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| Jeffrey WeiserSummaryAffiliation: University of Pennsylvania Country: USA Publications
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Publications
The battle with the host over microbial sizeJeffrey N Weiser
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States Electronic address
Curr Opin Microbiol 16:59-62. 2013..Some successful pathogens in turn are able to prevent immune mediated clearance by expressing virulence factors that block agglutination. Thus, microbial size is one of the battlegrounds between microbial survival and host defense...
Within-host competition drives selection for the capsule virulence determinant of Streptococcus pneumoniaeElena S Lysenko
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Curr Biol 20:1222-6. 2010..pneumoniae type during competition. Our findings demonstrate that competition between microbes during their commensal state may underlie selection for characteristics that allow invasive disease...- Antibody-enhanced pneumococcal adherence requires IgA1 proteaseJeffrey N Weiser
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 100:4215-20. 2003..These enzymes may enable pathogens to subvert the antigen specificity of the humoral immune response to facilitate adhesive interactions and persistence on the mucosal surface... - Early bacterial colonization induces toll-like receptor-dependent transforming growth factor beta signaling in the epitheliumChristoph Beisswenger
402A Johnson Pavilion, Department of Microbiology and Pediatrics, University of Pennsylvania, Philadelphia, PA 19104 6076, USA
Infect Immun 77:2212-20. 2009..These in vivo data provided a link between inflammation control and maintenance of the mucosal barrier function during infection and emphasized the importance of TLR-dependent inflammatory responses of the respiratory epithelium... - The pneumococcus: why a commensal misbehavesJeffrey N Weiser
Department of Microbiology and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA
J Mol Med (Berl) 88:97-102. 2010..This review summarizes current understanding of how these characteristics may contribute to the commensal lifestyle of the pneumococcus... 
Adaptation of Haemophilus influenzae to acquired and innate humoral immunity based on phase variation of lipopolysaccharideJ N Weiser
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia 19104 6076, USA
Mol Microbiol 30:767-75. 1998..Genetic analysis of NTHi within the human respiratory tract demonstrated that Galalpha1-4Gal may not be expressed during carriage but may be advantageous for the organism in inflammatory states such as pneumonia...- Changes in availability of oxygen accentuate differences in capsular polysaccharide expression by phenotypic variants and clinical isolates of Streptococcus pneumoniaeJ N Weiser
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Infect Immun 69:5430-9. 2001..Differences in the availability of oxygen, therefore, may be a key factor in allowing for the selection of distinct phenotypes in these two host environments... - Effect of intrastrain variation in the amount of capsular polysaccharide on genetic transformation of Streptococcus pneumoniae: implications for virulence studies of encapsulated strainsJ N Weiser
Departments of Pediatrics and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Infect Immun 67:3690-2. 1999..Genetic transformation, therefore, tends to select for a less-encapsulated subpopulation... - Decoration of lipopolysaccharide with phosphorylcholine: a phase-variable characteristic of Haemophilus influenzaeJ N Weiser
Department of Pediatrics, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, 19104 4318, USA
Infect Immun 65:943-50. 1997..In the case of H. influenzae, its primary contribution to pathogenesis does not appear to be antigenic variation to evade host humoral clearance mechanisms... - Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive proteinJ N Weiser
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Exp Med 187:631-40. 1998.... - The phosphorylcholine epitope undergoes phase variation on a 43-kilodalton protein in Pseudomonas aeruginosa and on pili of Neisseria meningitidis and Neisseria gonorrhoeaeJ N Weiser
Departments of Pediatrics and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Infect Immun 66:4263-7. 1998..Expression of the ChoP epitope on piliated neisseriae displayed phase variation, both linked to pilus expression and independently of fully piliated bacteria... - The position of phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae affects binding and sensitivity to C-reactive protein-mediated killingE Lysenko
301B Johnson Pavilion, Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104 6076, USA
Mol Microbiol 35:234-45. 2000..This suggests that, in addition to the mechanism involving phase variation, the structural rearrangements within the oligosaccharide contribute to evasion of innate and acquired immunity... - Identification and characterization of a cell envelope protein of Haemophilus influenzae contributing to phase variation in colony opacity and nasopharyngeal colonizationJ N Weiser
Department of Pediatrics, Children s Hospital of Philadelphia, Pennsylvania, USA
Mol Microbiol 17:555-64. 1995..The type b mutant, however, was as virulent as its parent strain when inoculated intraperitoneally. This suggests that the contribution of OapA to pathogenesis is limited to events associated with colonization of the mucosal surface... - Microarray-based identification of htrA, a Streptococcus pneumoniae gene that is regulated by the CiaRH two-component system and contributes to nasopharyngeal colonizationM E Sebert
