Digital Commons Network^™

Recent Incarceration, Substance Use, Overdose, And Service Use Among People Who Use Drugs In Rural Communities, Daniel B. Hoover, P. Todd Korthuis, Elizabeth Needham Waddell, Canyon Foot, Caitlin Conway, Heidi M. Crane, Peter D. Friedmann, Vivian F. Go, Mai T. Pho, Milan F. Satcher, Adams Sibley, Ryan P. Westergaard, April M. Young, Ryan Cook

Dartmouth Scholarship

Importance Drug use and incarceration have a substantial impact on rural communities, but factors associated with the incarceration of rural people who use drugs (PWUD) have not been thoroughly investigated.

Objective To characterize associations between recent incarceration, overdose, and substance use disorder (SUD) treatment access among rural PWUD.

Design, Setting, and Participants For this cross-sectional study, the Rural Opioid Initiative research consortium conducted a survey in geographically diverse rural counties with high rates of overdose across 10 US states (Illinois, Wisconsin, North Carolina, Oregon, Kentucky, West Virginia, Ohio, Massachusetts, New Hampshire, and Vermont) between January 25, 2018, and March 17, …

The Feasibility And Utility Of Harnessing Digital Health To Understand Clinical Trajectories In Medication Treatment For Opioid Use Disorder: D-Tect Study Design And Methodological Considerations, Lisa A. Marsch, Ching-Hua Chen, Sara R. Adams, Asma Asyyed, Monique B. Does, Saeed Hassanpour, Emily Hichborn, Melanie Jackson-Morris, Nicholas C. Jacobson, Heather K. Jones, David Kotz, Chantal A. Lambert-Harris, Zhiguo Li, Bethany Mcleman, Varun Mishra, Catherine Stanger, Geetha Subramaniam, Weiyi Wu, Cynthia I. Campbell

Dartmouth Scholarship

Introduction: Across the U.S., the prevalence of opioid use disorder (OUD) and the rates of opioid overdoses have risen precipitously in recent years. Several effective medications for OUD (MOUD) exist and have been shown to be life-saving. A large volume of research has identified a confluence of factors that predict attrition and continued substance use during substance use disorder treatment. However, much of this literature has examined a small set of potential moderators or mediators of outcomes in MOUD treatment and may lead to over-simplified accounts of treatment non-adherence. Digital health methodologies offer great promise for capturing intensive, longitudinal ecologically-valid …

Genomic Epidemiology Of Methicillin-Resistant And -Susceptible Staphylococcus Aureus From Bloodstream Infections, Joshua T. Smith, Elissa M. Eckhardt, Nicole B. Hansel, Tahmineh Rahmani Eliato, Isabella W. Martin, Cheryl P. Andam

Dartmouth Scholarship

Background: Bloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality. Methods: We generated high quality draft genomes from 323 S. aureus blood culture isolates from patients diagnosed with bloodstream infection at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA in 2010–2018. Results: In silico detection of antimicrobial resistance genes revealed that 133/323 isolates (41.18%) carry horizontally acquired genes conferring resistance to at least three antimicrobial classes, with resistance determinants for aminoglycosides, beta-lactams …

Γδ T Cell Ifnγ Production Is Directly Subverted By Yersinia Pseudotuberculosis Outer Protein Yopj In Mice And Humans, Timothy H. Chu, Camille Khairallah, Jason Shieh, Rhea Cho, Zhijuan Qiu, Yue Zhang, Onur Eskiocak, David G. Thanassi, Mark H. Kaplan, Semir Beyaz, Vincent W. Yang, James B. Bliska, Brian S. Sheridan

Dartmouth Scholarship

Yersinia pseudotuberculosis is a foodborne pathogen that subverts immune function by translocation of Yersinia outer protein (Yop) effectors into host cells. As adaptive γδ T cells protect the intestinal mucosa from pathogen invasion, we assessed whether Y. pseudotuberculosis subverts these cells in mice and humans. Tracking Yop translocation revealed that the preferential delivery of Yop effectors directly into murine Vγ4 and human Vδ2+ T cells inhibited anti-microbial IFNγ production. Subversion was mediated by the adhesin YadA, injectisome component YopB, and translocated YopJ effector. A broad anti-pathogen gene signature and STAT4 phosphorylation levels were inhibited by translocated YopJ. Thus, Y. pseudotuberculosis …

