Abdullahi, O. et al. The prevalence and risk factors for pneumococcal colonization of the nasopharynx among children in Kilifi District, Kenya. PLoS ONE 7, e30787 (2012).
Yahiaoui, R. Y. et al. Prevalence and antibiotic resistance of commensal Streptococcus pneumoniae in nine European countries. Future Microbiol. 11, 737–744 (2016).
Bogaert, D., De Groot, R. & Hermans, P. W. Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect. Dis. 4, 144–154 (2004).
Whitney, C. G. et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N. Engl. J. Med. 348, 1737–1746 (2003).
Musher, D. How contagious are common respiratory tract infections? N. Engl. J. Med. 348, 1256–1266 (2003).
Numminen, E. et al. Climate induces seasonality in pneumococcal transmission. Sci. Rep. 5, 11344 (2015).
Gwaltney, J. J., Sande, M., Austrian, R. & Hendley, J. Spread of Streptococcus pneumoniae in families. II. Relation of transfer of S. pneumoniae to incidence of colds and serum antibody. J. Infect. Dis. 132, 62–68 (1975).
McCullers, J. et al. Influenza enhances susceptibility to natural acquisition of and disease due to Streptococcus pneumoniae in ferrets. J. Infect. Dis. 202, 1287–1295 (2010).
Diavatopoulos, D. A. et al. Influenza A virus facilitates Streptococcus pneumoniae and disease. FASEB. J. 24, 1789–1798 (2010). This study demonstrates the role of influenza virus in pneumococcal transmission in an infant mouse model.
Barbier, D. et al. Influenza A induces the major secreted airway mucin MUC5AC in a protease-EGFR-extracellular regulated kinase-Sp1-dependent pathway. Am. J. Respir. Cell. Mol. Biol. 47, 149–157 (2012).
Siegel, S., Roche, A. & Weiser, J. Influenza promotes pneumococcal growth during coinfection by providing host sialylated substrates as a nutrient source. Cell Host Microbe 16, 55–67 (2014).
Richard, A. L., Siegel, S. J., Erikson, J. & Weiser, J. N. TLR2 signaling decreases transmission of Streptococcus pneumoniae by limiting bacterial shedding in an infant mouse Influenza A co-infection model. PLoS Pathog. 10, e1004339 (2014).
Kono, M. et al. Single cell bottlenecks in the pathogenesis of Streptococcus pneumoniae. PLoS Pathog. 12, e1005887 (2016).
Zafar, M. A., Kono, M., Wang, Y., Zangari, T. & Weiser, J. N. Infant mouse model for the study of shedding and transmission during Streptococcus pneumoniae monoinfection. Infect. Immun. 84, 2714–2722 (2016).
Rodrigues, F. et al. Relationships between rhinitis symptoms, respiratory viral infections and nasopharyngeal colonization with Streptococcus pneumoniae. Haemophilus influenza and Staphylococcus aureus in children attending daycare. Pediatr. Infect. Dis. J. 32, 227–232 (2013).
Zafar, M. A., Wang, Y., Hamaguchi, S. & Weiser, J. N. Host-to-host transmission of Streptococcus pneumoniae is driven by its inflammatory toxin, pneumolysin. Cell Host Microbe 21, 73–83 (2017). This study provides evidence that the toxin Ply promotes mucosal inflammation, which facilitates pneumococcal transmission in infant mice.
Matthias, K. A., Roche, A. M., Standish, A. J., Shchepetov, M. & Weiser, J. N. Neutrophil-toxin interactions promote antigen delivery and mucosal clearance of Streptococcus pneumoniae. J. Immunol. 180, 6246–6254 (2008).
Lipsitch, M. & Moxon, E. R. Virulence and transmissibility of pathogens: what is the relationship? Trends Microbiol. 5, 31–37 (1997).
Zafar, M. A., Hamaguchi, S., Zangari, T., Cammer, M. & Weiser, J. N. Capsule type and amount affect shedding and transmission of Streptococcus pneumoniae. mBio 8, e00989–17 (2017).
Marks, L. R., Reddinger, R. M. & Hakansson, A. P. Biofilm formation enhances fomite survival of Streptococcus pneumoniae and Streptococcus pyogenes. Infect. Immun. 82, 1141–1146 (2014).