Department of Pediatrics, Children's Hospital of Philadelphia, Pennsylvania 19104, USA
Infect Immun 70:4059-67. 2002.... - The transfer of choline from the host to the bacterial cell surface requires glpQ in Haemophilus influenzaeX Fan
Department of Microbiology, 301B Johnson Pavilion, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076, USA
Mol Microbiol 41:1029-36. 2001..In the absence of free choline, this gene was required for adherent H. influenzae to obtain choline directly from epithelial cells in culture. GlpQ therefore allows choline to be transferred from the host to the bacterial cell surface... - The genetic basis of colony opacity in Streptococcus pneumoniae: evidence for the effect of box elements on the frequency of phenotypic variationS K Saluja
University of Pennsylvania School of Medicine, Philadelphia 19104, USA
Mol Microbiol 16:215-27. 1995..Growth characteristics of strains generated in this study provide additional evidence for an association of differences in cell wall autolysis and variation in colony opacity... - Expression of C-reactive protein in the human respiratory tractJ M Gould
Division of Pediatric Infectious Diseases, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
Infect Immun 69:1747-54. 2001.... - Pneumococcal HtrA protease mediates inhibition of competence by the CiaRH two-component signaling systemM E Sebert
Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Bacteriol 187:3969-79. 2005..These findings suggest a novel regulatory role for pneumococcal HtrA in modulating the activity of a two-component signaling system that controls the development of genetic competence... - Binding of the non-typeable Haemophilus influenzae lipooligosaccharide to the PAF receptor initiates host cell signallingW E Swords
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Cell Microbiol 3:525-36. 2001..Moreover, the data suggest that NTHi strains initiate cell signalling and invade by different mechanisms, and that invasion mediated by PAF receptor activation is more efficient than macropinocytosis... - Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2Michael A Bachman
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Infect Immun 79:3309-16. 2011..However, Lcn2 retained partial protection against disseminated disease. In summary, Ybt is a virulence factor that is prevalent among KPC-producing K. pneumoniae isolates and promotes respiratory tract infections through evasion of Lcn2... - Modifications to the peptidoglycan backbone help bacteria to establish infectionKimberly M Davis
Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
Infect Immun 79:562-70. 2011..This review will focus specifically on peptidoglycan modifications, their role in lysozyme resistance, and downstream effects on the host immune response to infection... - Identification, cloning, and sequencing of the immunoglobulin A1 protease gene of Streptococcus pneumoniaeJ H Wani
Department of Pediatrics, Children s Hospital of Philadelphia, Pennsylvania, USA
Infect Immun 64:3967-74. 1996..Interruption of the chromosomal gene resulted in loss of expression of an approximately 200-kDa protein and complete elimination of detectable IgA1 protease activity... - Epithelial cells are sensitive detectors of bacterial pore-forming toxinsAdam J Ratner
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 281:12994-8. 2006..Osmosensing may thus represent a novel innate immune response to a common bacterial virulence strategy... - The atypical amino-terminal LPNTG-containing domain of the pneumococcal human IgA1-specific protease is required for proper enzyme localization and functionMatthew H Bender
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Mol Microbiol 61:526-43. 2006..This amino-terminal motif is shared among the other zinc metalloproteinases in streptococci and suggests a novel conserved mechanism for the surface localization of protease activity... - Impact of the molecular form of immunoglobulin A on functional activity in defense against Streptococcus pneumoniaeClaudine E Fasching
Division of Infectious Diseases and International Medicine, Veterans Affairs Medical Center, University of Minnesota, Minneapolis, MN, USA
Infect Immun 75:1801-10. 2007..In summary, the polymeric forms of IgA (both pIgA and SIgA) provide a substantial advantage in binding, agglutination, and OPC of the organism... - Live attenuated Streptococcus pneumoniae strains induce serotype-independent mucosal and systemic protection in miceAoife M Roche
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104 6076, USA
Infect Immun 75:2469-75. 2007..Thus, colonization by live attenuated S. pneumoniae is a potentially safe and less complex vaccine strategy that may offer broad protection... - Nod1 mediates cytoplasmic sensing of combinations of extracellular bacteriaAdam J Ratner
Departments of Microbiology and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Cell Microbiol 9:1343-51. 2007..We conclude that combinations of extracellular organisms can activate innate immune pathways previously considered to be reserved for the detection of intracellular microorganisms... - Role of p38 MAP kinase and transforming growth factor-beta signaling in transepithelial migration of invasive bacterial pathogensChristoph Beisswenger
