Search

Your search keyword '"Alice S. Prince"' showing total 17 results
Start Over Author "Alice S. Prince"
17 results on '"Alice S. Prince"'

1. Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst

Author

Kira L. Tomlinson, Sebastián A. Riquelme, Swikrity Upadhyay Baskota, Marija Drikic, Ian R. Monk, Timothy P. Stinear, Ian A. Lewis, and Alice S. Prince

Subjects
CP: Immunology, CP: Microbiology, Biology (General), QH301-705.5
Abstract

Summary: Neutrophils are critical in the host defense against Staphylococcus aureus, a major human pathogen. However, even in the setting of a robust neutrophil response, S. aureus can evade immune clearance. Here, we demonstrate that S. aureus impairs neutrophil function by triggering the production of the anti-inflammatory metabolite itaconate. The enzyme that synthesizes itaconate, Irg1, is selectively expressed in neutrophils during S. aureus pneumonia. Itaconate inhibits neutrophil glycolysis and oxidative burst, which impairs survival and bacterial killing. In a murine pneumonia model, neutrophil Irg1 expression protects the lung from excessive inflammation but compromises bacterial clearance. S. aureus is thus able to evade the innate immune response by targeting neutrophil metabolism and inducing the production of the anti-inflammatory metabolite itaconate.

Published
2023
Full Text
View/download PDF

2. Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation

Author

Kira L. Tomlinson, Tania Wong Fok Lung, Felix Dach, Medini K. Annavajhala, Stanislaw J. Gabryszewski, Ryan A. Groves, Marija Drikic, Nancy J. Francoeur, Shwetha H. Sridhar, Melissa L. Smith, Sara Khanal, Clemente J. Britto, Robert Sebra, Ian Lewis, Anne-Catrin Uhlemann, Barbara C. Kahl, Alice S. Prince, and Sebastián A. Riquelme

Subjects
Science
Abstract

The authors show that the pathogen Staphylococcus aureus induces a distinct airway immunometabolic response, dominated by release of itaconate. This metabolite, in turn, potentiates extracellular polysaccharide synthesis and biofilm formation in S. aureus, which may facilitate chronic infection.

Published
2021
Full Text
View/download PDF

3. Immunometabolites Drive Bacterial Adaptation to the Airway

Author

Kira L. Tomlinson, Alice S. Prince, and Tania Wong Fok Lung

Subjects
immunometabolism, host-pathogen interaction, bacterial persistence, metabolic adaptation, itaconate, succinate, Immunologic diseases. Allergy, RC581-607
Abstract

Pseudomonas aeruginosa and Staphylococcus aureus are both opportunistic pathogens that are frequently associated with chronic lung infections. While bacterial virulence determinants are critical in initiating infection, the metabolic flexibility of these bacteria promotes their persistence in the airway. Upon infection, these pathogens induce host immunometabolic reprogramming, resulting in an airway milieu replete with immune-signaling metabolites. These metabolites are often toxic to the bacteria and create a steep selection pressure for the emergence of bacterial isolates adapted for long-term survival in the inflamed lung. In this review, we discuss the main differences in the host immunometabolic response to P. aeruginosa and S. aureus, as well as how these pathogens alter their own metabolism to adapt to airway metabolites and cause persistent lung infections.

Published
2021
Full Text
View/download PDF

5. Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to Staphylococcus aureus Superinfection

Author

Paul J. Planet, Dane Parker, Taylor S. Cohen, Hannah Smith, Justinne D. Leon, Chanelle Ryan, Tobin J. Hammer, Noah Fierer, Emily I. Chen, and Alice S. Prince

