Evidence map›Paper›PMID 34724815›Full record

ArticlemBio2021

High-Throughput Mutagenesis and Cross-Complementation Experiments Reveal Substrate Preference and Critical Residues of the Capsule Transporters in

Wan-Zhen Chua, Matthias Maiwald, Kean Lee Chew, Raymond Tzer-Pin Lin, Sanduo Zheng, Lok-To Sham

Open access · goldAbstract read
In one paragraph

Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

14 citing papers in PubMed, 19 citations in OpenAlex.

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  13. Mechanistic insights into the regulation of cell wall hydrolysis by FtsEX and EnvC at the bacterial division site.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  14. Influence of glycan structure on the colonization ofProceedings of the National Academy of Sciences of the United States of America · 2023
    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

6 authors at 4 institutions in 2 countries.

Wan-Zhen ChuaInfectious Diseases Translational Research Programme and Department of Microbiology and Immunology, National University of Singaporegrid.4280.e, Singapore.ORCID 0000-0001-9714-8463
Matthias MaiwaldInfectious Diseases Translational Research Programme and Department of Microbiology and Immunology, National University of Singaporegrid.4280.e, Singapore.ORCID 0000-0001-5448-8417
Kean Lee ChewDepartment of Laboratory Medicine, National University Hospitalgrid.412106.0, Singapore.
Raymond Tzer-Pin LinInfectious Diseases Translational Research Programme and Department of Microbiology and Immunology, National University of Singaporegrid.4280.e, Singapore.
Sanduo ZhengNational Institute of Biological Sciences, Beijing, China.ORCID 0000-0002-7784-0177
Lok-To ShamInfectious Diseases Translational Research Programme and Department of Microbiology and Immunology, National University of Singaporegrid.4280.e, Singapore.ORCID 0000-0001-9047-0310
National University of Singapore · SGMinistry of Health · SGNational Institute of Biological Sciences, Beijing · CNNational University Hospital · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MOP (Multidrug/Oligosaccharidyl-lipid/Polysaccharide) family transporters are found in almost all life forms. They are responsible for transporting lipid-linked precursors across the cell membrane to support the synthesis of various glycoconjugates. While significant progress has been made in elucidating their transport mechanism, how these transporters select their substrates remains unclear. Here, we systematically tested the MOP transporters in the Streptococcus pneumoniae capsule pathway for their ability to translocate noncognate capsule precursors. Sequence similarity cannot predict whether these transporters are interchangeable. We showed that subtle changes in the central aqueous cavity of the transporter are sufficient to accommodate a different cargo. These changes can occur naturally, suggesting a potential mechanism of expanding substrate selectivity. A directed evolution experiment was performed to identify gain-of-function variants that translocate a noncognate cargo. Coupled with a high-throughput mutagenesis and sequencing (Mut-seq) experiment, residues that are functionally important for the capsule transporter were revealed. Lastly, we showed that the expression of a flippase that can transport unfinished precursors resulted in an increased susceptibility to bacitracin and mild cell shape defects, which may be a driving force to maintain transporter specificity.

Indexed as

MutagenesisAmino Acid MotifsBacterial CapsulesBacterial ProteinsGenetic Complementation TestHigh-Throughput Nucleotide SequencingMembrane Transport ProteinsStreptococcus pneumoniaeBacterial ProteinsMembrane Transport Proteinscapsular polysaccharidecapsulelipid flippaseMOP transportersStreptococcus pneumoniaetransporters

Identifiers

PMID34724815
PMCPMC8561386
OpenAlexW3209941303

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.