Verhagen, L. M. et al. Genome-wide identification of genes essential for the survival of Streptococcus pneumoniae in human saliva. PLoS. ONE. 9, e89541 (2014).
Hamaguchi, S., Zafar, M. A., Cammer, M. & Weiser, J. N. Capsule prolongs survival of Streptococcus pneumoniae during starvation. Infect. Immun. https://doi.org/10.1128/IAI.00802-17 (2018).
Walsh, R. L. & Camilli, A. Streptococcus pneumoniae is desiccation tolerant and infectious upon rehydration. mBio 2, e00092–11 (2011).
Zangari, T., Wang, Y. & Weiser, J. N. Streptococcus pneumoniae transmission is blocked by type-specific immunity in an infant mouse model. mBio 8, e00188–17 (2017).
Roche, A. M., Richard, A. L., Rahkola, J. T., Janoff, E. N. & Weiser, J. N. Antibody blocks acquisition of bacterial colonization through agglutination. Mucosal Immunol. 8, 176–185 (2015).
Janoff, E. N. et al. Pneumococcal IgA1 protease subverts specific protection by human IgA1. Mucosal Immunol. 7, 249–256 (2014).
Pennington, S. H. et al. Polysaccharide-specific memory b cells predict protection against experimental human pneumococcal carriage. Am. J. Respir. Crit. Care Med. 194, 1523–1531 (2016).
Mitsi, E. et al. Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriage. Mucosal Immunol. 10, 385–394 (2017). This study shows that the agglutinating activity of anticapsular antibody mediates protection from experimental pneumococcal carriage in humans.
Lemon, J. K. & Weiser, J. N. Degradation products of the extracellular pathogen Streptococcus pneumoniae access the cytosol via its pore-forming toxin. mBio 6, e02110–e02114 (2015).
Davis, K., Nakamura, S. & Weiser, J. Nod2 sensing of lysozyme-digested peptidoglycan promotes macrophage recruitment and clearance of S. pneumoniae colonization in mice. J. Clin. Invest. 121, 3666–3676 (2011).
Karmakar, M. et al. Neutrophil IL-1beta processing induced by pneumolysin is mediated by the NLRP3/ASC inflammasome and caspase-1 activation and is dependent on K+ efflux. J. Immunol. 194, 1763–1775 (2015).
Parker, D. et al. Streptococcus pneumoniae DNA initiates type I interferon signaling in the respiratory tract. mBio 2, e00016–11 (2011).
Davis, K., Akinbi, H., Standish, A. & Weiser, J. Resistance to mucosal lysozyme compensates for the fitness deficit of peptidoglycan modifications by Streptococcus pneumoniae. PLoS Pathog. 4, e1000241 (2008).
Rose, M. C. & Voynow, J. A. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol. Rev. 86, 245–278 (2006).
Feldman, C. et al. The interaction of Streptococcus pneumoniae with intact human respiratory mucosa in vitro. Eur. Respir. J. 5, 576–583 (1992).
Nelson, A. L. et al. Capsule enhances pneumococcal colonization by limiting mucus-mediated clearance. Infect. Immun. 75, 83–90 (2007).
Holmes, A. R. et al. The pavA gene of Streptococcus pneumoniae encodes a fibronectin-binding protein that is essential for virulence. Mol. Microbiol. 41, 1395–1408 (2001).
Bergmann, S., Rohde, M., Chhatwal, G. S. & Hammerschmidt, S. α-Enolase of Streptococcus pneumoniae is a plasmin(ogen)-binding protein displayed on the bacterial cell surface. Mol. Microbiol. 40, 1273–1287 (2001).
Jensch, I. et al. PavB is a surface-exposed adhesin of Streptococcus pneumoniae contributing to nasopharyngeal colonization and airways infections. Mol. Microbiol. 77, 22–43 (2010).
Cundell, D. R., Gerard, N. P., Gerard, C., Idanpaan-Heikkila, I. & Tuomanen, E. I. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377, 435–438 (1995).
Zhang, J. R. et al. The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Cell 102, 827–837 (2000).