Subjects
Microbiology, QR1-502
Abstract

ABSTRACT Much of the morbidity and mortality associated with influenza virus respiratory infection is due to bacterial coinfection with pathogens that colonize the upper respiratory tract such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae. A major component of the immune response to influenza virus is the production of type I and III interferons. Here we show that the immune response to infection with influenza virus causes an increase and restructuring of the upper respiratory microbiota in wild-type (WT) mice but not in Il28r−/− mutant mice lacking the receptor for type III interferon. Mice lacking the IL-28 receptor fail to induce STAT1 phosphorylation and expression of its regulator, SOCS1. Il28r−/− mutant mice have increased expression of interleukin-22 (IL-22), as well as Ngal and RegIIIγ, in the nasal cavity, the source of organisms that would be aspirated to cause pneumonia. Proteomic analysis reveals changes in several cytoskeletal proteins that contribute to barrier function in the nasal epithelium that may contribute to the effects of IL-28 signaling on the microbiota. The importance of the effects of IL-28 signaling in the pathogenesis of MRSA pneumonia after influenza virus infection was confirmed by showing that WT mice nasally colonized before or after influenza virus infection had significantly higher levels of infection in the upper airways, as well as significantly greater susceptibility to MRSA pneumonia than Il28r−/− mutant mice did. Our results suggest that activation of the type III interferon in response to influenza virus infection has a major effect in expanding the upper airway microbiome and increasing susceptibility to lower respiratory tract infection. IMPORTANCE S. aureus and influenza virus are important respiratory pathogens, and coinfection with these organisms is associated with significant morbidity and mortality. The ability of influenza virus to increase susceptibility to S. aureus infection is less well understood. We show here that influenza virus leads to a change in the upper airway microbiome in a type III interferon-dependent manner. Mice lacking the type III interferon receptor have altered STAT1 and IL-22 signaling. In coinfection studies, mice without the type III interferon receptor had significantly less nasal S. aureus colonization and subsequent pneumonia than infected WT mice did. This work demonstrates that type III interferons induced by influenza virus contribute to nasal colonization and pneumonia due to S. aureus superinfection.

Published
2016
Full Text
View/download PDF

6. Cystic fibrosis: a mucosal immunodeficiency syndrome

Author

Taylor S. Cohen and Alice S. Prince

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Cystic Fibrosis, Respiratory System, Mutant, Cystic Fibrosis Transmembrane Conductance Regulator, Inflammation, Cystic fibrosis, Article, General Biochemistry, Genetics and Molecular Biology, Immunodeficiency Syndrome, medicine, Animals, Humans, Mucous Membrane, Lung, Innate immune system, biology, business.industry, Immunologic Deficiency Syndromes, Mucous membrane, General Medicine, respiratory system, medicine.disease, Cystic fibrosis transmembrane conductance regulator, respiratory tract diseases, Phenotype, medicine.anatomical_structure, Mutation, Immunology, biology.protein, medicine.symptom, business
Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a channel that regulates the transport of ions and the movement of water across the epithelial barrier. Mutations in CFTR, which form the basis for the clinical manifestations of cystic fibrosis, affect the epithelial innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation that fails to eradicate pulmonary pathogens. Compounding the effects of excessive neutrophil recruitment, the mutant CFTR channel does not transport antioxidants to counteract neutrophil-associated oxidative stress. Whereas mutant CFTR expression in leukocytes outside of the lung does not markedly impair their function, the expected regulation of inflammation in the airways is clearly deficient in cystic fibrosis. The resulting bacterial infections, which are caused by organisms that have substantial genetic and metabolic flexibility, can resist multiple classes of antibiotics and evade phagocytic clearance. The development of animal models that approximate the human pulmonary phenotypes—airway inflammation and spontaneous infection—may provide the much-needed tools to establish how CFTR regulates mucosal immunity and to test directly the effect of pharmacologic potentiation and correction of mutant CFTR function on bacterial clearance.

