Digital Commons Network^™

Hiv-1 Reactivation Induced By The Periodontal Pathogens Fusobacterium Nucleatum And Porphyromonas Gingivalis Involves Toll-Like Receptor 2 And 9 Activation In Monocytes/Macrophages, Octavio A. Gonzalez, Mengtao Li, Jeffrey L. Ebersole, Chifu B. Huang

Center for Oral Health Research Faculty Publications

Although oral coinfections (e.g., periodontal disease) are highly prevalent in human immunodeficiency virus type 1-positive (HIV-1⁺) patients and appear to positively correlate with viral load levels, the potential for oral bacteria to induce HIV-1 reactivation in latently infected cells has received little attention. We showed that HIV-1 long terminal repeat (LTR) promoter activation can be induced by periodontopathogens in monocytes/macrophages; nevertheless, the mechanisms involved in this response remain undetermined. Since Toll-like receptor 2 (TLR2), TLR4, and TLR9 activation have been involved in HIV-1 recrudescence, we sought to determine the role of these TLRs in HIV-1 reactivation induced by …

A Role For The Histone Deacetylase Hdac4 In The Life-Cycle Of Hiv-1-Based Vectors., Johanna A Smith, Jennifer Yeung, Gary D Kao, René Daniel

Department of Medicine Faculty Papers

HIV-1 integration is mediated by the HIV-1 integrase protein, which joins 3'-ends of viral DNA to host cell DNA. To complete the integration process, HIV-1 DNA has to be joined to host cell DNA also at the 5'-ends. This process is called post-integration repair (PIR). Integration and PIR involve a number of cellular co-factors. These proteins exhibit different degrees of involvement in integration and/or PIR. Some are required for efficient integration or PIR. On the other hand, some reduce the efficiency of integration. Finally, some are involved in integration site selection. We have studied the role of the histone deacetylase …

Cross-Reactivity Of Antibodies Against Leptospiral Recurrent Uveitis-Associated Proteins A And B (Lrua And Lrub) With Eye Proteins, Ashutosh Verma, Pawan Kumar, Kelly Babb, John F. Timoney, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Infection by Leptospira interrogans has been causally associated with human and equine uveitis. Studies in our laboratories have demonstrated that leptospiral lipoprotein LruA and LruB are expressed in the eyes of uveitic horses, and that antibodies directed against LruA and LruB react with equine lenticular and retinal extracts, respectively. These reactivities were investigated further by performing immunofluorescent assays on lenticular and retinal tissue sections. Incubation of lens tissue sections with LruA-antiserum and retinal sections with LruB-antiserum resulted in positive fluorescence. By employing two-dimensional gel analyses followed by immunoblotting and mass spectrometry, lens proteins cross-reacting with LruA antiserum were identified to …

Human Papillomavirus And Survival Of Patients With Oropharyngeal Cancer., K Kian Ang, Jonathan Harris, Richard Wheeler, Randal Weber, David I Rosenthal, Phuc Felix Nguyen-Tân, William H Westra, Christine H Chung, Richard C Jordan, Charles Lu, Harold Kim, Rita S. Axelrod, Md, C Craig Silverman, Kevin P Redmond, Maura L Gillison

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.

METHODS: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive …

Anti-Hiv Activity In Cervical-Vaginal Secretions From Hiv-Positive And -Negative Women Correlate With Innate Antimicrobial Levels And Igg Antibodies, Mimi Ghosh, John V. Fahey, Zheng Shen, Timothy Lahey, Susan Cu-Uvin, Zhijin Wu, Kenneth Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira

Dartmouth Scholarship

Background: We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(2) women on target cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+) and (2) women inhibit HIV infection.