Hauck, C. R. Cell adhesion receptors - signaling capacity and exploitation by bacterial pathogens. Med. Microbiol. Immunol. 191, 55–62 (2002).
Kc, R., Shukla, S. D., Walters, E. H. & O’Toole, R. F. Temporal upregulation of host surface receptors provides a window of opportunity for bacterial adhesion and disease. Microbiology 163, 421–430 (2017).
Cron, L. E. et al. Surface-associated lipoprotein PpmA of Streptococcus pneumoniae is involved in colonization in a strain-specific manner. Microbiology 155, 2401–2410 (2009).
Hermans, P. W. et al. The streptococcal lipoprotein rotamase A (SlrA) is a functional peptidyl-prolyl isomerase involved in pneumococcal colonization. J. Biol. Chem. 281, 968–976 (2006).
Gutierrez-Fernandez, J. et al. Modular architecture and unique teichoic acid recognition features of choline-binding protein L (CbpL) contributing to pneumococcal pathogenesis. Sci. Rep. 6, 38094 (2016).
King, S. J. Pneumococcal modification of host sugars: a major contributor to colonization of the human airway? Mol. Oral Microbiol. 25, 15–24 (2010).
Uchiyama, S. et al. The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion. J. Exp. Med. 206, 1845–1852 (2009).
Limoli, D. H., Sladek, J. A., Fuller, L. A., Singh, A. K. & King, S. J. BgaA acts as an adhesin to mediate attachment of some pneumococcal strains to human epithelial cells. Microbiology 157, 2369–2381 (2011).
Andersson, B. et al. Identification of an active dissaccharide unit of a glycoconjugate receptor for pneumococci attaching to human pharyngeal epithelial cells. J. Exp. Med. 158, 559–570 (1983).
Krivan, H. C., Roberts, D. D. & Ginsberg, V. Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAcb1-4 Gal found in some glycolipids. Proc. Natl. Acad. Sci. USA 85, 6157–6161 (1988).
Shak, J. R., Vidal, J. E. & Klugman, K. P. Influence of bacterial interactions on pneumococcal colonization of the nasopharynx. Trends. Microbiol. 21, 129–135 (2013).
Lysenko, E. S. et al. Nod1-signaling overcomes resistance of Streptococcus pneumoniae to opsonophagocytic killing. PLoS Pathog. 3, 1073–1081 (2007). This study elucidates how H. influenzae signalling via NOD1 enhances neutrophil killing of S. pneumoniae, leading to bacterial clearance.
Cremers, A. J. et al. The adult nasopharyngeal microbiome as a determinant of pneumococcal acquisition. Microbiome 2, 44 (2014).
Biesbroek, G. et al. Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am. J. Respir. Crit. Care Med. 190, 1283–1292 (2014).
Miller, E. L., Abrudan, M. I., Roberts, I. S. & Rozen, D. E. Diverse ecological strategies are encoded by Streptococcus pneumoniae bacteriocin-like peptides. Genome Biol. Evol. 8, 1072–1090 (2016).
Dawid, S., Roche, A. & Weiser, J. The blp bacteriocins of Streptococcus pneumoniae mediate intraspecies competition both in vitro and in vivo. Infect. Immun. 75, 443–451 (2007).
Bogaardt, C., van Tonder, A. J. & Brueggemann, A. B. Genomic analyses of pneumococci reveal a wide diversity of bacteriocins — including pneumocyclicin, a novel circular bacteriocin. BMC Genom. 16, 554 (2015).
Nakamura, S., Davis, K. & Weiser, J. Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice. J. Clin. Invest. 121, 3657–3665 (2011). This study demonstrates a mechanism by which concurrent influenza virus infection leads to increased pneumococcal carriage.
McCullers, J. A. & Rehg, J. E. Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor. J. Infect. Dis. 186, 341–350 (2002).
Avadhanula, V. et al. Respiratory viruses augment the adhesion of bacterial pathogens to respiratory epithelium in a viral species- and cell type-dependent manner. J. Virol. 80, 1629–1636 (2006).
Mina, M. J., McCullers, J. A. & Klugman, K. P. Live attenuated influenza vaccine enhances colonization of Streptococcus pneumoniae and Staphylococcus aureus in mice. mBio 5, e01040–13 (2014).