Published
2012
Full Text
View/download PDF

7. Redundant phenazine operons in Pseudomonas aeruginosa exhibit environment-dependent expression and differential roles in pathogenicity

Author

Adriana Hernandez, Taylor S. Cohen, Alexa Price-Whelan, Hassan Sakhtah, Alice S. Prince, Lars E. P. Dietrich, David A. Recinos, and Matthew D. Sekedat

Subjects
Operon, Mutant, Phenazine, Colony Count, Microbial, Virulence, Biology, Environment, Quinolones, medicine.disease_cause, Models, Biological, Bacterial genetics, Microbiology, chemistry.chemical_compound, Mice, medicine, Animals, Pseudomonas Infections, Gene, Lung, Regulation of gene expression, Multidisciplinary, Pseudomonas aeruginosa, Gene Expression Regulation, Bacterial, Biological Sciences, Plankton, Mice, Inbred C57BL, Disease Models, Animal, chemistry, Genes, Bacterial, Biofilms, Phenazines
Abstract

Evolutionary biologists have postulated that several fitness advantages may be conferred by the maintenance of duplicate genes, including environmental adaptation resulting from differential regulation. We examined the expression and physiological contributions of two redundant operons in the adaptable bacterium Pseudomonas aeruginosa PA14. These operons, phzA1-G1 ( phz1 ) and phzA2-G2 ( phz2 ), encode nearly identical sets of proteins that catalyze the synthesis of phenazine-1-carboxylic acid, the precursor for several phenazine derivatives. Phenazines perform diverse roles in P. aeruginosa physiology and act as virulence factors during opportunistic infections of plant and animal hosts. Although reports have indicated that phz1 is regulated by the Pseudomonas quinolone signal, factors controlling phz2 expression have not been identified, and the relative contributions of these redundant operons to phenazine biosynthesis have not been evaluated. We found that in liquid cultures, phz1 was expressed at higher levels than phz2 , although phz2 showed a greater contribution to phenazine production. In colony biofilms, phz2 was expressed at high levels, whereas phz1 expression was not detectable, and phz2 was responsible for virtually all phenazine production. Analysis of mutants defective in quinolone signal synthesis revealed a critical role for 4-hydroxy-2-heptylquinoline in phz2 induction. Finally, deletion of phz2 , but not of phz1 , decreased lung colonization in a murine model of infection. These results suggest that differential regulation of the redundant phz operons allows P. aeruginosa to adapt to diverse environments.

