◽

pp. 607

Author(s):

Nadeem Ullah ◽

Ling Hao ◽

Jo-Lewis Banga Ndzouboukou ◽

Shiyun Chen ◽

Yaqi Wu ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Drug Targets ◽

Control Strategies ◽

Multidrug Resistant ◽

Differentially Expressed ◽

Effective Control ◽

Drug Resistant ◽

Differentially Expressed Proteins ◽

Label Free ◽

Candidate Target

Rifampicin (RIF) is one of the most important first-line anti-tuberculosis (TB) drugs, and more than 90% of RIF-resistant (RR) Mycobacterium tuberculosis clinical isolates belong to multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. In order to identify specific candidate target proteins as diagnostic markers or drug targets, differential protein expression between drug-sensitive (DS) and drug-resistant (DR) strains remains to be investigated. In the present study, a label-free, quantitative proteomics technique was performed to compare the proteome of DS, RR, MDR, and XDR clinical strains. We found iniC, Rv2141c, folB, and Rv2561 were up-regulated in both RR and MDR strains, while fadE9, espB, espL, esxK, and Rv3175 were down-regulated in the three DR strains when compared to the DS strain. In addition, lprF, mce2R, mce2B, and Rv2627c were specifically expressed in the three DR strains, and 41 proteins were not detected in the DS strain. Functional category showed that these differentially expressed proteins were mainly involved in the cell wall and cell processes. When compared to the RR strain, Rv2272, smtB, lpqB, icd1, and folK were up-regulated, while esxK, PPE19, Rv1534, rpmI, ureA, tpx, mpt64, frr, Rv3678c, esxB, esxA, and espL were down-regulated in both MDR and XDR strains. Additionally, nrp, PPE3, mntH, Rv1188, Rv1473, nadB, PPE36, and sseA were specifically expressed in both MDR and XDR strains, whereas 292 proteins were not identified when compared to the RR strain. When compared between MDR and XDR strains, 52 proteins were up-regulated, while 45 proteins were down-regulated in the XDR strain. 316 proteins were especially expressed in the XDR strain, while 92 proteins were especially detected in the MDR strain. Protein interaction networks further revealed the mechanism of their involvement in virulence and drug resistance. Therefore, these differentially expressed proteins are of great significance for exploring effective control strategies of DR-TB.

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