Medicine and Health Sciences Commons^™

Uncharacterized And Lineage-Specific Accessory Genes Within The Proteus Mirabilis Pan-Genome Landscape, Robert F Potter, Kailun Zhang, Ben Reimler, Jamie Marino, Carol E Muenks, Kelly Alvarado, Meghan A Wallace, Lars F Westblade, Erin Mcelvania, Melanie L Yarbrough, David A Hunstad, Gautam Dantas, Carey-Ann D Burnham

2020-Current year OA Pubs

No abstract provided.

Pan-Cancer Analysis Of Post-Translational Modifications Reveals Shared Patterns Of Protein Regulation, Yifat Geffen, Yizhe Song, Akshay Govindan, Yize Li, Liang-Bo Wang, Li Ding, Et Al.

2020-Current year OA Pubs

Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology in both normal and cancer cells. Advances in mass spectrometry enable high-throughput, accurate, and sensitive measurement of PTM levels to better understand their role, prevalence, and crosstalk. Here, we analyze the largest collection of proteogenomics data from 1,110 patients with PTM profiles across 11 cancer types (10 from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns of changes in protein acetylation and phosphorylation involved in hallmark cancer processes. These patterns revealed subsets of tumors, from different cancer types, including those with …

Pan-Cancer Proteogenomics Connects Oncogenic Drivers To Functional States, Yize Li, Song Cao, Matthew A Wyczalkowski, Yizhe Song, Erik P Storrs, Michael C Wendl, Wen-Wei Liang, Nadezhda V Terekhanova, Fernanda Martins Rodrigues, Daniel Cui Zhou, Liang-Bo Wang, Jessika Baral, Milan G Chheda, Li Ding, Et Al.

2020-Current year OA Pubs

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of …

Ergosterol Distribution Controls Surface Structure Formation And Fungal Pathogenicity, Hau Lam Choy, Elizabeth A. Gaylord, Tamara L. Doering

2020-Current year OA Pubs

Ergosterol, the major sterol in fungal membranes, is critical for defining membrane fluidity and regulating cellular processes. Although ergosterol synthesis has been well defined in model yeast, little is known about sterol organization in the context of fungal pathogenesis. We identified a retrograde sterol transporter, Ysp2, in the opportunistic fungal pathogen

Bcl6, Irf2, And Notch2 Promote Nonclassical Monocyte Development, Kevin W O'Connor, Tiantian Liu, Sunkyung Kim, Carlos G Briseño, Katia Georgopoulos, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

Ly6C

Entry Receptor Ldlrad3 Is Required For Venezuelan Equine Encephalitis Virus Peripheral Infection And Neurotropism Leading To Pathogenesis In Mice, Natasha M Kafai, Hana Janova, Matthew D Cain, Yael Alippe, Stefanie Muraro, Alan Sariol, Michelle Elam-Noll, Robyn S Klein, Michael S Diamond

2020-Current year OA Pubs

Venezuelan equine encephalitis virus (VEEV) is an encephalitic alphavirus responsible for epidemics of neurological disease across the Americas. Low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3) is a recently reported entry receptor for VEEV. Here, using wild-type and Ldlrad3-deficient mice, we define a critical role for LDLRAD3 in controlling steps in VEEV infection, pathogenesis, and neurotropism. Our analysis shows that LDLRAD3 is required for efficient VEEV infection and pathogenesis prior to and after central nervous system invasion. Ldlrad3-deficient mice survive intranasal and intracranial VEEV inoculation and show reduced infection of neurons in different brain regions. As LDLRAD3 is a determinant …

S100a8 And S100a9 In Hematologic Malignancies: From Development To Therapy, Farnaz Razmkhah, Sena Kim, Sora Lim, Abdul-Jalil Dania, Jaebok Choi

2020-Current year OA Pubs

S100A8 and S100A9 are multifunctional proteins that can initiate various signaling pathways and modulate cell function both inside and outside immune cells, depending on their receptors, mediators, and molecular environment. They have been reported as dysregulated genes and proteins in a wide range of cancers, including hematologic malignancies, from diagnosis to response to therapy. The role of S100A8 and S100A9 in hematologic malignancies is highlighted due to their ability to work together or as antagonists to modify cell phenotype, including viability, differentiation, chemosensitivity, trafficking, and transcription strategies, which can lead to an oncogenic phase or reduced symptoms. In this review …