Published
2012

8. Contributors

Author

Elisabeth E. Adderson, Aarti Agarwal, Grace M. Aldrovandi, Upton D. Allen, Manuel R. Amieva, Krow Ampofo, Alicia D. Anderson, Margot Anderson, Paul M. Arguin, John C. Arnold, Ann M. Arvin, Shai Ashkenazi, Carol J. Baker, William J. Barson, Daniel G. Bausch, Kirsten Bechtel, Daniel K. Benjamin, Frank E. Berkowitz, Margaret J. Blythe, Joseph A. Bocchini, Michael Boeckh, Anna Bowen, William R. Bowie, Thomas G. Boyce, John S. Bradley, Michael T. Brady, Denise F. Bratcher, Paula K. Braverman, Caroline Breese Hall, Joseph S. Bresee, Itzhak Brook, Kristina Bryant, E. Stephen Buescher, Jane L. Burns, Gale R. Burstein, Carrie L. Byington, Kathy K. Byrd, Michael Cappello, Bryan D. Carter, Emily J. Cartwright, Mary T. Caserta, Chiara Cerini, Ellen Gould Chadwick, Beth Cheesebrough, P. Joan Chesney, John C. Christenson, Thomas G. Cleary, Susan E. Coffin, Laura M. Conklin, Laurie S. Conklin, Beverly L. Connelly, Despina Contopoulos-Ioannidis, James H. Conway, Margaret M. Cortese, C. Michael Cotten, Elaine Cox, Maryanne E. Crockett, James E. Crowe, Nigel Curtis, Dennis J. Cunningham, Linda Marie Dairiki Shortliffe, Toni Darville, Gregory A. Dasch, Irini Daskalaki, Robert S. Daum, Fatimah S. Dawood, Gail J. Demmler, Dickson D. Despommier, Karen A. Diefenbach, Christopher C. Dvorak, Kathryn M. Edwards, Morven S. Edwards, Lawrence F. Eichenfield, Dirk M. Elston, Janet A. Englund, Veronique Erard, Marina E. Eremeeva, Anat R. Feingold, Adam Finn, Anthony E. Fiore, Marc Fischer, Sarah J. Fitch, Patricia M. Flynn, LeAnne M. Fox, Michael M. Frank, Douglas R. Fredrick, Sheila Fallon Friedlander, Hayley A. Gans, Carla G. Garcia, Maria C. Garzon, Jeffrey S. Gerber, Michael D. Geschwind, Laura B. Gieraltowski, Francis Gigliotti, Peter H. Gilligan, Carol Glaser, Benjamin D. Gold, Brahm Goldstein, Jane M. Gould, Michael Green, David Greenberg, Patricia M. Griffin, Alexei A. Grom, Kathleen Gutierrez, Judith A. Guzman-Cottrill, Aron J. Hall, Marvin B. Harper, Christopher J. Harrison, David B. Haslam, Sarah J. Hawkes, Edward B. Hayes, Rohan Hazra, Sara Jane Heilig, J. Owen Hendley, Marion C.W. Henry, Joseph A. Hilinski, Scott D. Holmberg, Deborah Holtzman, Peter J. Hotez, Katherine K. Hsu, Dale J. Hu, Loris Y. Hwang, David Y. Hyun, Mary Anne Jackson, Richard F. Jacobs, Jeffrey L. Jones, Saleem Kamili, M. Gary Karlowicz, Ben Z. Katz, Gilbert J. Kersh, Laura M. Kester, Jay S. Keystone, David W. Kimberlin, Martin B. Kleiman, Mark W. Kline, Andrew Y. Koh, Andreas Konstantopoulos, Katalin I. Koranyi, E. Kent Korgenski, Andrew T. Kroger, Paul Krogstad, Christine T. Lauren, Hillary S. Lawrence, Eugene Leibovitz, Stéphanie Levasseur, David B. Lewis, Jay M. Lieberman, Jen-Jane Liu, Robyn A. Livingston, Eloisa Llata, Anagha R. Loharikar, Sarah S. Long, Ben