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EuroPneumo Special Issue / pneumonia 2015 Oct 21;7:I–72 O5.5 Conserved Streptococcus pneumoniae spirosomes point toward a single type of transformation pilus in competence Petya V. Krasteva 1, 2 , Raphael Laurenceau 1, 2 , Amy Diallo 1, 2 , Sahra Ouarti 1, 2 , Magalie Duchateau 1, 2 , Christian Malosse 1, 2 , Julia Chamot-Rooke 1, 2 , Remi Fronzes 1, 2 1 Institut Pasteur, Paris, France; 2 CNRS UMR3528, Paris, France The success of Streptococcus pneumoniae as a major human pathogen is largely due to its remarkable genomic plasticity, allowing efficient escape from antimicrobials action and host immune response. Natural transformation, or the active uptake and chromosomal integration of exogenous DNA during the transitory differentiated state competence, is the main mechanism for horizontal gene transfer and genomic makeover in pneumococci. DNA uptake requires expression of a transformation pilus but 2 markedly different models for pilus assembly and function have been proposed. We previously reported a long, Type 4 pilus-like appendage on the surface of competent pneumococci that likely binds extracellular DNA as initial receptor, while a separate study proposed that secreted short, ‘plaited’ transformation pili act simply as peptidoglycan drills to open DNA gateways. Here we show that the ‘plaited’ structures are not competencespecific or related to transformation. We further demonstrate that these are macromolecular assemblies of the metabolic enzyme acetaldehyde-alcohol dehydrogenase—or spirosomes—broadly conserved across the bacterial kingdom. O6.1 Pathogenesis of non-encapsulated Streptococcus pneumoniae in experimental otitis media Larry McDaniel University of Mississippi Medical Center, Jackson, MS, USA Otitis media (OM) is the most common reason for paediatrician visits and can result in hearing loss. Streptococcus pneumoniae (pneumococcus) remains an important cause of OM. The diverse pneumococcal polysaccharide capsule types have long been thought to be necessary for colonisation and disease. With the increase use of pneumococcal conjugate vaccines (PCVs), there have been increased reports of pneumococcal disease caused by nonencapsulated S. pneumoniae (NESp). We have previously demonstrated that pneumococcal surface protein K (PspK) replaces the capsule locus of some NESp isolates and plays a role in virulence. Additional NESp have been identified in which the cps genes have been replaced by genes encoding AliC and AliD. Understanding how NESp are able to cause infections is important because current pneumococcal vaccines are only effective against encapsulated strains. Thus, the purpose of this study was to further evaluate the role of these NESp proteins in virulence. We used a murine colonisation model and a chinchilla model of OM for in vivo studies. In addition to pathology, pneumococcal burden was determined in each model. Human epithelial cell lines were utilised to assess NESp adhesion and invasion. In vitro assays examining biofilm production and viability were also performed. Significant differences in epithelial cell adhesion and invasion were strain dependent. An increase in in vitro biofilm viability and production was observed in deletion mutants. We also demonstrated that PspK, AliC, and AliD enhanced murine nasopharyngeal colonisation and were required for OM in the chinchilla. Historically, NESp have been considered to be comparatively avirulent. We have demonstrated that virulence of NESp is increased as a result of PspK, AliC, and AliD. Further study of this disease causing pneumococcal population is essential. pneumonia 2015 Volume 7 59
EuroPneumo Special Issue / pneumonia 2015 Oct 21;7:I–72 O6.2 Modulation of nasopharyngeal innate defences by viral co-infection predisposes individuals to experimental pneumococcal carriage Sarah Glennie 1, 6 , Jenna F Gritzfeld 1 , Shaun H Pennington 1 , Michael Garner-Jones 1 , Nicholas Coombes 1 , Mark J Hopkins 2 , Cintia F Vadesilho 3 , Eliane N Miyaji 3 , Duolao Wang 4 , Angela D Wright 5 , Andrea M Collins 5 , Stephen B Gordon 1 , Daniela M Ferreira 1 1 Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK; 2 Liverpool Specialist Virology Centre, Royal Liverpool and Broadgreen University Hospital, Liverpool, UK; 3 Centro de Biotecnologia, Instituto Butantan, Sao Paulo, Brazil; 4 Tropical Clinical Trial Unit, Liverpool School of Tropical Medicine, Liverpool, UK; 5 NIHR Royal Liverpool and Broadgreen University Hospital NHS Trust, Liverpool, UK; 6 School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK Secondary pneumococcal pneumonia is a major cause of mortality during pandemic influenza. Increased nasopharyngeal colonisation density has been associated with pneumonia. We used an experimental human pneumococcal carriage model to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. One hundred and one healthy subjects were screened for respiratory virus prior to pneumococcal intranasal challenge. Virus was associated with increased likelihood of colonisation (75% virus positive became colonised versus 46% virus negative subjects; p = 0.02). Nasal Factor H (FH) levels were increased in virus positive subjects and were associated with increased colonisation density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of co-infection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonisation especially in those with underlying viral infection. We will now evaluate the effect of the live attenuated influenza vaccine on pneumococcal carriage susceptibility and carriage density as well as the immunological mechanisms involved. Acknowledgments: Bill and Melinda Gates Foundation, National Institute for Health Research (NIHR) Local Comprehensive Research Network, and the Medical Research Council/Sao Paulo Research Foundation (FAPESP). O6.3 Circulating pneumolysin is a potent inducer of cardiac injury during pneumococcal infection Daniel Neill, Yasir Alhamdi, Simon Abrams, Hesham Malak, Richard Barrett-Jolley, Gouzheng Wang, Cheng-Hock Toh, Aras Kadioglu University of Liverpool, Liverpool, UK Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis, and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wildtype PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), which are well-recognized biomarkers of cardiac injury, which was significantly attenuated by PLY-sequestering liposomes. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts and levels were significantly higher in non-surviving than in surviving mice. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins suggesting that the membrane-binding and pore-forming activities of circulating PLY are essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive pneumonia 2015 Volume 7 60
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