Participatory Logic Modeling In A Multi-Site Initiative To Advance Implementation Science, Douglas V Easterling, Rebekah R Jacob, Ross C Brownson, Debra Haire-Joshu, Daniel A Gundersen, Heather Angier, Jennifer E Devoe, Sonja Likumahuwa-Ackman, Thuy Vu, Russell E Glasgow, Robert Schnoll

2020-Current year OA Pubs

BACKGROUND: Logic models map the short-term and long-term outcomes that are expected to occur with a program, and thus are an essential tool for evaluation. Funding agencies, especially in the United States (US), have encouraged the use of logic models among their grantees. They also use logic models to clarify expectations for their own funding initiatives. It is increasingly recognized that logic models should be developed through a participatory approach which allows input from those who carry out the program being evaluated. While there are many positive examples of participatory logic modeling, funders have generally not engaged grantees in developing …

Perspectives On Long-Acting Formulations Of Pre-Exposure Prophylaxis (Prep) Among Men Who Have Sex With Men Who Are Non-Adherent To Daily Oral Prep In The United States, Brooke G Rogers, R R Patel, K Curoe, J Villalobos, A Underwood, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP.

METHODS: We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants' perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis.

RESULTS: Participants …

Microglial Rev-Erbα Regulates Inflammation And Lipid Droplet Formation To Drive Tauopathy In Male Mice, Jiyeon Lee, Julie M Dimitry, Jong Hee Song, Minsoo Son, Patrick W Sheehan, Melvin W King, G Travis Tabor, Young Ah Goo, Mitchell A Lazar, Leonard Petrucelli, Erik S Musiek

2020-Current year OA Pubs

Alzheimer's disease, the most common age-related neurodegenerative disease, is characterized by tau aggregation and associated with disrupted circadian rhythms and dampened clock gene expression. REV-ERBα is a core circadian clock protein which also serves as a nuclear receptor and transcriptional repressor involved in lipid metabolism and macrophage function. Global REV-ERBα deletion has been shown to promote microglial activation and mitigate amyloid plaque formation. However, the cell-autonomous effects of microglial REV-ERBα in healthy brain and in tauopathy are unexplored. Here, we show that microglial REV-ERBα deletion enhances inflammatory signaling, disrupts lipid metabolism, and causes lipid droplet (LD) accumulation specifically in male …

Rapid Direct Detection Of Sars-Cov-2 Aerosols In Exhaled Breath At The Point Of Care, Dishit P Ghumra, Nishit Shetty, Kevin R Mcbrearty, Joseph V Puthussery, Benjamin J Sumlin, Woodrow D Gardiner, Brookelyn M Doherty, Jordan P Magrecki, Jane A O'Halloran, Rachel M Presti, Traci L Bricker, Adrianus C M Boon, Carla M Yuede, John R Cirrito, Rajan K Chakrabarty, Et Al.

2020-Current year OA Pubs

Airborne transmission via virus-laden aerosols is a dominant route for the transmission of respiratory diseases, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Direct, non-invasive screening of respiratory virus aerosols in patients has been a long-standing technical challenge. Here, we introduce a point-of-care testing platform that directly detects SARS-CoV-2 aerosols in as little as two exhaled breaths of patients and provides results in under 60 s. It integrates a hand-held breath aerosol collector and a llama-derived, SARS-CoV-2 spike-protein specific nanobody bound to an ultrasensitive micro-immunoelectrode biosensor, which detects the oxidation of tyrosine amino acids present in SARS-CoV-2 viral particles. Laboratory …

Sustainable Development For Mobile Health Apps Using The Human-Centered Design Process, Qingfan An, Marjorie M Kelley, Audra Hanners, Po-Yin Yen