Methodology/Principal Findings: CVL from 32 HIV(+) healthy women with high CD4 counts and 15 healthy HIV(2) women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti- HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and …

Sizing Up Pharmacotherapy For Obesity., Michael A. Valentino, Andre Terzic, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Obesity has increased over the last 20 years, from a condition affecting only a small portion of populations in developed countries, into a global pandemic. The impact of obesity can be appreciated in the context of the populations at risk, and it is estimated that >1 billion adults worldwide are overweight (BMI >25 kg/m2), 300 million of whom are clinically obese (BMI >30 kg/m2). In the United States, 65% of adults are overweight, and 32.2% of them are obese, a prevalence that has doubled over 20 years. In industrialized countries, obesity rates have tripled, coinciding with adoption of a Western …

Enhanced Psychosocial Well-Being Following Participation In A Mindfulness-Based Stress Reduction Program Is Associated With Increased Natural Killer Cell Activity., Carolyn Y Fang, Diane K Reibel, Margaret L Longacre, Steven Rosenzweig, Donald E Campbell, Steven D Douglas

Marcus Institute of Integrative Health Faculty Papers

BACKGROUND: Mindfulness-based stress reduction (MBSR) programs have consistently been shown to enhance the psychosocial well-being of participants. Given the well-established association between psychosocial factors and immunologic functioning, it has been hypothesized that enhanced psychosocial well-being among MBSR participants would be associated with corresponding changes in markers of immune activity.

OBJECTIVES: The objectives of this study were to examine changes in psychosocial and immunologic measures in a heterogeneous patient sample following participation in a MBSR program.

DESIGN: A single-group, pretest/post-test design was utilized.

SETTING: The intervention was conducted at an academic health center.

SUBJECTS: This pilot study involved 24 participants (aged …

An Investigation Of Depression And Fatigue Post West Nile Virus Infection., Patti J Berg, Stacy Smallfield, Lana Svien

Journal Articles: Occupational Therapy

INTRODUCTION: The purpose of this study was to examine depression and fatigue in individuals with a seropositive confirmed history of West Nile virus (WNV) infection.

METHODS: The South Dakota State Epidemiologist sent 218 letters inviting residents with a diagnosis of WNV to participate in the study. Forty-five subjects were tested. An occupational therapist and a physical therapist met with each participant to assess performance parameters, including depression and fatigue levels. Subjects (n=42) completed the Revised Center for Epidemiologic Studies Depression Scale (CES-D) during the assessment. The Modified Fatigue Impact Scale (MFIS) was sent to participants as a follow-up questionnaire, and …

Bone Marrow Stromal Cells Use Tgf-Β To Suppress Allergic Responses In A Mouse Model Of Ragweed-Induced Asthma, K. Nemeth, A. Keane-Myers, J. M. Brown, D. D. Metcalfe, J. D. Gorham

Dartmouth Scholarship

Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC- driven immunomodulation is mediated by the suppression of pro- inflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2- dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of …

A Woman With Hiv Infection, Brain Abscesses, And Eosinophilia, Marcela Campo, Man K Phung, Rehan Ahmed, Paul Cantey, Henry Bishop, Tanvir K Bell, Carolyn Gardiner, Cesar A Arias

Faculty, Staff and Student Publications

No abstract provided.

Recent Diarrhea Is Associated With Elevated Salivary Igg Responses To Cryptosporidium In Residents Of An Eastern Massachusetts Community, A. I. Egorov, L. M. Montuori Trimble, L. Ascolillo, H. D. Ward, Deborah A. Levy, R. D. Morris, E. N. Naumova, J. K. Griffiths

Journal Articles: Epidemiology

BACKGROUND: Serological data suggest that Cryptosporidium infections are common but underreported. The invasiveness of blood sampling limits the application of serology in epidemiological surveillance. We pilot-tested a non-invasive salivary anti-Cryptosporidium antibody assay in a community survey involving children and adults.