A. Lopman, Bennett Lorber, Donald E. Low, Yalda C. Lucero, Jorge Luján-Zilbermann, Katherine Luzuriaga, Noni E. MacDonald, Adam MacNeil, Yvonne A. Maldonado, Chitra S. Mani, Mario J. Marcon, Gary S. Marshall, Stacey W. Martin, Catalina Matiz, Alison C. Mawle, Tony Mazzulli, George H. McCracken, Matthew B. McDonald, Robert S. McGregor, Kenneth McIntosh, Meredith McMorrow, Candice McNeil, Jennifer H. McQuiston, Debrah Meislich, H. Cody Meissner, Asunción Mejías, Manoj P. Menon, Jussi Mertsola, Marian G. Michaels, Melissa B. Miller, Eric D. Mintz, John F. Modlin, Parvathi Mohan, Susan P. Montgomery, Jose G. Montoya, Zack S. Moore, Maite de la Morena, Pedro L. Moro, Anna-Barbara Moscicki, R. Lawrence Moss, Trudy V. Murphy, Dennis L. Murray, Angela L. Myers, Simon Nadel, James P. Nataro, Michael N. Neely, William L. Nicholson, Victor Nizet, Amy Jo Nopper, Anna Norrby-Teglund, Theresa J. Ochoa, Miguel O’Ryan, Walter A. Orenstein, Christopher D. Paddock, Diane E. Pappas, Robert F. Pass, Thomas F. Patterson, Stephen I. Pelton, Larry K. Pickering, Caroline Diane Sarah Piggott, Philip A. Pizzo, Andrew J. Pollard, Klara M. Posfay-Barbe, Susan M. Poutanen, Dwight A. Powell, Alice S. Prince, Charles G. Prober, Octavio Ramilo, Shawn J. Rangel, Sarah A. Rawstron, Jennifer S. Read, Michael D. Reed, Joanna J. Regan, Megan E. Reller, Melissa A. Reyes, Peter A. Rice, Samuel E. Rice-Townsend, Frank O. Richards, Gail L. Rodgers, Pierre E. Rollin, José R. Romero, G. Ingrid J.G. Rours, Anne H. Rowley, Sharon L. Roy, Lorry G. Rubin, Guillermo M. Ruiz-Palacios, Lisa Saiman, Laura Sass, Jason B. Sauberan, Peter M. Schantz, Eileen Schneider, Gordon E. Schutze, Benjamin Schwartz, Heidi Schwarzwald, Kara N. Shah, Samir S. Shah, Andi L. Shane, Craig A. Shapiro, Eugene D. Shapiro, Umid M. Sharapov, Jana Shaw, George Kelly Siberry, Jane D. Siegel, Robert David Siegel, Nalini Singh, Upinder Singh, P. Brian Smith, John D. Snyder, David E. Soper, Mary Allen Staat, J. Erin Staples, Jeffrey R. Starke, William J. Steinbach, Ina Stephens, Joseph W. St. Geme, Bradley P. Stoner, Jonathan B. Strober, Kanta Subbarao, Deanna A. Sutton, Douglas Swanson, Leonel T. Takada, Jacqueline E. Tate, Robert V. Tauxe, Marc Tebruegge, Eyasu H. Teshale, George R. Thompson, Herbert A. Thompson, Richard B. Thomson, Emily A. Thorell, Rania A. Tohme, Robert W. Tolan, Philip Toltzis, James Treat, Stephanie B. Troy, Russell B. Van Dyke, Jorge J. Velarde, Jennifer Vodzak, Ellen R. Wald, Geoffrey A. Weinberg, A. Clinton White, Marc-Alain Widdowson, Harold C. Wiesenfeld, John V. Williams, Roxanne E. Williams, Rodney E. Willoughby, Craig M. Wilson, Sarah L. Wingerter, Jerry A. Winkelstein, Kimberly A. Workowski, Terry W. Wright, Pablo Yagupsky, Nada Yazigi, Catherine Yen, Edward J. Young, Andrea L. Zaenglein, and Theoklis E. Zaoutis