Model Systems To Study The Chronic, Polymicrobial Infections In Cystic Fibrosis: Current Approaches And Exploring Future Directions, George A. O’Toole, Aurélie Crabbé, Rolf Kümmerli, John J. Lipuma, Jennifer M. Bomberger, Jane C. Davies, Dominique Limoli, Vanessa V. Phelan, James B. Bliska, William H. Depas, Lars E. Dietrich, Thomas H. Hampton, Ryan Hunter, Cezar M. Khursigara, Alexa Price-Whelan, Alix Ashare, Robert A. Cramer, Joanna B. Goldberg, Freya Harrison, Deborah A. Hogan

Dartmouth Scholarship

A recent workshop titled “Developing Models to Study Polymicrobial Infections,” sponsored by the Dartmouth Cystic Fibrosis Center (DartCF), explored the development of new models to study the polymicrobial infections associated with the airways of persons with cystic fibrosis (CF). The workshop gathered 351 investigators over two virtual sessions. Here, we present the findings of this workshop, summarize some of the challenges involved with developing such models, and suggest three frameworks to tackle this complex problem. The frameworks proposed here, we believe, could be generally useful in developing new model systems for other infectious diseases. Developing and validating new approaches to …

The Relationship Between Central Auditory Tests And Neurocognitive Domains In Adults Living With Hiv, Christopher E. Niemczak, Jonathan D. Lichtenstein, Albert Magohe, Jennifer T. Amato, Abigail M. Fellows, Jiang Gui, Michael Huang, Catherine C. Rieke, Enica R. Massawe, Michael J. Boivin, Ndeserua Moshi, Jay C. Buckey

Dartmouth Scholarship

Objective: Tests requiring central auditory processing, such as speech perception-in-noise, are simple, time efficient, and correlate with cognitive processing. These tests may be useful for tracking brain function. Doing this effectively requires information on which tests correlate with overall cognitive function and specific cognitive domains. This study evaluated the relationship between selected central auditory focused tests and cognitive domains in a cohort of normal hearing adults living with HIV and HIV– controls. The long-term aim is determining the relationships between auditory processing and neurocognitive domains and applying this to analyzing cognitive function in HIV and other neurocognitive disorders longitudinally. Method: …

The Crossroads Of Glycoscience, Infection, And Immunology, Tanya R. Mckitrick, Margaret E. Ackerman, Robert M. Anthony, Clay S. Bennett, Michael Demetriou, Gregory A. Hudalla, Katharina Ribbeck, Stefan Ruhl, Christina M. Woo, Loretta Yang, Seth J. Zost, Ronald L. Schnaar, Tamara L. Doering

Dartmouth Scholarship

Advances in experimental capabilities in the glycosciences offer expanding opportunities for discovery in the broad areas of immunology and microbiology. These two disciplines overlap when microbial infection stimulates host immune responses and glycan structures are central in the processes that occur during all such encounters. Microbial glycans mediate host-pathogen interactions by acting as surface receptors or ligands, functioning as virulence factors, impeding host immune responses, or playing other roles in the struggle between host and microbe. In the context of the host, glycosylation drives cell–cell interactions that initiate and regulate the host response and modulates the effects of antibodies and …

Government Royalties On Sales Of Pharmaceutical And Other Biomedical Products Developed With Substantial Public Funding: Illustrated With The Technology Transfer Of The Drug-Eluting Coronary Stent, Robert S. Danziger, John T. Scott

Dartmouth Scholarship

This study develops a detailed description of the successful technology transfer of an invention—the drug-eluting coronary stent—originating in intramural research within the National Institutes of Health. The history of the commercialization of the invention is used to illustrate a new policy, proposed and explained in this study, for the payment to the government of royalties on the sales of biomedical products developed with substantial public funding provided through indirect as well as direct funding avenues. The proposed policy addresses concerns about the high prices that taxpayers as consumers pay for biomedical products that were developed with funding from the taxpayers …

Determining Levers Of Cost-Effectiveness For Screening Infants At High Risk For Peanut Sensitization Before Early Peanut Introduction, Matthew Greenhawt, Marcus Shaker

Dartmouth Scholarship

Importance Early peanut introduction reduces the risk of developing peanut allergy, especially in high-risk infants. Current US recommendations endorse screening but are not cost-effective relative to other international strategies.