2020-Current year OA Pubs

Well-documented scientific evidence indicates that mobile health (mHealth) apps can improve the quality of life, relieve symptoms, and restore health for patients. In addition to improving patients' health outcomes, mHealth apps reduce health care use and the cost burdens associated with disease management. Currently, patients and health care providers have a wide variety of choices among commercially available mHealth apps. However, due to the high resource costs and low user adoption of mHealth apps, the cost-benefit relationship remains controversial. When compared to traditional expert-driven approaches, applying human-centered design (HCD) may result in more useable, acceptable, and effective mHealth apps. In …

Genetic Modifiers Of Mendelian Monogenic Collagen Iv Nephropathies In Humans And Mice, Constantinos Deltas, Gregory Papagregoriou, Stavroula F Louka, Apostolos Malatras, Frances Flinter, Daniel P Gale, Susie Gear, Oliver Gross, Julia Hoefele, Rachel Lennon, Jeffrey H Miner, Alessandra Renieri, Judy Savige, A Neil Turner

2020-Current year OA Pubs

Familial hematuria is a clinical sign of a genetically heterogeneous group of conditions, accompanied by broad inter- and intrafamilial variable expressivity. The most frequent condition is caused by pathogenic (or likely pathogenic) variants in the collagen-IV genes,

Design, Synthesis, And Evaluation Of Novel Δ2‑Thiazolino2‑Pyridone Derivatives That Potentiate Isoniazid Activity In An Isoniazid-Resistant Mycobacterium Tuberculosis Mutant, Souvik Sarkar, Anne E. Mayer Bridwell, Erin R. Wang, Samuel R. Mckee, Joy Valenta, Gregory A. Harrison, Kelly N. Flentie, Frederick L. Henry, Christina L. Stallings, Et Al.

2020-Current year OA Pubs

No abstract provided.

New Concepts In Steroid Glaucoma, A M. Levin, E G. Sieck

2020-Current year OA Pubs

No abstract provided.

Interpreting The Mechanism Of Synergism For Drug Combinations Using Attention-Based Hierarchical Graph Pooling, Zehao Dong, Heming Zhang, Yixin Chen, Philip R O Payne, Fuhai Li

2020-Current year OA Pubs

Synergistic drug combinations provide huge potentials to enhance therapeutic efficacy and to reduce adverse reactions. However, effective and synergistic drug combination prediction remains an open question because of the unknown causal disease signaling pathways. Though various deep learning (AI) models have been proposed to quantitatively predict the synergism of drug combinations, the major limitation of existing deep learning methods is that they are inherently not interpretable, which makes the conclusions of AI models untransparent to human experts, henceforth limiting the robustness of the model conclusion and the implementation ability of these models in real-world human-AI healthcare. In this paper, we …

Changing Severity And Epidemiology Of Adults Hospitalized With Coronavirus Disease 2019 (Covid-19) In The United States After Introduction Of Covid-19 Vaccines, March 2021-August 2022, Noah Kojima, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies.

METHODS: Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed.

RESULTS: Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), …

The Proteome Of Extracellular Vesicles Of The Lung Fluke Paragonimus Kellicotti Produced In Vitro And In The Lung Cyst, Lucia S Di Maggio, Kerstin Fischer, Devyn Yates, Kurt C Curtis, Bruce A Rosa, John Martin, Petra Erdmann-Gilmore, Robert S W Sprung, Makedonka Mitreva, R Reid Townsend, Gary J Weil, Peter U Fischer

2020-Current year OA Pubs

Paragonimiasis is a zoonotic, food-borne trematode infection that affects 21 million people globally. Trematodes interact with their hosts via extracellular vesicles (EV) that carry protein and RNA cargo. We analyzed EV in excretory-secretory products (ESP) released by Paragonimus kellicotti adult worms cultured in vitro (EV ESP) and EV isolated from lung cyst fluid (EV CFP) recovered from infected gerbils. The majority of EV were approximately 30-50 nm in diameter. We identified 548 P. kellicotti-derived proteins in EV ESP by mass spectrometry and 8 proteins in EV CFP of which 7 were also present in EV ESP. No parasite-derived proteins were …

Efficacy Of Checkpoint Inhibition After Car-T Failure In Aggressive B-Cell Lymphomas: Outcomes From 15 Us Institutions, Ajay Major, Michael J Slade, Nathan Singh, Et Al.