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 282:28700-8. 2007..pneumoniae or H. influenzae. Our data shows that diverse bacteria utilize common mechanisms, including MAPK and TGF-beta signaling pathways to disrupt epithelial barriers and promote invasion... - Neutrophil-toxin interactions promote antigen delivery and mucosal clearance of Streptococcus pneumoniaeKathryn A Matthias
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
J Immunol 180:6246-54. 2008..This study demonstrates how microbial-host interactions affect Ag delivery and the effectiveness of mucosal immunity... - Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniaeSamantha J King
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Mol Microbiol 59:961-74. 2006..pneumoniae to deglycosylate human targets and suggest that in addition to NanA, BgaA and StrH also contribute to pneumococcal colonization and/or pathogenesis... - Host and bacterial factors contributing to the clearance of colonization by Streptococcus pneumoniae in a murine modelAnnemarie M C van Rossum
University of Pennsylvania, 402A Johnson Pavilion, Philadelphia, PA 19104 6076, USA
Infect Immun 73:7718-26. 2005..We conclude that both innate and CD4+ T-cell-mediated immunity and proinflammatory bacterial factors, rather than a humoral adaptive immune response, are important for clearance of S. pneumoniae from the murine nasopharynx... - Bacterial colonization of nasal mucosa induces expression of siderocalin, an iron-sequestering component of innate immunityAaron L Nelson
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
Cell Microbiol 7:1404-17. 2005..influenzae are known to produce or utilize siderophores, successful colonizers of the nasal passages may have evolved siderophore-independent mechanisms to acquire essential iron and to evade the inhibitory effects of Scn... - Toll-like receptor 4 mediates innate immune responses to Haemophilus influenzae infection in mouse lungXiaorong Wang
Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 168:810-5. 2002..influenzae in the lung. This suggests that the airway epithelia might contribute to sensing of H. influenzae infection and signaling the innate immune response... - The immune response to pneumococcal proteins during experimental human carriageTera L McCool
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA
J Exp Med 195:359-65. 2002..Our findings provide evidence for the role of antibody to this protein fragment in preventing pneumococcal carriage by humans... - The inhibitory effect of C-reactive protein on bacterial phosphorylcholine platelet-activating factor receptor-mediated adherence is blocked by surfactantJane M Gould
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia 19104 6076, USA
J Infect Dis 186:361-71. 2002..The binding of CRP to ChoP and the effect of CRP on adherence were inhibited by human surfactant (primarily ChoP). The antiadhesive effect of CRP may be diminished in the terminal airway, where surfactant is abundant... - Neuraminidase expressed by Streptococcus pneumoniae desialylates the lipopolysaccharide of Neisseria meningitidis and Haemophilus influenzae: a paradigm for interbacterial competition among pathogens of the human respiratory tractElizabeth A Shakhnovich
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
Infect Immun 70:7161-4. 2002..We show that a neuraminidase expressed by Streptococcus pneumoniae (NanA) is able to desialylate the cell surfaces of both these species, which reside in and possibly compete for the same host niche... - Serum immunoglobulin G response to candidate vaccine antigens during experimental human pneumococcal colonizationTera L McCool
Department of Microbiology and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Infect Immun 71:5724-32. 2003..These findings support the need for further investigation of the human antibody response to PspA and CbpA and the potential use of one or both of these proteins as novel vaccine antigens for the prevention of pneumococcal colonization... - Multiple mechanisms for choline transport and utilization in Haemophilus influenzaeXin Fan
University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Mol Microbiol 50:537-48. 2003..We conclude that H. influenzae may have multiple mechanisms for choline uptake and distinct pathways for choline utilization in LPS-ChoP biosynthesis and osmoregulation... - Synergistic proinflammatory responses induced by polymicrobial colonization of epithelial surfacesAdam J Ratner
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 102:3429-34. 2005..These synergistic responses, demonstrated both in vitro and in vivo, may contribute to inflammation of heavily colonized mucosal barriers... - Cross-reactivity of human immunoglobulin G2 recognizing phosphorylcholine and evidence for protection against major bacterial pathogens of the human respiratory tractHannah B Goldenberg
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076, USA
J Infect Dis 190:1254-63. 2004..pneumoniae type 6A. The effectiveness of human antibody to this conserved bacterial structure suggests that, if it can be manipulated to broaden its activity, it could function as a single vaccine antigen that targets multiple pathogens... - Limited role of antibody in clearance of Streptococcus pneumoniae in a murine model of colonizationTera L McCool
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6076, USA
Infect Immun 72:5807-13. 2004..These results demonstrate that antibody is not required for clearance of pneumococcal colonization in mice... - Phase variable desialylation of host proteins that bind to Streptococcus pneumoniae in vivo and protect the airwaySamantha J King