Objective To identify scenarios in which current early peanut introduction guidelines would be cost-effective.

Design, Setting, and Participants This simulation/cohort economic evaluation used microsimulations and cohort analyses in a Markov model to evaluate the cost-effectiveness of early peanut introduction with and without peanut skin prick test (SPT) screening in high-risk infants during an 80-year horizon from a societal perspective. Data were analyzed from April to May 2019.

Exposures High-risk infants with …

Architecting A System Model For Personalized Healthcare Delivery And Managed Individual Health Outcomes, Inas S. Khayal, Amro M. Farid

Dartmouth Scholarship

In recent years, healthcare needs have shifted from treating acute conditions to meeting an unprecedented chronic disease burden. The healthcare delivery system has structurally evolved to address two primary features of acute care: the relatively short time period, on the order of a patient encounter, and the siloed focus on organs or organ systems, thereby operationally fragmenting and providing care by organ specialty. Much more so than acute conditions, chronic disease involves multiple health factors with complex interactions between them over a prolonged period of time necessitating a healthcare delivery model that is personalized to achieve individual health outcomes. Using …

Small Rna Teg49 Is Derived From A Sara Transcript And Regulates Virulence Genes Independent Of Sara In Staphylococcus Aureus, Adhar Manna, Samin Kim, Liviu Cengher, Anna Corvaglia, Stefano Leo, Patrice Francois, Ambrose L. Cheung

Dartmouth Scholarship

Expression of virulence factors in Staphylococcus aureus is regulated by a wide range of transcriptional regulators, including proteins and small RNAs (sRNAs), at the level of transcription and/or translation. The sarA locus consists of three overlapping transcripts generated from three distinct promoters, all containing the sarA open reading frame (ORF). The 5= untranslated regions (UTRs) of these transcripts contain three separate regions 711, 409, and 146 nucleotides (nt) upstream of the sarA translation start, the functions of which remain unknown. Re- cent transcriptome-sequencing (RNA-Seq) analysis and subsequent characterization indicated that two sRNAs, teg49 and teg48, are processed and likely produced …

Safety And Immunogenicity Of An Inactivated Whole Cell Tuberculosis Vaccine Booster In Adults Primed With Bcg: A Randomized, Controlled Trial Of Dar-901, C. Fordham Von Reyn, Timothy Lahey, Robert D. Arbeit, Bernard Landry, Leway Kailani, Lisa Adams, Brenda Haynes, Todd Mackenzie, Wendy Wieland-Alter, Ruth Connor, Sue Tvaroha, David Hokey, Ann Ginsberg, Richard Waddell

Dartmouth Scholarship

Development of a tuberculosis vaccine to boost BCG is a major international health priority. SRL172, an inactivated whole cell booster derived from a non-tuberculous mycobacterium, is the only new vaccine against tuberculosis to have demonstrated efficacy in a Phase 3 trial. In the present study we sought to determine if a three-dose series of DAR-901 manufactured from the SRL172 master cell bank by a new, scalable method was safe and immunogenic.

Aspergillus Fumigatus Trehalose-Regulatory Subunit Homolog Moonlights To Mediate Cell Wall Homeostasis Through Modulation Of Chitin Synthase Activity, Arsa Thammahong, Alayna K. Caffrey-Card, Sourabh Dhingra, Joshua J. Obar, Robert Cramer

Dartmouth Scholarship

Trehalose biosynthesis is found in fungi but not humans. Proteins involved in trehalose biosynthesis are essential for fungal pathogen virulence in humans and plants through multiple mechanisms. Loss of canonical trehalose biosynthesis genes in the human pathogen Aspergillus fumigatus significantly alters cell wall structure and integrity, though the mechanistic link between these virulence-associated pathways remains enigmatic. Here we characterize genes, called tslAand tslB, which encode proteins that contain domains similar to those corresponding to trehalose-6-phosphate phosphatase but lack critical catalytic residues for phosphatase activity. Loss of tslA reduces trehalose content in both conidia and mycelia, impairs cell wall …