Mina, M. J. Generalized herd effects and vaccine evaluation: impact of live influenza vaccine on off-target bacterial colonisation. J. Infect. 74, (Suppl. 1), S101–s107 (2017).
Thors, V. et al. The effects of live attenuated influenza vaccine on nasopharyngeal bacteria in healthy 2 to 4 year olds. A randomized controlled trial. Am. J. Respir. Crit. Care Med. 193, 1401–1409 (2016).
McCullers, J. The co-pathogenesis of influenza viruses with bacteria in the lung. Nat. Rev. Microbiol. 12, 252–262 (2014). Provides a good overview of how influenza virus co-infection leads to bacterial superinfection in the lungs.
Lees, J. A. et al. Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration. eLife 6, e26255 (2017).
Kadioglu, A., Weiser, J., Paton, J. & Andrew, P. The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat. Rev. Microbiol. 6, 288–301 (2008).
Jochems, S. P. et al. Novel analysis of immune cells from nasal microbiopsy demonstrates reliable, reproducible data for immune populations, and superior cytokine detection compared to nasal wash. PLoS ONE 12, e0169805 (2017).
Zhang, Z., Clarke, T. & Weiser, J. Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J. Clin. Invest. 119, 1899–1909 (2009). This study shows that IL-17A by CD4
+ T cells is required for the recruitment of monocytes and macrophages and effective pneumococcal clearance in unimmunized mice.
Siegel, S., Tamashiro & Weiser, J. Clearance of pneumococcal colonization in infants is delayed through altered macrophage trafficking. PLoS Pathog. 11, e1005004 (2015).
Puchta, A. et al. TNF drives monocyte dysfunction with age and results in impaired anti-pneumococcal immunity. PLoS. Pathog 12, e1005368 (2016).
Malley, R. et al. Antibody-independent, interleukin-17A-mediated, cross-serotype immunity to pneumococci in mice immunized intranasally with the cell wall polysaccharide. Infect. Immun. 74, 2187–2195 (2006).
van Rossum, A., Lysenko, E. & Weiser, J. Host and bacterial factors contributing to the clearance of colonization by Streptococcus pneumoniae in a murine model. Infect. Immun. 73, 7718–7726 (2005).
McCool, T. L., Cate, T. R., Moy, G. & Weiser, J. N. The immune response to pneumococcal proteins during experimental human carriage. J. Exp. Med. 195, 359–365 (2002).
Ferreira, D. M. et al. Controlled human infection and rechallenge with Streptococcus pneumoniae reveals the protective efficacy of carriage in healthy adults. Am. J. Respir. Crit. Care. Med. 187, 855–864 (2013). This study uses a human infection model to demonstrate that immunity induced by a previous colonization episode protects against reacquisition.
Holmlund, E. et al. Antibodies to pneumococcal proteins PhtD, CbpA, and LytC in Filipino pregnant women and their infants in relation to pneumococcal carriage. Clin. Vaccine Immunol. 16, 916–923 (2009).
Jackson, L. A. et al. Effectiveness of pneumococcal polysaccharide vaccine in older adults. N. Engl. J. Med. 348, 1747–1755 (2003).
Richards, L., Ferreira, D. M., Miyaji, E. N., Andrew, P. W. & Kadioglu, A. The immunising effect of pneumococcal nasopharyngeal colonisation; protection against future colonisation and fatal invasive disease. Immunobiology 215, 251–263 (2010).
Cohen, J. M., Wilson, R., Shah, P., Baxendale, H. E. & Brown, J. S. Lack of cross-protection against invasive pneumonia caused by heterologous strains following murine Streptococcus pneumoniae nasopharyngeal colonisation despite whole cell ELISAs showing significant cross-reactive IgG. Vaccine 31, 2328–2332 (2013).
Wright, A. K. et al. Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung. PLoS Pathog. 9, e1003274 (2013).
Wright, A. K. et al. Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage. PLoS. Pathog. 8, e1002622 (2012).
Malley, R. et al. CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization. Proc. Natl Acad. Sci. USA. 102, 4848–4853 (2005).
Trzcinski, K. et al. Protection against nasopharyngeal colonization by Streptococcus pneumoniae is mediated by antigen-specific CD4+ T cells. Infect. Immun. 76, 2678–2684 (2008).