2020-Current year OA Pubs

Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate …

Genomic Landscape Of Tp53-Mutated Myeloid Malignancies, Haley J Abel, Karolyn A Oetjen, Christopher A Miller, Sai M Ramakrishnan, Ryan B Day, Nichole M Helton, Catrina C Fronick, Robert S Fulton, Sharon E Heath, Stefan P Tarnawsky, Sridhar Nonavinkere Srivatsan, Eric J Duncavage, Molly C Schroeder, Jacqueline E Payton, David H Spencer, Matthew J Walter, Peter Westervelt, John F Dipersio, Timothy J Ley, Daniel C Link

2020-Current year OA Pubs

TP53-mutated myeloid malignancies are associated with complex cytogenetics and extensive structural variants, which complicates detailed genomic analysis by conventional clinical techniques. We performed whole-genome sequencing (WGS) of 42 acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS) cases with paired normal tissue to better characterize the genomic landscape of TP53-mutated AML/MDS. WGS accurately determines TP53 allele status, a key prognostic factor, resulting in the reclassification of 12% of cases from monoallelic to multihit. Although aneuploidy and chromothripsis are shared with most TP53-mutated cancers, the specific chromosome abnormalities are distinct to each cancer type, suggesting a dependence on the tissue of origin. ETV6 expression …

Risk Of Autism Spectrum Disorder And Association Of Its Symptoms With Psychiatric And Substance Use Disorders In Non-Clinical Student Sample In Kenya: Cross-Sectional Study, Victoria N Mutiso, David M Ndetei, Esther N Muia, Monicah Masake, Rita K Alietsi, Lydia Onsinyo, Christine Musyimi, Daniel Mamah

2020-Current year OA Pubs

BACKGROUND: The prevalence and patterns of autism spectrum disorder (ASD) symptoms/traits and the associations of ASD with psychiatric and substance use disorders has not been documented in non-clinical students in Sub-Saharan Africa, and Kenya in particular.

AIMS: To document the risk level of ASD and its traits in a Kenyan student population (high school, college and university) using the Autism-Spectrum Quotient (AQ); and to determine the associations between ASD and other psychiatric and substance use disorders.

METHOD: This was a cross-sectional study among students (

RESULTS: Of the total sample, 54 (0.56%) were at high risk of ASD. Sociodemographic differences …

Prevalence And Trends Of Advanced Hiv Disease Among Antiretroviral Therapy-Naïve And Antiretroviral Therapy-Experienced Patients In South Africa Between 2010-2021: A Systematic Review And Meta-Analysis, Marcel K Kitenge, Geoffrey Fatti, Ingrid Eshun-Wilson, Omololu Aluko, Peter Nyasulu

2020-Current year OA Pubs

BACKGROUND: Despite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with Advanced HIV Disease (AHD). We aimed to estimate the prevalence of AHD among ART-naive and ART-experienced patients in South Africa using studies published between January 2010 and May 2022.

METHODS: We searched for relevant data on PubMed, CINAHL, Scopus and other sources, with a geographical filters limited to South Africa, up to May 31, 2022. Two reviewers conducted all screening, eligibility assessment, data extraction, and critical appraisal. We synthesized the data using the …

Transcranial Focused Ultrasound-Induced Blood‒Brain Barrier Opening In Mice Without Shaving Hairs, Lu Xu, Yan Gong, Chih-Yen Chien, Eric Leuthardt, Hong Chen

2020-Current year OA Pubs

Acoustic coupling through hairs remains a challenge to performing transcranial-focused ultrasound procedures. Here, we demonstrated that this challenge could be addressed by using oil as the coupling medium, leveraging oil's high affinity to hairs due to their inherent hydrophobicity. We compared focused ultrasound-induced blood-brain barrier opening (FUS-BBBO) outcomes in mice under three coupling conditions: oil with hairs ("oil + hairs"), ultrasound gel with hair shaving ("ultrasound gel + no hair"), and ultrasound gel with hairs ("ultrasound gel + hairs"). The quality of the coupling was evaluated by [Formula: see text]-weighted magnetic resonance imaging (MRI) and passive cavitation detection (PCD). The …

Chromophore Carbonyl Twisting In Fluorescent Biosensors Encodes Direct Readout Of Protein Conformations With Multicolor Switching, Malin J Allert, Shivesh Kumar, You Wang, Lorena S Beese, Homme W Hellinga

