Evidence map›Paper›PMID 29709019›Full record

ArticlePLoS pathogens2018

The SecA2 pathway of Mycobacterium tuberculosis exports effectors that work in concert to arrest phagosome and autophagosome maturation.

Katelyn E Zulauf, Jonathan Tabb Sullivan, Miriam Braunstein

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 111 citations in OpenAlex.

  1. Review
  2. Review
  3. HowVaccines · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. TheFrontiers in medicine · 2026
    Article
  9. Screening of Novel Inhibitors Targeting the Non-ATP-binding Domain ofMedicinal chemistry (Shariqah (United Arab Emirates)) · 2026
    Article
  10. Protein-Mediated Virulence in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026
    Review
  11. Secreted proteins ofFrontiers in tuberculosis · 2026
    Review
  12. Article
  13. SMURF2 inhibits autophagic control ofbioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. International journal of molecular sciences · 2025
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review

16 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Katelyn E ZulaufDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Jonathan Tabb SullivanDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.ORCID 0000-0002-5925-4203
Miriam BraunsteinDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.ORCID 0000-0003-1180-0030
University of North Carolina at Chapel Hill · US

Funding

Protein Secretion Pathways of Mycobacterium tuberculosisR01AI054540 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BRAUNSTEIN, MIRIAM S. · 2004 to 2013
$2.7M
NIAID NIH HHS R01 AI054540NIH HHS R01 AI054540
6 · The paper itself

Abstract

To subvert host defenses, Mycobacterium tuberculosis (Mtb) avoids being delivered to degradative phagolysosomes in macrophages by arresting the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. The SecA2 dependent protein export system is required for phagosome maturation arrest and consequently growth of Mtb in macrophages. To better understand the role of the SecA2 pathway in phagosome maturation arrest, we identified two effectors exported by SecA2 that contribute to this process: the phosphatase SapM and the kinase PknG. Then, utilizing the secA2 mutant of Mtb as a platform to study effector functions, we identified specific steps in phagosome maturation inhibited by SapM and/or PknG. By identifying a histidine residue that is essential for SapM phosphatase activity, we confirmed for the first time that the phosphatase activity of SapM is required for its effects on phagosome maturation in macrophages. We further demonstrated that SecA2 export of SapM and PknG contributes to the ability of Mtb to replicate in macrophages. Finally, we extended our understanding of the SecA2 pathway, SapM, and PknG by revealing that their contribution goes beyond preventing Mtb delivery to mature phagolysosomes and includes inhibiting Mtb delivery to autophagolysosomes. Together, our results revealed SapM and PknG to be two effectors exported by the SecA2 pathway of Mtb with distinct as well as cumulative effects on phagosome and autophagosome maturation. Our results further reveal that Mtb must have additional mechanisms of limiting acidification of the phagosome, beyond inhibiting recruitment of the V-ATPase proton pump to the phagosome, and they indicate differences between effects of Mtb on phagosome and autophagosome maturation.

Indexed as

Host-Pathogen InteractionsAdenosine TriphosphatasesAnimalsAutophagosomesAutophagyBacterial ProteinsFemaleLysosomesMacrophagesMembrane Transport ProteinsMiceMice, Inbred C57BLMycobacterium tuberculosisPhagosomesPhosphoric Monoester HydrolasesProtein Serine-Threonine KinasesAdenosine TriphosphatasesBacterial ProteinsMembrane Transport ProteinsPhosphoric Monoester Hydrolasesprotein kinase G, Mycobacterium tuberculosisProtein Serine-Threonine KinasesProton PumpsSecA2 protein, Mycobacterium

Identifiers

PMID29709019
PMCPMC5945054
OpenAlexW2802939794

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.