Epidemiology Of 45,616 Suspect Cases Of Hand, Foot And Mouth Disease In Chongqing, China, 2011–2015, Jian Tao, Xiao-Yan He, Yu Shi, Guohun Zhu, Shan Liu, Zhenzhen Zhang, Shi Tang, Rong Zhang, Bin Peng, Zhidai Liu, Junjie Tan, Qian Chen, Xingbin Wang, Liming Bao, Lin Zou, Penghui Zhang

Dartmouth Scholarship

Epidemiology and etiology of hand, foot, and mouth disease (HFMD) based on large sample size or evaluation of detection for more enterovirus serotypes are not well investigated in Chongqing of China. 45,616 suspect HFMD patients were prospectively enrolled among whom 21,615 were laboratory confirmed HFMD cases over a 5-year period (January 2011 to December 2015). Their epidemiological, clinical, and laboratory data were extracted and stratified by month, age, sex, disease severity, and enterovirus serotype. Subsequently 292 non-EV-A71/CV-A16 HFMD confirmed cases were randomly selected in three consecutive outbreaks to detect CV-A6 and CV-A10, using RT-PCR. Results showed that the HFMD epidemic …

Filamentous Fungal Carbon Catabolite Repression Supports Metabolic Plasticity And Stress Responses Essential For Disease Progression, Sarah R. Beattie, Kenneth Mark, Arsa Thammahong, Laure Nicolas Annick Ries, Sourabh Dhingra, Alayna Caffrey-Carr, Chao Cheng

Dartmouth Scholarship

Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A. fumigatus requires a carbon catabolite repression (CCR) mediated genetic network to support in vivo fungal fitness and disease progression. While CCR as mediated by the transcriptional repressor CreA is …

Production Of Putative Enhanced Oral Cholera Vaccine Strains That Express Toxin-Coregulated Pilus, Caitlyn A. Hauke, Ronald K. Taylor

Dartmouth Scholarship

The use of whole cell killed (WCK) oral cholera vaccines is an important strategy for cholera prevention in endemic areas. To overcome current vaccine limitations, we engineered strains of V. cholerae to be non-toxigenic and to express the protective protein colonization factor, toxin-coregulated pilus (TCP), under scale-up conditions potentially amenable to vaccine production. Two V. cholerae clinical strains were selected and their cholera toxin genes deleted. The tcp operon was placed under control of a rhamnose-inducible promoter. Production and stability of TCP were assessed under various conditions. The strains lack detectable cholera toxin production. The addition of 0.1% …

Tenofovir Inhibits Wound Healing Of Epithelial Cells And Fibroblasts From The Upper And Lower Human Female Reproductive Tract, Marta Rodriguez-Garcia, Mickey V. Patel, Zheng Shen, Jack Bodwell, Richard M. Rossol, Charles R. Wira

Dartmouth Scholarship

Disruption of the epithelium in the female reproductive tract (FRT) is hypothesized to increase HIV infection risk by interfering with barrier protection and facilitating HIV-target cell recruitment. Here we determined whether Tenofovir (TFV), used vaginally in HIV prevention trials, and Tenofovir alafenamide (TAF), an improved prodrug of TFV, interfere with wound healing in the human FRT. TFV treatment of primary epithelial cells and fibroblasts from the endometrium (EM), endocervix (CX) and ectocervix (ECX) significantly delayed wound closure. Reestablishment of tight junctions was compromised in EM and CX epithelial cells even after wound closure occurred. In contrast, TAF had no inhibitory …

A New Class Of Inhibitors Of The Arac Family Virulence Regulator Vibrio Cholerae Toxt, Anne K. Woodbrey, Evans O. Onyango, Maria Pellegrini, Gabriela Kovacikova, Ronald Taylor, Gordon Gribble, F. Jon Kull

Dartmouth Scholarship

Vibrio cholerae is responsible for the diarrheal disease cholera that infects millions of people worldwide. While vaccines protecting against cholera exist, and oral rehydration therapy is an effective treatment method, the disease will remain a global health threat until long-term solutions such as improved sanitation and access to clean water become widely available. Because of this, there is a pressing need for potent therapeutics that can either mitigate cholera symptoms, or act prophylactically to prevent the virulent effects of a cholera infection. Here we report the design, synthesis, and characterization of a set of compounds that bind and inhibit ToxT, …