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Mol Microbiol 54:159-71. 2004..pneumoniae. Because deglycosylation affects the function of many host proteins, NanA may contribute to a protease-independent mechanism to modify bound targets and facilitate enhanced survival of the bacterium... - Effect of pneumococcal polysaccharide vaccine on nonbacteremic pneumococcal pneumoniaJeffrey N Weiser
Clin Infect Dis 44:1139-40; author reply 1140-1. 2007 - beta-Defensin 1 contributes to pulmonary innate immunity in miceChristian Moser
Institute for Human Gene Therapy, Departments of Medicine and Molecular and Cellular Engineering, University of Pennsylvania, Philadelphia 19104, USA
Infect Immun 70:3068-72. 2002..We find that loss of mBD-1 results in delayed clearance of Haemophilus influenzae from lung. These data demonstrate directly that antimicrobial peptides of vertebrates provide an initial block to bacteria at epithelial surfaces... - The blp bacteriocins of Streptococcus pneumoniae mediate intraspecies competition both in vitro and in vivoSuzanne Dawid
Department of Microbiology, University of Pennsylvania, 402A Johnson Pavilion, Philadelphia, PA 19104 6076, USA
Infect Immun 75:443-51. 2007.... - Short-sequence tandem and nontandem DNA repeats and endogenous hydrogen peroxide production contribute to genetic instability of Streptococcus pneumoniaeChristopher D Pericone
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6076, USA
J Bacteriol 184:4392-9. 2002..Some of these mutations appear to have been selected for in vivo during pneumococcal infection, perhaps as a consequence of immune pressure or oxidative stress... - Capsule enhances pneumococcal colonization by limiting mucus-mediated clearanceAaron L Nelson
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6076, USA
Infect Immun 75:83-90. 2007..In conclusion, our findings demonstrate that capsule confers an advantage to mucosal pathogens distinct from its role in inhibition of opsonophagocytosis--escape from entrapment in lumenal mucus... - The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and diseaseAras Kadioglu
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom
Nat Rev Microbiol 6:288-301. 2008..In this Review, we describe how S. pneumoniae uses its armamentarium of virulence factors to colonize the upper and lower respiratory tracts of the host and cause disease... - Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killingElena S Lysenko
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
PLoS Pathog 3:e118. 2007..These observations offer insight into mechanisms of microbial competition and demonstrate the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo... - Identifying mutator phenotypes among fluoroquinolone-resistant strains of Streptococcus pneumoniae using fluctuation analysisCarolyn V Gould
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Antimicrob Agents Chemother 51:3225-9. 2007.... - Factors contributing to hydrogen peroxide resistance in Streptococcus pneumoniae include pyruvate oxidase (SpxB) and avoidance of the toxic effects of the fenton reactionChristopher D Pericone
Departments of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Bacteriol 185:6815-25. 2003..pneumoniae has a novel mechanism to avoid the toxic effects of the Fenton reaction... - Interleukin-8 secretion in response to aferric enterobactin is potentiated by siderocalinAaron L Nelson
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104 6076, USA
Infect Immun 75:3160-8. 2007..This may be a novel mechanism for the mucosa to respond to metabolic signals of expanding microbial communities...
Research Grants
- Training in bacteriologyJeffrey Weiser; Fiscal Year: 2007....
- BACTERIAL PHOSPHORYLCHOLINE AND PATHOGENESISJeffrey Weiser; Fiscal Year: 2009..Aim 3 will determine the effects of the immune response to ChoP on colonization, where our findings demonstrate that expression of ChoP is most important to pathogenesis. ..
- Mechanisms of pneumococcal persistence during carriageJeffrey Weiser; Fiscal Year: 2009..In specific aim #3, we will examine the effect of pneumococcal colonization on plasma cell activity and define pneumococcal factors that affect the production of secretory immunoglobulin. ..
- Bacterial and host factors in pneumococcal competitionJeffrey Weiser; Fiscal Year: 2009....
- Bacterial and host factors in pneumococcal competitionJeffrey N Weiser; Fiscal Year: 2010....
- Mechanisms of pneumococcal persistence during carriage.Jeffrey N Weiser; Fiscal Year: 2010..The proposed studies provide a mechanistic understanding of i) its ability to inhibit uptake and killing by neutrophils, ii) its recognition by macrophages, and iii) the role of its capsule type in these interactions with phagocytes. ..
- BACTERIAL PHOSPHORYLCHOLINE AND PATHOGENESISJeffrey Weiser; Fiscal Year: 2003....
- Competition Among Bacterial Resiratory PathogensJeffrey Weiser; Fiscal Year: 2004..Future strategies to decrease disease burden by reducing carriage could result from a greater understanding of interactions between species. ..
- ROLE OF OPACITY VARIATION IN PNEUMOCOCCAL PATHOGENESISJeffrey Weiser; Fiscal Year: 2004..The hope here is to isolate transcription factors that may function as global regulators affecting pyruvate oxidase. ..
- Bacterial and host factors in pneumococcal competitionJeffrey N Weiser; Fiscal Year: 2011....