Absence of Platelet Endothelial Cell Adhesion Molecule 1, PECAM-1/CD31,<i>In Vivo</i>Increases Resistance to Salmonella enterica Serovar Typhimurium in Mice

Lovelace, Michael D.; Yap, May Lin; Yip, Jana; Müller, William A.; Wijburg, Odilia L. C.; Jackson, Denise E.

doi:10.1128/iai.01295-12

Cited by 14 publications

(10 citation statements)

References 45 publications

(52 reference statements)

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“…Salmonella-susceptible C57BL/6 mice and Salmonella-resistant B6.Nramp1 R/R mice were generated by backcrossing the Nramp1 R/R gene from CBA mice onto the C57BL/6 background through 13 backcrosses, followed by brother ϫ sister mating to generate homozygous B6.Nramp R/R mice. The genotype of B6.Nramp1 R/R mice was confirmed using allele-specific single nucleotide polymorphism (SNP) PCR (32). Initial pilot experiments were performed by inoculating five mice of each strain with 3 ϫ 10 3 CFU of a fresh subculture of isolate STm5 (18 h static at 37°C; optical density at 600 nm [OD 600 ] ϭ 0.6) from unpassaged stocks.…”

Section: Methodsmentioning

confidence: 99%

Analysis of Salmonella enterica Serovar Typhimurium Variable-Number Tandem-Repeat Data for Public Health Investigation Based on Measured Mutation Rates and Whole-Genome Sequence Comparisons

et al. 2014

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c Variable-number tandem repeats (VNTRs) mutate rapidly and can be useful markers for genotyping. While multilocus VNTR analysis (MLVA) is increasingly used in the detection and investigation of food-borne outbreaks caused by Salmonella enterica serovar Typhimurium (S. Typhimurium) and other bacterial pathogens, MLVA data analysis usually relies on simple clustering approaches that may lead to incorrect interpretations. Here, we estimated the rates of copy number change at each of the five loci commonly used for S. Typhimurium MLVA, during in vitro and in vivo passage. We found that loci STTR5, STTR6, and STTR10 changed during passage but STTR3 and STTR9 did not. Relative rates of change were consistent across in vitro and in vivo growth and could be accurately estimated from diversity measures of natural variation observed during large outbreaks. Using a set of 203 isolates from a series of linked outbreaks and whole-genome sequencing of 12 representative isolates, we assessed the accuracy and utility of several alternative methods for analyzing and interpreting S. Typhimurium MLVA data. We show that eBURST analysis was accurate and informative. For construction of MLVA-based trees, a novel distance metric, based on the geometric model of VNTR evolution coupled with locus-specific weights, performed better than the commonly used simple or categorical distance metrics. The data suggest that, for the purpose of identifying potential transmission clusters for further investigation, isolates whose profiles differ at one of the rapidly changing STTR5, STTR6, and STTR10 loci should be collapsed into the same cluster.

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Section: Methodsmentioning

confidence: 99%

Analysis of Salmonella enterica Serovar Typhimurium Variable-Number Tandem-Repeat Data for Public Health Investigation Based on Measured Mutation Rates and Whole-Genome Sequence Comparisons

et al. 2014

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“…PECAM 1-deficient mice were more susceptible to LPS than mice with an intact CD31 receptor. Lovelace et al (2013) found that PECAM 1-deficient mice are more resistant to infection with Salmonella typhimurium than wild-type mice. Analogous to the variants on SSC2, the role of PECAM 1 in porcine pleuropneumonia needs to be addressed by further studies.…”

Section: Discussionmentioning

confidence: 99%

Candidate genes and gene markers for the resistance to porcine pleuropneumonia

et al. 2020

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Actinobacillus (A.) pleuropneumoniae is one of the most important respiratory pathogens in global pig production. Antimicrobial treatment and vaccination provide only limited protection, but genetic disease resistance is a very promising alternative for sustainable prophylaxis. Previous studies have discovered multiple QTL that may explain up to 30% of phenotypic variance. Based on these findings, the aim of the present study was to use genomic sequencing to identify genetic markers for resistance to pleuropneumonia in a segregating commercial German Landrace line. 163 pigs were infected with A. pleuropneumoniae Serotype 7 through a standardized aerosol infection method. Phenotypes were accurately defined on a clinical, pathological and microbiological basis. The 58 pigs with the most extreme phenotypes were genotyped by sequencing (next-generation sequencing). SNPs were used in a genome-wide association study. The study identified genome-wide associated SNPs on three chromosomes, two of which were chromosomes of QTL which had been mapped in a recent experiment. Each variant explained up to 20% of the total phenotypic variance. Combined, the three variants explained 52.8% of the variance. The SNPs are located in genes involved in the pathomechanism of pleuropneumonia. This study confirms the genetic background for the host's resistance to pleuropneumonia and indicates a potential role of three candidates on SSC2, SSC12 and SSC15. Favorable gene variants are segregating in commercial populations. Further work is needed to verify the results in a controlled study and to identify the functional QTN.