MATERIALS AND METHODS: Families with children were recruited in a Massachusetts community in July; symptoms data were collected at 3 monthly follow-up mail surveys. One saliva sample per person (n = 349) was collected via mail, with the last survey in October. Samples were analyzed for IgG and IgA responses to a recombinant C. hominis gp15 sporozoite protein using a …

Vertical Dispersal Of Aedes (Stegomyia) Spp. In High-Rise Apartments In Putrajaya, Malaysia, Othman Wan-Norafikah, Wasi Ahmad Nazni, S. Noramiza, S. Shafa'ar-Ko'ohar, A. Azirol-Hisham, R. Nor-Hafizah, M.G. Sumarni, H. Mohd-Hasrul, Mohd Sofian-Azirun, H.L. Lee

Research Publications (2006 to 2010)

A preliminary study on the vertical dispersal of Aedes populations in high-riseapartments was carried out in Presint 9, Putrajaya, Malaysia. Ovitraps were placed indoorswithin four blocks of high-rise apartments from the ground floors (0.0 – 3.0 m) until upto the tenth floors (28.1 – 30.0 m). Aedes aegypti was the dominant species found in theovitraps (87.85%), while Aedes albopictus was found in lower numbers. From total numberof larvae collected (650), 40.92% of these larvae were obtained from the fourth block;Block D. The peak density of Aedes sp. was observed at level 6 (16.1 – 18.0 m), whileAe. aegypti was found …

Susceptibility Of Field-Collected Aedes Aegypti (L.) (Diptera: Culicidae) To Bacillus Thuringiensis Israelensis And Temephos, S.R. Loke, W.A. Andy-Tan, S. Benjamin, H.L. Lee, Mohd Sofian-Azirun

Research Publications (2006 to 2010)

The susceptibility status of field-collected Aedes aegypti (L.) from a dengue endemic area to Bacillus thuringiensis israelensis (Bti) and temephos was determined. Since August 2007, biweekly ovitrap surveillance (OS) was conducted for 12 mo in 2 sites, A & B, in Shah Alam, Selangor. Site A was treated with a Bti formulation, VectoBac® WG at 500 g/ha, from December 2007 - June 2008 while Site B was subjected to routine dengue vector control activities conducted by the local municipality. Aedes aegypti larvae collected from OS in both sites were bred until F3 and evaluated for their susceptibility. The larvae were …

The Relationship Between Mosquito Abundance And Rice Field Density In The Republic Of Korea, Erin E. Richards, Penny Masuoka, David Brett-Major, Matthew Smith, Terry A. Klein, Heung Chul Kim, Assaf Anyamba, John Grieco

Journal Articles: Epidemiology

BACKGROUND: Japanese encephalitis virus (JEV), the causative agent of Japanese encephalitis (JE), is endemic to the Republic of Korea (ROK) where unvaccinated United States (U.S.) military Service members, civilians and family members are stationed. The primary vector of the JEV in the ROK is Culex tritaeniorhynchus. The ecological relationship between Culex spp. and rice fields has been studied extensively; rice fields have been shown to increase the prevalence of Cx. tritaeniorhynchus. This research was conducted to determine if the quantification of rice field land cover surrounding U.S. military installations in the ROK should be used as a parameter in a …

Impact Of Empire Expansion On Household Diet: The Inka In Northern Chile's Atacama Desert, Sheila Dorsey Vinton, Linda Perry, Karl J. Reinhard, Calogero M. Santoro, Isabel Teixeira-Santos

Anthropology Faculty Publications

The impact of expanding civilization on the health of American indigenous societies has long been studied. Most studies have focused on infections and malnutrition that occurred when less complex societies were incorporated into more complex civilizations. The details of dietary change, however, have rarely been explored. Using the analysis of starch residues recovered from coprolites, here we evaluate the dietary adaptations of indigenous farmers in northern Chile's Atacama Desert during the time that the Inka Empire incorporated these communities into their economic system. This system has been described as "complementarity" because it involves interaction and trade in goods produced at …