Published
2012
Full Text
View/download PDF

10. Contributors

Author

Elisabeth E. Adderson, Felice C. Adler-Shohet, Manuel R. Amieva, Gregory L. Armstrong, Wences Arvelo, Ann M. Arvin, David M. Asher, Shai Ashkenazi, Kevin A. Ault, Carol J. Baker, William J. Barson, Beth P. Bell, Michael J. Bell, Daniel K. Benjamin, Stephanie R. Bialek, Margaret J. Blythe, Joseph A. Bocchini, Michael Boeckh, William A. Bower, Kenneth M. Boyer, Christopher R. Braden, John S. Bradley, Michael T. Brady, Denise Bratcher, Paula K. Braverman, Joseph S. Bresee, Itzhak Brook, Kevin E. Brown, John C. Browning, Steven C. Buckingham, E. Stephen Buescher, Jane L. Burns, Michael Cappello, Bryan D. Carter, Ellen Gould Chadwick, Patricia Joan Chesney, James E. Childs, John C. Christenson, Thomas G. Cleary, Susan E. Coffin, Beverly L. Connelly, C. Michael Cotton, Elaine Cox, Robert Andrew Cramer, Maryanne E. Crockett, James E. Crowe, Dennis J. Cunningham, Toni Darville, Gregory A. Dasch, Robert S. Daum, Maite de la Morena, Gail J. Demmler, Dickson D. Despommier, Karen A. Diefenbach, Elidia Dominguez, Stephen M. Downs, Christopher C. Dvorak, Kathryn Edwards, Morven S. Edwards, Janet A. Englund, Véronique Erard, Marina E. Eremeeva, Lyn Finelli, Adam Finn, Anthony E. Fiore, Marc Fischer, Sarah J. Fitch, Patricia M. Flynn, J. Dennis Fortenberry, LeAnne M. Fox, David O. Freedman, Hayley A. Gans, Michael A. Gerber, Francis Gigliotti, Peter Gilligan, Benjamin D. Gold, David L. Goldman, Brahm Goldstein, Susan T. Goldstein, Jane M. Gould, Michael Green, Sharon K. Greene, Mark J. Greenwald, Alexei A. Grom, Leigh B. Grossman, Marta A. Guerra, Kathleen Gutierrez, Judith A. Guzman-Cottrill, Caroline Breese Hall, Marvin B. Harper, David B. Haslam, Edward B. Hayes, J. Owen Hendley, Kelly J. Henrickson, Marion C.W. Henry, Joseph A. Hilinski, Peter J. Hotez, David L. Ingram, Mary Anne Jackson, Richard F. Jacobs, M. Gary Karlowicz, Ben Z. Katz, Jay S. Keystone, David W. Kimberlin, Martin B. Kleiman, Jerome O. Klein, Mark W. Kline, Andrew Y. Koh, Katalin I. Koranyi, E. Kent Korgenski, Robert J. Leggiadro, Moise L. Levy, David B. Lewis, Jay M. Lieberman, Abhijit Limaye, Jacob A. Lohr, Bennett Lorber, Sarah S. Long, Donald E. Low, Gina Lowell, Elizabeth Lowenthal, Jorge Lujan-Zilbermann, Katherine Luzuriaga, Noni E. MacDonald, Yvonne A. Maldonado, Chitra S. Mani, John F. Marcinak, Mario J. Marcon, Gary S. Marshall, Stacey W. Martin, Robert F. Massung, Eric E. Mast, Tony Mazzulli, George H. McCracken, Robert S. McGregor, Kenneth McIntosh, Catherine A. McLean, Rima McLeod, Julia A. McMillan, Jennifer H. McQuiston, H. Cody Meissner, Manoj P. Menon, Marian G. Michaels, Melissa B. Miller, Juan Carlos Millon, John F. Modlin, Matthew R. Moore, Zack S. Moore, Mary M. Moran, Pedro L. Moro, R. Lawrence Moss, Dennis L. Murray, Simon Nadel, James P. Nataro, Michael N. Neely, Victor Nizet, Anna Norrby-Teglund, Ann-Christine Nyquist, Theresa J. Ochoa, Sara M. O'Hara, Walter A. Orenstein, Eduardo Ortega-Barria, Gary D. Overturf, Christopher D. Paddock, John A. Painter, Diane E. Pappas, Monica E. Parise, Robert F. Pass, Thomas F. Patterson, Andrew T. Pavia, Stephen I. Pelton, Georges Peter, Timothy R. Peters, William A. Petri, Larry K. Pickering, Philip A. Pizzo, Andrew J. Pollard, Susan M. Poutanen, Dwight A. Powell, Alice S. Prince, Charles G. Prober, Shawn J. Rangel, Sarah Anne Rawstron, Michael D. Reed, Megan E. Reller, Frank O. Richards, Gail L. Rodgers, Luz I. Romero, Harley A. Rotbart, Anne H. Rowley, Lorry G. Rubin, Guillermo M. Ruiz-Palacios, Xavier Sáez-Llorens, Lisa Saiman, Jason B. Sauberan, Mark H. Sawyer, Peter M. Schantz, Theresa A. Schlager, Gordon E. Schutze, Benjamin Schwartz, Richard H. Schwartz, Heidi Schwarzwald, Samir S. Shah, Andi L. Shane, Eugene D. Shapiro, Avinash K. Shetty, Jane D. Siegel, Robert D. Siegel, Walter E.B. Sipe, Jacek Skarbinski, P. Brian Smith, John D. Snyder, Shahram Solaymani-Mohammadi, Mary Allen Staat, Jeffrey R. Starke, William J. Steinbach, Ina Stephens, Joseph W. St. Geme, Kanta Subbarao, John L. Sullivan, Deanna A. Sutton, Madeline Y. Sutton, David L. Swerdlow, Robert V. Tauxe, Herbert A. Thompson, Richard B. Thomson, Emily A. Thorell, James K. Todd, Philip Toltzis, Theodore F. Tsai, Ellen R. Wald, Richard J. Wallace, Geoffrey A. Weinberg, Avery H. Weiss, A. Clinton White, Marc-Alain Widdowson, Ian T. Williams, John V. Williams, Rodney E. Willoughby, Craig M. Wilson, Jerry A. Winkelstein, Kimberly Workowski, Terry W. Wright, Nada Yazigi, Ram Yogev, Edward J. Young, and Theoklis E. Zaoutis