2020-Current year OA Pubs

Fluorescent labeling of proteins is a powerful tool for probing structure-function relationships with many biosensing applications. Structure-based rules for systematically designing fluorescent biosensors require understanding ligand-mediated fluorescent response mechanisms which can be challenging to establish. We installed thiol-reactive derivatives of the naphthalene-based fluorophore Prodan into bacterial periplasmic glucose-binding proteins. Glucose binding elicited paired color exchanges in the excited and ground states of these conjugates. X-ray structures and mutagenesis studies established that glucose-mediated color switching arises from steric interactions that couple protein conformational changes to twisting of the Prodan carbonyl relative to its naphthalene plane. Mutations of residues contacting the carbonyl …

Differential Processing Of Risk And Reward In Delinquent And Non-Delinquent Youth, Natasha Duell, Michael T Perino, Ethan M Mccormick, Eva H Telzer

2020-Current year OA Pubs

The present study examined the behavioral and neural differences in risky decision-making between delinquent (n = 23) and non-delinquent (n = 27) youth ages 13-17 years (M = 16, SD = 0.97) in relation to reward processing. While undergoing functional neuroimaging, participants completed an experimental risk task wherein they received feedback about the riskiness of their behavior in the form of facial expressions that morphed from happy to angry. Behavioral results indicated that delinquent youth took fewer risks and earned fewer rewards on the task than non-delinquent youth. Results from whole-brain analyses indicated no group differences in sensitivity to punishments …

Vegf-B Prevents Excessive Angiogenesis By Inhibiting Fgf2/Fgfr1 Pathway, Chunsik Lee, David M Ornitz, Et Al.

2020-Current year OA Pubs

Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting …

Phase Iii Pivotal Comparative Clinical Trial Of Intranasal (Incovacc) And Intramuscular Covid 19 Vaccine (Covaxin®), Chandramani Singh, Michael S Diamond, David T Curiel, Et Al.

2020-Current year OA Pubs

One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin

A Survey Of Surgical Patients' Perspectives And Preferences Towards General Anesthesia Techniques And Shared-Decision Making, Bethany R Tellor Pennington, Mary C Politi, Arbi Ben Abdallah, Allison M Janda, Ingrid Eshun-Wilsonova, Nastassjia G Debourbon, Lilly Siderowf, Heidi Klosterman, Sachin Kheterpal, Michael S Avidan

2020-Current year OA Pubs

BACKGROUND: The decision about which type of general anesthetic to administer is typically made by the clinical team without patient engagement. This study examined patients' preferences, experiences, attitudes, beliefs, perceptions, and perceived social norms about anesthesia and about engaging in the decision regarding general anesthetic choice with their clinician.

METHODS: We conducted a survey in the United States, sent to a panel of surgical patients through Qualtrics (Qualtrics, Provo, UT) from March 2022 through May 2022. Questions were developed based on the Theory of Planned Behavior and validated measures were used when available. A patient partner who had experienced both …

Sickle Cell Disease Treatment With Arginine Therapy (Start): Study Protocol For A Phase 3 Randomized Controlled Trial, Chris A Rees, Fahd Ahmad, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.

METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 …

Defining The Roles Of Pyruvate Oxidation, Tca Cycle, And Mannitol Metabolism In Methicillin-Resistant Staphylococcus Aureus Catheter-Associated Urinary Tract Infection, Santosh Paudel, Sarah Guedry, Chloe L P Obernuefemann, Scott J. Hultgren, Jennifer N. Walker, Ritwij Kulkarni

2020-Current year OA Pubs

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of complicated urinary tract infection (UTI) associated with the use of indwelling urinary catheters. Previous reports have revealed host and pathogen effectors critical for MRSA uropathogenesis. Here, we sought to determine the significance of specific metabolic pathways during MRSA UTI. First, we identified four mutants from the Nebraska transposon mutant library in the MRSA JE2 background that grew normally in rich medium but displayed significantly reduced growth in pooled human urine (HU). This prompted us to transduce the uropathogenic MRSA 1369 strain with the transposon mutants in