Brazilian Adolescents Infected By Hiv: Epidemiologic Characteristics And Adherence To Treatment, Julia K. C. Machado, Maria J. C. Sant'anna, Veronica Coates, Flavia J. Almeida, Eitan N. Berezin, Hatim A. Omar

Pediatrics Faculty Publications

Over the last 3 decades since the first AIDS cases appeared, we have witnessed great progress in therapeutic methodologies that have transformed the evolution of the disease from debilitating and fatal, into chronic and controllable. HIV-infected children are arriving at adolescence and bringing specific challenges, not only to themselves, but also to their families and caregivers. This retrospective study sets forth epidemiological and treatment characteristics of 46 HIV-infected adolescents followed in a specialized university service relating said characteristics to therapy adherence assessed through a combination of three indirect methods. Therapy adherence did not reveal any association with either epidemiologic characteristics …

Aging Influences The Neural Correlates Of Lexical Decision But Not Automatic Semantic Priming, Brian T. Gold, Anders H. Andersen, Greg A. Jicha, Charles D. Smith

Neuroscience Faculty Publications

Human behavioral data indicate that older adults are slower to perform lexical decisions (LDs) than young adults but show similar reaction time gains when these decisions are primed semantically. The present study explored the functional neuroanatomic bases of these frequently observed behavioral findings. Young and older groups completed unprimed and primed LD tasks while functional magnetic resonance imaging (fMRI) was recorded, using a fully randomized trial design paralleling those used in behavioral research. Results from the unprimed task found that age-related slowing of LD was associated with decreased activation in perceptual extrastriate regions and increased activation in regions associated with …

Development Of A Mouse Monoclonal Antibody Cocktail For Post-Exposure Rabies Prophylaxis In Humans., Thomas Müller, Bernhard Dietzschold, Hildegund Ertl, Anthony R Fooks, Conrad Freuling, Christine Fehlner-Gardiner, Jeannette Kliemt, Francois X Meslin, Charles E Rupprecht, Noël Tordo, Alexander I Wanderler, Marie Paule Kieny

Department of Microbiology and Immunology Faculty Papers

As the demand for rabies post-exposure prophylaxis (PEP) treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG) has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb) cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used …

Adherence To Host Extracellular Matrix And Serum Components By Enterococcus Faecium Isolates Of Diverse Origin, Meng Zhao, Jouko Sillanpää, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecium has emerged as an important cause of nosocomial infections over the last two decades. We recently demonstrated collagen type I (CI) as a common adherence target for some E. faecium isolates and a significant correlation was found to exist between acm-mediated CI adherence and clinical origin. Here, we evaluated 60 diverse E. faecium isolates for their adherence to up to 15 immobilized host extracellular matrix and serum components. Adherence phenotypes were most commonly observed to fibronectin (Fn) (20% of the 60 isolates), fibrinogen (17%) and laminin (Ln) (13%), while only one or two of the isolates adhered to …

High Content Screening Identifies Decaprenyl-Phosphoribose 2’ Epimerase As A Target For Intracellular Antimycobacterial Inhibitors, Thierry Christophe, Mary Jackson, Hee Kyoung Jeon, Denis Fenistein, Monica Contreras-Dominguez, Jaeseung Kim, Auguste Genovesio, Jean-Philippe Carralot, Fanny Ewann, Eun Hye Kim, Sae Yeon Lee, Sunhee Kang, Min Jung Seo, Eun Jung Park, Henrieta Skovierová, Ha Pham, Giovanna Riccardi, Ji Youn Nam, Laurent Marsollier, Marie Kempf, Marie-Laure Joly-Guillou, Taegwon Oh, Won Kyung Shin, Zaesung No, Ulf Nehrbass, Roland Brosch, Stewart T. Cole

