Evidence map›Paper›PMID 24794568›Full record

ArticleJournal of bacteriology2014

Streptococcus pyogenes polymyxin B-resistant mutants display enhanced ExPortal integrity.

Gary C Port, Luis A Vega, Andrew B Nylander, Michael G Caparon

Open access · bronzeAbstract read
In one paragraph

Article in Journal of bacteriology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.9field-weighted citation impact, top 7% 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

19 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. An energy coupling factor transporter ofbioRxiv : the preprint server for biology · 2024
    Article
  6. Acyl-AcpB, a FabT corepressor inJournal of bacteriology · 2023
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Genetics of Group A Streptococci.Microbiology spectrum · 2019
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Polymyxin: Alternative Mechanisms of Action and Resistance.Cold Spring Harbor perspectives in medicine · 2016
    Review
  17. Article
  18. Article
  19. Article
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

4 authors at 1 institution in 1 country.

Gary C PortDepartment of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Luis A VegaDepartment of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Andrew B NylanderDepartment of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Michael G CaparonDepartment of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, USA caparon@borcim.wustl.edu.
Washington University in St. Louis · US

Funding

PROTEASE AND ROP GENES IN S. PYOGENES VIRULENCER01AI046433 · NIAID · WASHINGTON UNIVERSITY · PI CAPARON, MICHAEL G. · 2000 to 2014
$4.7M
Characterizing Exportal by a Polymyxin B Resistance-Based Mutagenic ApproachF31AI081504 · NIAID · WASHINGTON UNIVERSITY · PI VEGA, LUIS ALBERTO · 2009 to 2010
$56k
NIAID NIH HHS 1F31AI081504NIAID NIH HHS AI046433NIAID NIH HHS F31 AI081504NIAID NIH HHS R01 AI046433
6 · The paper itself

Abstract

The ExPortal protein secretion organelle in Streptococcus pyogenes is an anionic phospholipid-containing membrane microdomain enriched in Sec translocons and postsecretion protein biogenesis factors. Polymyxin B binds to and disrupts ExPortal integrity, resulting in defective secretion of several toxins. To gain insight into factors that influence ExPortal organization, a genetic screen was conducted to select for spontaneous polymyxin B-resistant mutants displaying enhanced ExPortal integrity. Whole-genome resequencing of 25 resistant mutants revealed from one to four mutations per mutant genome clustered primarily within a core set of 10 gene groups. Construction of mutants with individual deletions or insertions demonstrated that 7 core genes confer resistance and enhanced ExPortal integrity through loss of function, while 3 were likely due to gain of function and/or combinatorial effects. Core resistance genes include a transcriptional regulator of lipid biosynthesis, several genes involved in nutrient acquisition, and a variety of genes involved in stress responses. Two members of the latter class also function as novel regulators of the secreted SpeB cysteine protease. Analysis of the most frequently isolated mutation, a single nucleotide deletion in a track of 9 consecutive adenine residues in pstS, encoding a component of a high-affinity Pi transporter, suggests that this sequence functions as a molecular switch to facilitate stress adaptation. Together, these data suggest the existence of a membrane stress response that promotes enhanced ExPortal integrity and resistance to cationic antimicrobial peptides.

Indexed as

Anti-Bacterial AgentsCarbohydrate MetabolismDNA, BacterialDrug Resistance, BacterialGene Expression Regulation, BacterialGenome, BacterialMutationOrganellesPolymyxin BProtein TransportStreptococcus pyogenesStress, PhysiologicalAnti-Bacterial AgentsDNA, BacterialPolymyxin B

Identifiers

PMID24794568
PMCPMC4097577
OpenAlexW2040610264

What OpenQuestion holds

Textmetadata
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.