Sanchez, C;
Hinojosa, CA;
Shivshankar, P;
Hyams, C;
Camberlein, E;
Brown, JS;
Orihuela, CJ;
(2011)
Changes in capsular serotype alter the surface exposure of pneumococcal adhesins and impact virulence.
PLoS One
, 6
(10)
, Article e26587. 10.1371/journal.pone.0026587.
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Abstract
We examined the contribution of serotype on Streptococcus pneumoniae adhesion and virulence during respiratory tract infection using a panel of isogenic TIGR4 (serotype 4) mutants expressing the capsule types 6A (+6A), 7F (+7F) and 23F (+23F) as well as a deleted and restored serotype 4 (+4) control strain. Immunoblots, bacterial capture assays with immobilized antibody, and measurement of mean fluorescent intensity by flow cytometry following incubation of bacteria with antibody, all determined that the surface accessibility, but not total protein levels, of the virulence determinants Pneumococcal surface protein A (PspA), Choline binding protein A (CbpA), and Pneumococcal serine-rich repeat protein (PsrP) changed with serotype. In vitro, bacterial adhesion to Detroit 562 pharyngeal or A549 lung epithelial cells was modestly but significantly altered for +6A, +7F and +23F. In a mouse model of nasopharyngeal colonization, the number of +6A, +7F, and +23F pneumococci in the nasopharynx was reduced 10 to 100-fold versus +4; notably, only mice challenged with +4 developed bacteremia. Intratracheal challenge of mice confirmed that capsule switch strains were highly attenuated for virulence. Compared to +4, the +6A, +7F, and +23F strains were rapidly cleared from the lungs and were not detected in the blood. In mice challenged intraperitoneally, a marked reduction in bacterial blood titers was observed for those challenged with +6A and +7F versus +4 and +23F was undetectable. These findings show that serotype impacts the accessibility of surface adhesins and, in particular, affects virulence within the respiratory tract. They highlight the complex interplay between capsule and protein virulence determinants.
| Type: | Article |
|---|---|
| Title: | Changes in capsular serotype alter the surface exposure of pneumococcal adhesins and impact virulence |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0026587 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0026587 |
| Language: | English |
| Additional information: | © 2011 Sanchez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Dr. Sanchez is supported through the United States National Institutes of Health, National Institute of Dental and Craniofacial Research grant DE14318 for the Craniofacial Oral-Biology Student Training in Academic Research (COSTAR) program. Dr. Hinojosa was supported by the Astor Foundation and Glaxo Smith Kline through the University College London, MB, PhD program. Dr. Camberlein was supported by the United Kingdom Medical Research Council. Dr. Orihuela is supported by United States National Institutes of Health, National Institute of Allergy and Infectious Diseases grant AI078972. For work at University College London Hospitals/University College London a proportion of funding was obtained from the United Kingdom Department of Health, National Institute for Health Research Biomedical Research Centre's funding scheme. The University of Texas Health Science Center Flow Cytometry Core Facility is supported by U.S. National Institutes of Health, National Cancer Institute grant CA54174 and UL1 RR025767. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1325606 |
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