Evidence map›Paper›PMID 35084027›Full record

ArticleThe Journal of antimicrobial chemotherapy2022

Intranasally administered S-MGB-364 displays antitubercular activity and modulates the host immune response to Mycobacterium tuberculosis infection.

Nathan S Kieswetter, Mumin Ozturk, Lerato Hlaka, Julius Ebua Chia, Ryan J O Nichol, Jasmine M Cross, Leah M C McGee, Izaak Tyson-Hirst, Rebecca Beveridge, Frank Brombacher and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. The allure of targets for novel drugs.RSC medicinal chemistry · 2024
    Review
  4. Article
  5. Article
  6. Article
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Nathan S KieswetterInternational Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town 7925, South Africa.
Mumin OzturkInternational Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town 7925, South Africa.
Lerato HlakaInternational Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town 7925, South Africa.
Julius Ebua ChiaInternational Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town 7925, South Africa.
Ryan J O NicholDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland.
Jasmine M CrossDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland.
Leah M C McGeeDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland.
Izaak Tyson-HirstDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland.
Rebecca BeveridgeDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland.
Frank BrombacherInternational Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town 7925, South Africa.
Katharine C CarterStrathclyde Institute of Pharmacy of Biomedical Sciences, University of Strathclyde, Glasgow G4 0NR, Scotland.
Colin J SucklingDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland.
Fraser J ScottDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland.
Reto GulerInternational Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town 7925, South Africa.
University of Strathclyde · GBInternational Centre for Genetic Engineering and Biotechnology · ZASouth African Medical Research Council · ZAUniversity of Cape Town · ZA

Funding

DSIICGEBInternational Centre for Genetic Engineering & BiotechnologyKnowledge Exchange Development FundMedical Research Council MR/T020970/1NRFSouth Africa Medical Research CouncilSouth African Research Chair InitiativeUKRIUniversity of StrathclydeUniversity of Strathclyde 110482Wellcome TrustWellcome Trust 203135/Z/16/ZWellcome Trust 210103_Z_18_Z
6 · The paper itself

Abstract

backgroundPreviously, we evaluated the intracellular mycobactericidal activity of the minor groove binder, S-MGB-364 against the clinical Mycobacterium tuberculosis (Mtb) strain HN878 in macrophages.

objectivesTo assess the mycobactericidal activity of S-MGB-364 in Mtb-infected mice. Further, we investigated a plausible DNA binding mechanism of action of S-MGB-364.

methodsThe anti-TB and host immune effects of intranasal S-MGB-364 or S-MGB-364 encapsulated in non-ionic surfactant vesicles (NIV) were assessed in Mtb-infected mice by cfu enumeration, ELISA, histology, and flow cytometry. DNA binding was examined using native mass spectrometry and UV-vis thermal melt determination. S-MGB interference with DNA-centric biological events was assessed using a representative panel of Mtb and human topoisomerase I, and gyrase assays.

resultsS-MGB-364 bound strongly to DNA as a dimer, significantly increasing the stability of the DNA:S-MGB complex compared with DNA alone. Moreover, S-MGB-364 inhibited the relaxation of Mtb topoisomerase I but not the human form. In macrophages, S-MGB-364 or S-MGB-364-NIV did not cause DNA damage as shown by the low γ-H2AX expression. Importantly, in the lungs, the intranasal administration of S-MGB-364 or S-MGB-364-NIV formulation in Mtb-infected mice was non-toxic and resulted in a ∼1 log cfu reduction in mycobacterial burden, reduced the expression of proinflammatory cytokines/chemokines, altered immune cell recruitment, and importantly reduced recruitment of neutrophils.

conclusionsTogether, these data provide proof of concept for S-MGBs as novel anti-TB therapeutics in vivo.

Indexed as

Mycobacterium tuberculosisTuberculosisAnimalsAntitubercular AgentsImmunityMacrophagesMiceAntitubercular Agents

Identifiers

PMID35084027
PMCPMC8969509
OpenAlexW4206504757

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.