Published
2008
Full Text
View/download PDF

12. The host response to anthrax lethal toxin: unexpected observations

Author

Alice S. Prince

Subjects
Male, Vascular Endothelial Growth Factor A, Fas Ligand Protein, Virulence Factors, Bacterial Toxins, Endothelial Growth Factors, Thymus Gland, Article, Anthrax, Mice, Bone Marrow, Animals, Hypoxia, Antigens, Bacterial, Lymphokines, Mice, Inbred BALB C, Membrane Glycoproteins, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factors, Macrophages, fungi, General Medicine, bacterial infections and mycoses, Mice, Inbred C57BL, Liver, Commentary, Cytokines, Intercellular Signaling Peptides and Proteins, Spleen, Plasmids
Abstract

Bacillus anthracis lethal toxin (LT) is the major virulence factor of anthrax and reproduces most of the laboratory manifestations of the disease in animals. We studied LT toxicity in BALB/cJ and C57BL/6J mice. BALB/cJ mice became terminally ill earlier and with higher frequency than C57BL/6J mice. Timed histopathological analysis identified bone marrow, spleen, and liver as major affected organs in both mouse strains. LT induced extensive hypoxia. Crisis was due to extensive liver necrosis accompanied by pleural edema. There was no evidence of disseminated intravascular coagulation or renal dysfunction. Instead, analyses revealed hepatic dysfunction, hypoalbuminemia, and vascular/oxygenation insufficiency. Of 50 cytokines analyzed, BALB/cJ mice showed rapid but transitory increases in specific factors including KC, MCP-1/JE, IL-6, MIP-2, G-CSF, GM-CSF, eotaxin, FasL, and IL-1beta. No changes in TNF-alpha occurred. The C57BL/6J mice did not mount a similar cytokine response. These factors were not induced in vitro by LT treatment of toxin-sensitive macrophages. The evidence presented shows that LT kills mice through a TNF-alpha-independent, FasL-independent, noninflammatory mechanism that involves hypoxic tissue injury but does not require macrophage sensitivity to toxin.

Published
2003

13. Hospital Pharmacists and Infectious Diseases Specialists

Author

Linda Ann Sherman, Françoise Meunier, Raleigh A. Bowden, Fred C. Tenover, Alice S. Prince, Michael Barza, Barbara H. Wade, W. Patrick Joseph, Claudio Viscoli, Michael Stek, William A. Craig, Anthony W. Chow, Joseph R. Dalovisio, Steven J. Berman, Joyce A. Korvick, George M. Eliopoulos, Daniel J. Sexton, Thomas G. Slama, John S. Bradley, Jeffrey D. Band, Mary H. White, and Richard D. Meyer