Faculty and Staff Publications

A critical feature of Mycobacterium tuberculosis, the causative agent of human tuberculosis (TB), is its ability to survive and multiply within macrophages, making these host cells an ideal niche for persisting microbes. Killing the intracellular tubercle bacilli is a key requirement for efficient tuberculosis treatment, yet identifying potent inhibitors has been hampered by labor-intensive techniques and lack of validated targets. Here, we present the development of a phenotypic cell-based assay that uses automated confocal fluorescence microscopy for high throughput screening of chemicals that interfere with the replication of M. tuberculosis within macrophages. Screening a library of 57,000 small molecules led …

The Medicine Wheel Nutrition Intervention: A Diabetes Education Study With The Cheyenne River Sioux Tribe, Kendra K. Kattelmann, Kibbe Conti, Cuirong Ren

Health and Nutritional Sciences Faculty Publications

OBJECTIVE: The Northern Plains Indians of the Cheyenne River Sioux Tribe have experienced significant lifestyle and dietary changes over the past seven generations that have resulted in increased rates of diabetes and obesity. The objective of this study was to determine if Northern Plains Indians with type 2 diabetes mellitus who are randomized to receive culturally adapted educational lessons based on the Medicine Wheel Model for Nutrition in addition to their usual dietary education will have better control of their type 2 diabetes than a nonintervention, usual care group who received only the usual dietary education from their personal providers. …

Epidemiology And Outcomes Of Candidemia In 2019 Patients: Data From The Prospective Antifungal Therapy Alliance Registry., David L Horn, Dionissios Neofytos, Elias J Anaissie, Jay A Fishman, William J Steinbach, Ali J Olyaei, Kieren A Marr, Michael A Pfaller, Chi-Hsing Chang, Karen M Webster

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing.

METHODS: Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis.

RESULTS: The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher …

Hiv Policy: The Path Forward--A Joint Position Paper Of The Hiv Medicine Association Of The Infectious Diseases Society Of America And The American College Of Physicians., Christine Lubinski, Judith Aberg, Arlene D Bardeguez, Richard Elion, Patricia Emmanuel, Daniel Kuritzkes, Michael Saag, Kathleen E Squires, Andrea Weddle, Jennifer Rainey, M Renee Zerehi, J Fred Ralston, David A Fleming, David Bronson, Molly Cooke, Charles Cutler, Yul Ejnes, Robert Gluckman, Mark Liebow, Kenneth Musana, Mark E Mayer, Mark W Purtle, P Preston Reynolds, Lavanya Viswanathan, Kevin B Weiss, Baligh Yehia

Department of Medicine Faculty Papers

Executive Summary

The American College of Physicians (ACP) and the Infectious Diseases Society of America (IDSA) have jointly published 3 policy statements on AIDS, the first in 1986 [1], the second in 1988 [2], and the third in 1994 [3]. In 2001, the IDSA created the HIV Medicine Association (HIVMA), and this updated policy paper is a collaboration between the ACP and the HIVMA of the IDSA. Since the last statement, many new developments call for the need to reexamine and update our policies relating to HIV infection. First, there have been major advances …

A Novel Codon Insert In Protease Of Clade B Hiv Type 1., Parris S Jordan, Art Poon, Joseph Eron, Kathleen Squires, Caroline Ignacio, Douglas D Richman, Davey M Smith

Division of Infectious Diseases and Environmental Medicine Faculty Papers

A novel combination of three codon inserts in the pol coding region of HIV-1 RNA was identified in a highly antiretroviral experienced study subject with HIV-1 infection. A one codon insert was observed in the protease region between codon 40 and 41 simultaneously with a two codon insert present in the reverse transcriptase region at codon 69.