Mubarak, A. et al. A dynamic relationship between mucosal T helper type 17 and regulatory T-cell populations in nasopharynx evolves with age and associates with the clearance of pneumococcal carriage in humans. Clin. Microbiol. Infect. 22, 736.e1–736.e7 (2016).
Polissi, A. et al. Large-scale identification of virulence genes from Streptococcus pneumoniae. Infect. Immun. 66, 5620–5629 (1998).
Lau, G. W. et al. A functional genomic analysis of type 3 Streptococcus pneumoniae virulence. Mol. Microbiol. 40, 555–571 (2001).
Hava, D. L. & Camilli, A. Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol. Microbiol. 45, 1389–1406 (2002).
Orihuela, C. J. et al. Microarray analysis of pneumococcal gene expression during invasive disease. Infect. Immun. 72, 5582–5596 (2004).
Ogunniyi, A. D. et al. Identification of genes that contribute to the pathogenesis of invasive pneumococcal disease by in vitro transcriptomic analysis. Infect. Immun. 80, 3268–3278 (2012).
Honsa, E. S., Johnson, M. D. & Rosch, J. W. The roles of transition metals in the physiology and pathogenesis of Streptococcus pneumoniae. Front. Cell. Infect. Microbiol. 3, 92 (2013).
Brown, J. S., Gilliland, S. M. & Holden, D. W. A. Streptococcus pneumoniae pathogenicity island encoding an ABC transporter involved in iron uptake and virulence. Mol. Microbiol. 40, 572–585 (2001).
McAllister, L. J. et al. Molecular analysis of the psa permease complex of Streptococcus pneumoniae. Mol. Microbiol. 53, 889–901 (2004).
Plumptre, C. D. et al. AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in. Streptococcus pneumoniae. Mol. Microbiol. 91, 834–851 (2014).
Bajaj, M. et al. Discovery of novel pneumococcal surface antigen A (PsaA) inhibitors using a fragment-based drug design approach. ACS Chem. Biol. 10, 1511–1520 (2015).
McDevitt, C. A. et al. A molecular mechanism for bacterial susceptibility to zinc. PLoS Pathog. 7, e1002357 (2011).
Counago, R. M. et al. Imperfect coordination chemistry facilitates metal ion release in the Psa permease. Nat. Chem. Biol. 10, 35–41 (2014).
Kumar, S., Awasthi, S., Jain, A. & Srivastava, R. C. Blood zinc levels in children hospitalized with severe pneumonia: a case control study. Indian Pediatr. 41, 486–491 (2004).
Coles, C. L. et al. Zinc modifies the association between nasopharyngeal Streptococcus pneumoniae carriage and risk of acute lower respiratory infection among young children in rural Nepal. J. Nutr. 138, 2462–2467 (2008).
Hakansson, A. et al. Characterization of binding of human lactoferrin to pneumococcal surface protein A. Infect. Immun. 69, 3372–3381 (2001).
Mirza, S. et al. The effects of differences in pspA alleles and capsular types on the resistance of Streptococcus pneumoniae to killing by apolactoferrin. Microb. Pathog. 99, 209–219 (2016).
Bidossi, A. et al. A functional genomics approach to establish the complement of carbohydrate transporters in Streptococcus pneumoniae. PLoS ONE 7, e33320 (2012).
Buckwalter, C. M. & King, S. J. Pneumococcal carbohydrate transport: food for thought. Trends Microbiol. 20, 517–522 (2012).
King, S. J., Hippe, K. R. & Weiser, J. N. Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniae. Mol. Microbiol. 59, 961–974 (2006).
Robb, M. et al. Molecular characterization of N-glycan degradation and transport in Streptococcus pneumoniae and its contribution to virulence. PLoS Pathog.
13, e1006090 (2017).
Trappetti, C. et al. Autoinducer 2 signaling via the phosphotransferase frua drives galactose utilization by Streptococcus pneumoniae, resulting in hypervirulence. mBio 8, e02269–16 (2017). This study was the first to identify an AI-2 receptor in Gram-positive bacteria and describe a mechanism whereby quorum sensing of AI-2 promotes invasive disease.