Subjects
Microbiology (medical), medicine.medical_specialty, Infectious Diseases, business.industry, Infectious disease (medical specialty), Family medicine, medicine, business
Published
1997
Full Text
View/download PDF

15. Letters to the Editor

Author

Robyn J. Barst, Alice S. Prince, and Harold C. Neu

Subjects
Pediatrics, Perinatology and Child Health
Abstract

This case report is very encouraging in demonstrating that with recent advancements in echocardiographic technology and clinical perseverance, infective endocarditis (including Aspergillus endocarditis) can be diagnosed by noninvasive techniques. Echocardiography has been helpful in the diagnosis of infective endocarditis (Dillon T, et al: Management of infective endocarditis using echocardiography. J Pediatr 96:552, 1980), although no previous cases of Aspergillus endocarditis diagnosed by echocardiography have been reported. We are hopeful that with continued improvement in M-mode and two-dimensional echocardiographic technology that the necessity for angiocardiographic documentation of suspected vegetations will be eliminated.

Published
1982
Full Text
View/download PDF

16. Rational manipulation of mRNA folding free energy allows rheostat control of pneumolysin production by Streptococcus pneumoniae.

Author

Fábio E Amaral, Dane Parker, Tara M Randis, Ritwij Kulkarni, Alice S Prince, Mimi M Shirasu-Hiza, and Adam J Ratner

Subjects
Medicine, Science
Abstract

The contribution of specific factors to bacterial virulence is generally investigated through creation of genetic "knockouts" that are then compared to wild-type strains or complemented mutants. This paradigm is useful to understand the effect of presence vs. absence of a specific gene product but cannot account for concentration-dependent effects, such as may occur with some bacterial toxins. In order to assess threshold and dose-response effects of virulence factors, robust systems for tunable expression are required. Recent evidence suggests that the folding free energy (ΔG) of the 5' end of mRNA transcripts can have a significant effect on translation efficiency and overall protein abundance. Here we demonstrate that rational alteration of 5' mRNA folding free energy by introduction of synonymous mutations allows for predictable changes in pneumolysin (PLY) expression by Streptococcus pneumoniae without the need for chemical inducers or heterologous promoters. We created a panel of isogenic S. pneumoniae strains, differing only in synonymous (silent) mutations at the 5' end of the PLY mRNA that are predicted to alter ΔG. Such manipulation allows rheostat-like control of PLY production and alters the cytotoxicity of whole S. pneumoniae on primary and immortalized human cells. These studies provide proof-of-principle for further investigation of mRNA ΔG manipulation as a tool in studies of bacterial pathogenesis.

Published
2015
Full Text
View/download PDF

17. Bacterial pathogens activate a common inflammatory pathway through IFNλ regulation of PDCD4.

Author

Taylor S Cohen and Alice S Prince

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

The type III interferon (IFNλ) receptor IL-28R is abundantly expressed in the respiratory tract and has been shown essential for host defense against some viral pathogens, however no data are available concerning its role in the innate immune response to bacterial pathogens. Staphylococcus aureus and Pseudomonas aeruginosa induced significant production of IFNλ in the lung, and clearance of these bacteria from the lung was significantly increased in IL-28R null mice compared to controls. Improved bacterial clearance correlated with reduced lung pathology and a reduced ratio of pro- vs anti-inflammatory cytokines in the airway. In human epithelial cells IFNλ inhibited miR-21 via STAT3 resulting in upregulation of PDCD4, a protein known to promote inflammatory signaling. In vivo 18 hours following infection with either pathogen, miR-21 was significantly reduced and PDCD4 increased in the lungs of wild type compared to IL-28R null mice. Infection of PDCD4 null mice with USA300 resulted in improved clearance, reduced pathology, and reduced inflammatory cytokine production. These data suggest that during bacterial pneumonia IFNλ promotes inflammation by inhibiting miR-21 regulation of PDCD4.

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results