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“…PECAM-1 Ϫ/Ϫ mice were more resistant to gastrointestinal infection with S. Typhimurium than wild-type mice, resulting in lower bacterial loads in organs such as the liver and the spleen (17). Whole-bacterial-cell enzyme-linked immunosorbent assays revealed that human and murine PECAM-1 can bind to S. Typhimurium, indicating that transmembrane-expressed PE-CAM-1 is capable of binding to bacteria, which may have pathogenic consequences (17). In our study, S. pneumoniae was clearly shown to colocalize with PECAM-1 both in vitro and in vivo, and incubation of S. pneumoniae with endothelial cell lysates enabled PECAM-1 to associate with the bacteria.…”

Section: Figmentioning

confidence: 99%

“…In particular, the involvement of PECAM-1 in leukocyte-endothelium interaction and leukocyte transendothelial migration makes PECAM-1 a key molecule in inflammation and neuroinflammation (15,16). Recently, PECAM-1 was implicated in Salmonella enterica serovar Typhimurium infections (17), which raised the question of whether PECAM-1 also plays a role in host-pneumococcal interactions. Accordingly, the aim of the present study was to investigate whether PECAM-1 plays a role in S. pneumoniae adhesion to the endothelium of the blood-brain barrier.…”

mentioning

confidence: 99%

Platelet Endothelial Cell Adhesion Molecule-1, a Putative Receptor for the Adhesion of Streptococcus pneumoniae to the Vascular Endothelium of the Blood-Brain Barrier

2014

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bThe Gram-positive bacterium Streptococcus pneumoniae is the main causative agent of bacterial meningitis. S. pneumoniae is thought to invade the central nervous system via the bloodstream by crossing the vascular endothelium of the blood-brain barrier. The exact mechanism by which pneumococci cross endothelial cell barriers before meningitis develops is unknown. Here, we investigated the role of PECAM-1/CD31, one of the major endothelial cell adhesion molecules, in S. pneumoniae adhesion to vascular endothelium of the blood-brain barrier. Mice were intravenously infected with pneumococci and sacrificed at various time points to represent stages preceding meningitis. Immunofluorescent analysis of brain tissue of infected mice showed that pneumococci colocalized with PECAM-1. In human brain microvascular endothelial cells (HBMEC) incubated with S. pneumoniae, we observed a clear colocalization between PECAM-1 and pneumococci. Blocking of PECAM-1 reduced the adhesion of S. pneumoniae to endothelial cells in vitro, implying that PECAM-1 is involved in pneumococcal adhesion to the cells. Furthermore, using endothelial cell protein lysates, we demonstrated that S. pneumoniae physically binds to PECAM-1. Moreover, both in vitro and in vivo PECAM-1 colocalizes with the S. pneumoniae adhesion receptor pIgR. Lastly, immunoprecipitation experiments revealed that PECAM-1 can physically interact with pIgR. In summary, we show for the first time that blood-borne S. pneumoniae colocalizes with PECAM-1 expressed by brain microvascular endothelium and that, in addition, they colocalize with pIgR. We hypothesize that this interaction plays a role in pneumococcal binding to the blood-brain barrier vasculature prior to invasion into the brain.

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Absence of Platelet Endothelial Cell Adhesion Molecule 1, PECAM-1/CD31,In VivoIncreases Resistance to Salmonella enterica Serovar Typhimurium in Mice

Cited by 14 publications

References 45 publications

Analysis of Salmonella enterica Serovar Typhimurium Variable-Number Tandem-Repeat Data for Public Health Investigation Based on Measured Mutation Rates and Whole-Genome Sequence Comparisons

Analysis of Salmonella enterica Serovar Typhimurium Variable-Number Tandem-Repeat Data for Public Health Investigation Based on Measured Mutation Rates and Whole-Genome Sequence Comparisons

Candidate genes and gene markers for the resistance to porcine pleuropneumonia

Platelet Endothelial Cell Adhesion Molecule-1, a Putative Receptor for the Adhesion of Streptococcus pneumoniae to the Vascular Endothelium of the Blood-Brain Barrier

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