Evidence map›Paper›PMID 26216418›Full record

ArticleInfection and immunity2015

Acylation Enhances, but Is Not Required for, the Cytotoxic Activity of Mannheimia haemolytica Leukotoxin in Bighorn Sheep.

Sai A Batra, Sudarvili Shanthalingam, Gerhard R Munske, Bindu Raghavan, Abirami Kugadas, Jegarubee Bavanthasivam, Sarah K Highlander, Subramaniam Srikumaran

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-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

5 citing papers in PubMed, 8 citations in OpenAlex.

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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 at 2 institutions in 1 country.

Sai A BatraDepartment of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.
Sudarvili ShanthalingamDepartment of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.
Gerhard R MunskeMolecular Biology and Genomics Core, Washington State University, Pullman, Washington, USA.
Bindu RaghavanDepartment of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.
Abirami KugadasDepartment of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.
Jegarubee BavanthasivamDepartment of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.
Sarah K HighlanderJ. Craig Venter Institute, San Diego, California, USA.
Subramaniam SrikumaranDepartment of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA ssrikumaran@vetmed.wsu.edu.
Washington State University · USJ. Craig Venter Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mannheimia haemolytica causes pneumonia in domestic and wild ruminants. Leukotoxin (Lkt) is the most important virulence factor of the bacterium. It is encoded within the four-gene lktCABD operon: lktA encodes the structural protoxin, and lktC encodes a trans-acylase that adds fatty acid chains to internal lysine residues in the protoxin, which is then secreted from the cell by a type 1 secretion system apparatus encoded by lktB and lktD. It has been reported that LktC-mediated acylation is necessary for the biological effects of the toxin. However, an LktC mutant that we developed previously was only partially attenuated in its virulence for cattle. The objective of this study was to elucidate the role of LktC-mediated acylation in Lkt-induced cytotoxicity. We performed this study in bighorn sheep (Ovis canadensis) (BHS), since they are highly susceptible to M. haemolytica infection. The LktC mutant caused fatal pneumonia in 40% of inoculated BHS. On necropsy, a large number of necrotic polymorphonuclear leukocytes (PMNs) were observed in the lungs. Lkt from the mutant was cytotoxic to BHS PMNs in an in vitro cytotoxicity assay. Flow cytometric analysis of mutant Lkt-treated PMNs revealed the induction of necrosis. Scanning electron microscopic analysis revealed the presence of pores and blebs on mutant-Lkt-treated PMNs. Mass spectrometric analysis confirmed that the mutant secreted an unacylated Lkt. Taken together, these results suggest that acylation is not necessary for the cytotoxic activity of M. haemolytica Lkt but that it enhances the potency of the toxin.

Indexed as

AcylationAnimalsExotoxinsFlow CytometryLungMannheimia haemolyticaNeutrophilsPasteurellosis, PneumonicSheepSheep, BighornSheep DiseasesExotoxinsleukotoxin

Identifiers

PMID26216418
PMCPMC4567630
OpenAlexW1885928832

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Registered trials

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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.