Hatcher, B. L., Hale, J. Y. & Briles, D. E. Free sialic acid acts as a signal that promotes Streptococcus pneumoniae invasion of nasal tissue and nonhematogenous invasion of the central nervous system. Infect. Immun. 84, 2607–2615 (2016).
Hentrich, K. et al. Streptococcus pneumoniae senses a human-like sialic acid profile via the response regulator ciaR. Cell Host Microbe 20, 307–317 (2016).
Gratz, N. et al. Pneumococcal neuraminidase activates TGF-beta signalling. Microbiology 163, 1198–1207 (2017).
Hall-Stoodley, L. et al. Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. JAMA 296, 202–211 (2006).
Weimer, K. E. et al. Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease. J. Infect. Dis. 202, 1068–1075 (2010).
Trappetti, C., Ogunniyi, A. D., Oggioni, M. R. & Paton, J. C. Extracellular matrix formation enhances the ability of Streptococcus pneumoniae to cause invasive disease. PLoS ONE 6, e19844 (2011).
Blanchette, K. A. et al. Neuraminidase A-exposed galactose promotes Streptococcus pneumoniae biofilm formation during colonization. Infect. Immun. 84, 2922–2932 (2016).
Sanchez, C. J. et al. The pneumococcal serine-rich repeat protein is an intra-species bacterial adhesin that promotes bacterial aggregation in vivo and in biofilms. PLoS. Pathog 6, e1001044 (2010).
Rose, L. et al. Antibodies against PsrP, a novel Streptococcus pneumoniae adhesin, block adhesion and protect mice against pneumococcal challenge. J. Infect. Dis. 198, 375–383 (2008).
Kim, J. O. & Weiser, J. N. Association of intrastrain phase variation in quantity of capsular polysaccharide and teichoic acid with the virulence of Streptococcus pneumoniae. J. Infect. Dis. 177, 368–377 (1998).
Manso, A. S. et al. A random six-phase switch regulates pneumococcal virulence via global epigenetic changes. Nat. Commun. 5, 5055 (2014). This study elucidates the mechanism underlying the phenomenon of colony opacity phase variation in S. pneumoniae.
Trappetti, C., Potter, A. J., Paton, A. W., Oggioni, M. R. & Paton, J. C. LuxS mediates iron-dependent biofilm formation, competence, and fratricide in Streptococcus pneumoniae. Infect. Immun. 79, 4550–4558 (2011).
Orihuela, C. J. et al. Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. J. Clin. Invest. 119, 1638–1646 (2009).
Brown, A. O. et al. Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function. PLoS Pathog. 10, e1004383 (2014).
Iovino, F. et al. pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion. J. Exp. Med. 214, 1619–1630 (2017).
van Ginkel, F. W. et al. Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection. Proc. Natl. Acad. Sci. USA 100, 14363–14367 (2003).
Talbot, U. M., Paton, A. W. & Paton, J. C. Uptake of Streptococcus pneumoniae by respiratory epithelial cells. Infect. Immun. 64, 3772–3777 (1996).
Hammerschmidt, S. et al. Illustration of pneumococcal polysaccharide capsule during adherence and invasion of epithelial cells. Infect. Immun. 73, 4653–4667 (2005).
Kietzman, C. C., Gao, G., Mann, B., Myers, L. & Tuomanen, E. I. Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium. Nat. Commun. 7, 10859 (2016).
Mitchell, T. J. & Dalziel, C. E. The biology of pneumolysin. Subcell. Biochem. 80, 145–160 (2014).
Rayner, C. F. et al. Interaction of pneumolysin-sufficient and -deficient isogenic variants of Streptococcus pneumoniae with human respiratory mucosa. Infect. Immun. 63, 442–447 (1995).
Mahdi, L. K., Wang, H., Van der Hoek, M. B., Paton, J. C. & Ogunniyi, A. D. Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice. J. Clin. Invest. 122, 2208–2220 (2012).
Berry, A. M. & Paton, J. C. Additive attenuation of virulence of Streptococcus pneumoniae by mutation of the genes encoding pneumolysin and other putative pneumococcal virulence proteins. Infect. Immun. 68, 133–140 (2000).