Dueling Biological And Social Contagions, Feng Fu, Nicholas A. Christakis, James H. Fowler

Dartmouth Scholarship

Numerous models explore how a wide variety of biological and social phenomena spread in social networks. However, these models implicitly assume that the spread of one phenomenon is not affected by the spread of another. Here, we develop a model of “dueling contagions”, with a particular illustration of a situation where one is biological (influenza) and the other is social (flu vaccination). We apply the model to unique time series data collected during the 2009 H1N1 epidemic that includes information about vaccination, flu, and face-to-face social networks. The results show that well- connected individuals are more likely to get vaccinated, …

Boosting Of Hiv Envelope Cd4 Binding Site Antibodies With Long Variable Heavy Third Complementarity Determining Region In The Randomized Double Blind Rv305 Hiv-1 Vaccine Trial, David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman

Dartmouth Scholarship

The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1- uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 …

Potent Single-Domain Antibodies That Arrest Respiratory Syncytial Virus Fusion Protein In Its Prefusion State, Iebe Rossey, Morgan Gilman, Stephanie Kabeche, Koen Sedeyn, Daniel Wrapp

Dartmouth Scholarship

Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs …

Social Determinants Of Conspiratorial Ideation, Joseph Digrazia

Dartmouth Scholarship

Scholars have recently become increasingly interested in understanding the prevalence and persistence of conspiratorial beliefs among the public as recent research has shown such beliefs to be both widespread and to have deleterious effects on the political process. This article seeks to develop a sociological understanding of the structural conditions that are associated with conspiratorial belief. Using aggregate Google search data to measure public interest in two popular political conspiracy theories, the findings indicate that social conditions associated with threat and insecurity, including unemployment, changes in partisan control of government, and demographic changes, are associated with increased conspiratorial ideation.

Implementation Research On Community Health Workers’ Provision Of Maternal And Child Health Services In Rural Liberia, Peter W. Luckow, Avi Kenny, Emily White, Madeleine Ballard, Lorenzo Dorr, Kirby Erlandson, Benjamin Grant, Alice Johnson, Breanna Lorenzen, Subarna Mukherjee

Dartmouth Scholarship

OBJECTIVE:

To assess changes in the use of essential maternal and child health services in Konobo, Liberia, after implementation of an enhanced community health worker (CHW) programme.

METHODS:

The Liberian Ministry of Health partnered with Last Mile Health, a nongovernmental organization, to implement a pilot CHW programme with enhanced recruitment, training, supervision and compensation. To assess changes in maternal and child health-care use, we conducted repeated cross-sectional cluster surveys before (2012) and after (2015) programme implementation.

FINDINGS:

Between 2012 and 2015, 54 CHWs, seven peer supervisors and three clinical supervisors were trained to serve a population of 12 127 people …

Regulation Of Sterol Biosynthesis In The Human Fungal Pathogen Aspergillus Fumigatus: Opportunities For Therapeutic Development, Sourabh Dhingra, Robert A. Cramer

Dartmouth Scholarship

Sterols are a major component of eukaryotic cell membranes. For human fungal infections caused by the filamentous fungus Aspergillus fumigatus, antifungal drugs that target sterol biosynthesis and/or function remain the standard of care. Yet, an understanding of A. fumigatus sterol biosynthesis regulatory mechanisms remains an under developed therapeutic target. The critical role of sterol biosynthesis regulation and its interactions with clinically relevant azole drugs is highlighted by the basic helix loop helix (bHLH) class of transcription factors known as Sterol Regulatory Element Binding Proteins (SREBPs). SREBPs regulate transcription of key ergosterol biosynthesis genes in fungi including A. fumigatus. …

Streptomyces Exploration Is Triggered By Fungal Interactions And Volatile Signals, Stephanie E. Jones, Louis Ho, Christiaan A. Rees, Jane E. Hill, Justin R. Nodwell, Marie A. Elliot

Dartmouth Scholarship

It has long been thought that the life cycle of Streptomyces bacteria encompasses three developmental stages: vegetative hyphae, aerial hyphae and spores. Here, we show interactions between Streptomyces and fungi trigger a previously unobserved mode of Streptomyces development. We term these Streptomyces cells ‘explorers’, for their ability to adopt a non-branching vegetative hyphal conformation and rapidly transverse solid surfaces. Fungi trigger Streptomyces exploratory growth in part by altering the composition of the growth medium, and Streptomyces explorer cells can communicate this exploratory behaviour to other physically separated streptomycetes using an airborne volatile organic compound (VOC). These results reveal that interkingdom …

