Evidence map›Paper›PMID 33120116›Full record

ArticleCell host & microbe2021

Exploration of Bacterial Bottlenecks and Streptococcus pneumoniae Pathogenesis by CRISPRi-Seq.

Xue Liu, Jacqueline M Kimmey, Laura Matarazzo, Vincent de Bakker, Laurye Van Maele, Jean-Claude Sirard, Victor Nizet, Jan-Willem Veening

Abstract read
In one paragraph

Article in Cell host & microbe, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
–field-weighted citation impact
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

80 citing papers in PubMed.

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  9. Functional Genomics: Principles and Methods.Advances in experimental medicine and biology · 2026
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20 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

8 authors.

Xue LiuDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, Lausanne 1015, Switzerland.
Jacqueline M KimmeyDivision of Host-Microbe Systems and Therapeutics, Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA, USA.
Laura MatarazzoUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
Vincent de BakkerDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, Lausanne 1015, Switzerland.
Laurye Van MaeleUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
Jean-Claude SirardUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
Victor NizetDivision of Host-Microbe Systems and Therapeutics, Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
Jan-Willem VeeningDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, Lausanne 1015, Switzerland. Electronic address: jan-willem.veening@unil.ch.

Funding

C3-Dependent Intracellular Killing in Innate Immunity and Bacterial PathogenesisR01AI145325 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIZET, VICTOR, RAFFATELLU, MANUELA · 2019 to 2023
$3.1M
NIAID NIH HHS R01 AI145325
6 · The paper itself

Abstract

Streptococcus pneumoniae is an opportunistic human pathogen that causes invasive diseases, including pneumonia, with greater health risks upon influenza A virus (IAV) co-infection. To facilitate pathogenesis studies in vivo, we developed an inducible CRISPR interference system that enables genome-wide fitness testing in one sequencing step (CRISPRi-seq). We applied CRISPRi-seq to assess bottlenecks and identify pneumococcal genes important in a murine pneumonia model. A critical bottleneck occurs at 48 h with few bacteria causing systemic infection. This bottleneck is not present during IAV superinfection, facilitating identification of pneumococcal pathogenesis-related genes. Top in vivo essential genes included purA, encoding adenylsuccinate synthetase, and the cps operon required for capsule production. Surprisingly, CRISPRi-seq indicated no fitness-related role for pneumolysin during superinfection. Interestingly, although metK (encoding S-adenosylmethionine synthetase) was essential in vitro, it was dispensable in vivo. This highlights advantages of CRISPRi-seq over transposon-based genetic screens, as all genes, including essential genes, can be tested for pathogenesis potential.

Indexed as

Genes, BacterialAdenylosuccinate SynthaseAnimalsClustered Regularly Interspaced Short Palindromic RepeatsFemaleGenetic FitnessHigh-Throughput Nucleotide SequencingInfluenza A virusMaleMiceMice, Inbred BALB CMice, Inbred C57BLOperonOrthomyxoviridae InfectionsPneumonia, PneumococcalStreptococcus pneumoniaeAdenylosuccinate Synthasebacterial pathogenesisbottleneckCRISPRi-seqinfluenza A virus superinfectionpneumoniaStreptococcus pneumoniae

Identifiers

PMID33120116
PMCPMC7855995

What OpenQuestion holds

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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.