Chiavolini, D. et al. The three extra-cellular zinc metalloproteinases of Streptococcus pneumoniae have a different impact on virulence in mice. BMC Microbiol. 3, 14 (2003).
Attali, C., Durmort, C., Vernet, T. & Di Guilmi, A. M. The interaction of Streptococcus pneumoniae with plasmin mediates transmigration across endothelial and epithelial monolayers by intercellular junction cleavage. Infect. Immun. 76, 5350–5356 (2008).
Bergmann, S., Rohde, M., Preissner, K. T. & Hammerschmidt, S. The nine residue plasminogen-binding motif of the pneumococcal enolase is the major cofactor of plasmin-mediated degradation of extracellular matrix, dissolution of fibrin and transmigration. Thromb. Haemostasis 94, 304–311 (2005).
Standish, A. & Weiser, J. Human neutrophils kill Streptococcus pneumoniae via serine proteases. J. Immunol. 183, 2602–2609 (2009).
Hergott, C. B. et al. Bacterial exploitation of phosphorylcholine mimicry suppresses inflammation to promote airway infection. J. Clin. Invest. 125, 3878–3890 (2015).
Andre, G. O. et al. Role of Streptococcus pneumoniae proteins in evasion of complement-mediated immunity. Front. Microbiol. 8, 224 (2017).
Hyams, C., Camberlein, E., Cohen, J. M., Bax, K. & Brown, J. S. The Streptococcus pneumoniae capsule inhibits complement activity and neutrophil phagocytosis by multiple mechanisms. Infect. Immun. 78, 704–715 (2010).
Hyams, C. et al. Streptococcus pneumoniae capsular serotype invasiveness correlates with the degree of factor H binding and opsonization with C3b/iC3b. Infect. Immun. 81, 354–363 (2013).
Hammerschmidt, S., Talay, S. R., Brandtzaeg, P. & Chhatwal, G. S. SpsA, a novel pneumococcal surface protein with specific binding to secretory immunoglobulin A and secretory component. Mol. Microbiol. 25, 1113–1124 (1997).
Dieudonne-Vatran, A. et al. Clinical isolates of Streptococcus pneumoniae bind the complement inhibitor C4b-binding protein in a PspC allele-dependent fashion. J. Immunol. 182, 7865–7877 (2009).
Kohler, S. et al. Binding of vitronectin and Factor H to Hic contributes to immune evasion of Streptococcus pneumoniae serotype 3. Thromb. Haemostasis 113, 125–142 (2015).
Tu, A. H., Fulgham, R. L., McCrory, M. A., Briles, D. E. & Szalai, A. J. Pneumococcal surface protein A inhibits complement activation by Streptococcus pneumoniae. Infect. Immun. 67, 4720–4724 (1999).
Paton, J. C., Rowan-Kelly, B. & Ferrante, A. Activation of human complement by the pneumococcal toxin pneumolysin. Infect. Immun. 43, 1085–1087 (1984).
Yuste, J., Botto, M., Paton, J. C., Holden, D. W. & Brown, J. S. Additive inhibition of complement deposition by pneumolysin and PspA facilitates Streptococcus pneumoniae septicemia. J. Immunol. 175, 1813–1819 (2005).
Dalia, A., Standish, A. & Weiser, J. Three surface exoglycosidases from Streptococcus pneumoniae, NanA, BgaA, and StrH, promote resistance to opsonophagocytic killing by human neutrophils. Infect. Immun. 78, 2108–2116 (2010).
Dalia, A. & Weiser, J. Minimization of bacterial size allows for complement evasion and is overcome by the agglutinating effect of antibody. Cell Host Microbe 10, 486–496 (2011).
O’Brien, K. L. et al. Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial. J. Infect. Dis. 196, 1211–1220 (2007).
Geno, K. A. et al. Pneumococcal capsules and their types: past, present, and future. Clin. Microbiol. Rev. 28, 871–899 (2015).
Klugman, K. The significance of serotype replacement for pneumococcal disease and antibiotic resistance. Adv. Exp. Med. Biol. 634, 121–128 (2009).
von Gottberg, A. et al. Effects of vaccination on invasive pneumococcal disease in South Africa. N. Engl. J. Med. 371, 1889–1899 (2014).