Streptococcus Pneumoniae Intracranial Abscess And Post-Infectious Vasculitis, Alexandra Lucas, Ko Ko Maung, Ryan Ratts

Dartmouth Scholarship

Intracranial abscesses are rare complications of Streptococcus pneumoniae infections, and to our knowledge, there have been no case reports of post-infectious vasculitis developing in such patients. Here we describe the case of a 48-year-old post-splenectomy male who developed post-infectious vasculitis following S. pneumoniae otitis media complicated by mastoiditis, osteomyelitis, meningitis, and intracranial abscess. Clinicians ought to be aware of the possible adverse outcomes of invasive S. pneumoniae and the limitations of current treatment options.

Immunogenicity And Protective Efficacy Of The Dar-901 Booster Vaccine In A Murine Model Of Tuberculosis, Timothy Lahey, Dominick Laddy, Krystal Hill, Jacqueline Schaeffer

Dartmouth Scholarship

The development of a novel tuberculosis vaccine is a leading global health priority. SRL172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase III trial in HIV-infected and BCG immunized adults in Tanzania. Here we describe the immunogenicity and protective efficacy of DAR-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.

The Vibrio Cholerae Minor Pilin Tcpb Initiates Assembly And Retraction Of The Toxin-Coregulated Pilus, Dixon Ng, Tony Harn, Tuba Altindal, Subramania Kolappan, Jarrad Marles, Rajan Lala, Ingrid Spielman, Yang Gao, Caitlyn Hauke, Gabriela Kovacikova

Dartmouth Scholarship

Type IV pilus (T4P) systems are complex molecular machines that polymerize major pilin proteins into thin filaments displayed on bacterial surfaces. Pilus functions require rapid extension and depolymerization of the pilus, powered by the assembly and retraction ATPases, respectively. A set of low abundance minor pilins influences pilus dynamics by unknown mechanisms. The Vibrio cholerae toxin-coregulated pilus (TCP) is among the simplest of the T4P systems, having a single minor pilin TcpB and lacking a retraction ATPase. Here we show that TcpB, like its homolog CofB, initiates pilus assembly. TcpB co-localizes with the pili but at extremely low levels, equivalent …

Signaling Through Lrg1, Rho1 And Pkc1 Governs Candida Albicans Morphogenesis In Response To Diverse Cues, Jinglin L. Xie, Nora Grahl, Trevor Sless, Michelle Leach, Sang Hu Kim, Deborah Hogan

Dartmouth Scholarship

The capacity to transition between distinct morphological forms is a key virulence trait for diverse fungal pathogens. A poignant example of a leading opportunistic fungal pathogen of humans for which an environmentally responsive developmental program underpins virulence is Candida albicans. C. albicans mutants that are defective in the transition between yeast and filamentous forms typically have reduced virulence. Although many positive regulators of C. albicans filamentation have been defined, there are fewer negative regulators that have been implicated in repression of filamentation in the absence of inducing cues. To discover novel negative regulators of filamentation, we screened …

Use Of A Multiplex Transcript Method For Analysis Of Pseudomonas Aeruginosa Gene Expression Profiles In The Cystic Fibrosis Lung, Alex H. Gifford, Sven D. Willger, Emily L. Dolben, Lisa A. Moulton, Dana Dorman, Heather Bean, Jane Hill, Thomas Hampton, Alix Ashare, Deborah Hogan

Dartmouth Scholarship

The discovery of therapies that modulate Pseudomonas aeruginosa virulence or that can eradicate chronic P. aeruginosa lung infections associated with cystic fibrosis (CF) will be advanced by an improved understanding of P. aeruginosa behavior in vivo We demonstrate the use of multiplexed Nanostring technology to monitor relative abundances of P. aeruginosa transcripts across clinical isolates, in serial samples, and for the purposes of comparing microbial physiology in vitro and in vivo The expression of 75 transcripts encoded by genes implicated in CF lung disease was measured in a variety of P. aeruginosa strains as well as RNA serial sputum samples …