The Physician's Response To Climate Change., Mona Sarfaty, Safiya Abouzaid

Department of Family & Community Medicine Faculty Papers

Climate change will have an effect on the health and well-being of the populations cared for by practicing physicians. The anticipated medical effects include heat- and cold-related deaths, cardiovascular illnesses, injuries and mental harms from extreme weather events, respiratory illnesses caused by poor air quality, infectious diseases that emanate from contaminated food, water, or spread of disease vectors, the injuries caused by natural disasters, and the mental harm associated with social disruption. Within several years, such medical problems are likely to reach the doorsteps of many physicians. In the face of this reality, physicians should assume their traditional roles as …

Plant Vaccines: An Immunological Perspective., Douglas C. Hooper

Department of Cancer Biology Faculty Papers

The advent of technologies to express heterologous proteins in planta has led to the proposition that plants may be engineered to be safe, inexpensive vehicles for the production of vaccines and possibly even vectors for their delivery. The immunogenicity of a variety of antigens of relevance to vaccination expressed in different plants has been assessed. The purpose of this article is to examine the utility of plant-expression systems in vaccine development from an immunological perspective.

A Study Of Micrornas In Silico And In Vivo: Diagnostic And Therapeutic Applications In Cancer., Scott A Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is emerging evidence of the production in human tumors of abnormal levels of microRNAs (miRNAs), which have been assigned oncogenic and/or tumor-suppressor functions. While some miRNAs commonly exhibit altered amounts across tumors, more often, different tumor types produce unique patterns of miRNAs, related to their tissue of origin. The role of miRNAs in tumorigenesis underscores their value as mechanism-based therapeutic targets in cancer. Similarly, unique patterns of altered levels of miRNA production provide fingerprints that may serve as molecular biomarkers for tumor diagnosis, classification, prognosis of disease-specific outcomes and prediction of therapeutic responses.

Drug Abuse Treatment Beyond Prison Walls, Carl Leukefeld, Carrie B. Oser, Jennifer Havens, Michele Staton Tindall, Jennifer Mooney, Jamieson B. Duvall, Hannah Knudsen

Behavioral Science Faculty Publications

The period surrounding release from prison is a critical time for parolees, bearing the potential for a drug-free and crime-free life in the community but also high risks for recidivism and relapse to drugs. The authors describe two projects. The first illustrates the use of a formal Delphi process to elicit and combine the expertise of treatment providers, researchers, corrections personnel, and other stakeholders in a set of statewide guidelines for facilitating re-entry. The second project is a six-session intervention to enable women to protect themselves against acquiring or transmitting HIV in their intimate relationships.

Associated Symptoms In The Ten Days Before Diagnosis Of Kawasaki Disease., Annette L. Baker, Minmin Lu, L Luann Minich, Andrew M. Atz, Gloria L. Klein, Rosalind Korsin, Linda Lambert, Jennifer S. Li, Wilbert Mason, Elizabeth Radojewski, Victoria L. Vetter, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To describe common associated symptoms within the 10 days before diagnosis in subjects enrolled in the Pediatric Heart Network's trial of steroid therapy in Kawasaki disease (KD).

STUDY DESIGN: Patients with acute KD were enrolled between days 4 and 10 of illness at 8 centers between 2002 and 2004. We defined common associated symptoms as those occurring in >or=10% of patients. Principal clinical criteria for KD were not included in this analysis.

RESULTS: Among 198 patients, irritability was reported in 98 (50%), vomiting in 88 (44%), decreased food/fluid intake in 73 (37%), cough in 55 (28%), diarrhea in 52 …

Long-Distance Delivery Of Bacterial Virulence Factors By Pseudomonas Aeruginosa Outer Membrane Vesicles, Jennifer M. Bomberger, Daniel P. Maceachran, Bonita A. Coutermarsh, Siying Ye, George A. O'Toole, Bruce A. Stanton, Frederick M. Ausubel

Dartmouth Scholarship

Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report a mechanism for the long-distance delivery of multiple bacterial virulence factors, simultaneously and directly into the host cell cytoplasm, thus obviating the need for direct interaction of the pathogen with the host cell to cause cytotoxicity. We show that outer membrane–derived vesicles (OMV) secreted by the opportunistic human pathogen Pseudomonas aeruginosa deliver multiple virulence factors, including β-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif, directly into the host cytoplasm via fusion of OMV with lipid rafts in the host plasma …