A5077691670- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Antibiotic Resistance in Bacteria
- Cancer therapeutics and mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Pneumonia and Respiratory Infections
- Cytomegalovirus and herpesvirus research
- PI3K/AKT/mTOR signaling in cancer
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Infectious Diseases and Tuberculosis
- Adipokines, Inflammation, and Metabolic Diseases
- Inflammasome and immune disorders
- Dietary Effects on Health
- Liver Diseases and Immunity
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cell Adhesion Molecules Research
- Hydrogen's biological and therapeutic effects
- Sphingolipid Metabolism and Signaling
- Inflammatory Biomarkers in Disease Prognosis
- Virus-based gene therapy research
- Vitamin D Research Studies
- NF-κB Signaling Pathways
- Prostate Cancer Treatment and Research
- Hepatitis B Virus Studies
Vanderbilt University Medical Center
2006-2025
Vanderbilt University
2005-2023
University of Louisville
2012
Office of Infectious Diseases
2009
Johns Hopkins University
2008
Rationale: Fluoroquinolones are the most commonly prescribed antibiotic class in United States. They have potential to become first-line antituberculosis therapy, but effect of fluoroquinolone use on resistance Mycobacterium tuberculosis is not well characterized.Objectives: To determine prevalence and risk factors for fluoroquinolone-resistant a large States population.Methods: We identified all people with culture-confirmed enrolled TennCare (Medicaid) reported Tennessee Department Health...
ABSTRACT Heteroresistance is the coexistence of populations with differing nucleotides at a drug resistance locus within sample organisms. Although Sanger sequencing gold standard for sequencing, it may be less sensitive than deep detecting fluoroquinolone heteroresistance in Mycobacterium tuberculosis . Twenty-seven monoresistant and 11 fluoroquinolone-susceptible M. isolates were analyzed by Illumina sequencing. Individual reads to detect gyrA gyrB genes. fluoroquinolones was identified...
Fluoroquinolone resistance in Mycobacterium tuberculosis can be conferred by mutations gyrA or gyrB. The prevalence of outside the quinolone resistance-determining region (QRDR) gyrB is unclear, since such regions are rarely sequenced. M. isolates from 1,111 patients with newly diagnosed culture-confirmed Tennessee 2002 to 2009 were screened for phenotypic ofloxacin (>2 μg/ml). For each resistant isolate, two ofloxacin-susceptible selected: one antecedent fluoroquinolone exposure and...
Perinatal infection with Streptococcus agalactiae, or Group B (GBS), is associated preterm birth, neonatal sepsis, and stillbirth. Here, we study the interactions of GBS macrophages, essential sentinel immune cells that defend gravid reproductive tract. Transcriptional analyses GBS-macrophage co-cultures reveal enhanced expression a gene encoding putative metal resistance determinant, cadD. Deletion cadD reduces survival in efflux, to toxicity. In mouse model ascending during pregnancy,...
The aim of this study was to assess the sensitivity, specificity and time results mycobacterial growth indicator tube (MGIT) 960, microscopic observation drug susceptibility (MODS) assay nitrate reductase (NRA) compared with gold standard agar proportion method (PM), determine whether there is cross-resistance between older-generation fluoroquinolones moxifloxacin. Mycobacterium tuberculosis isolates from culture-confirmed patients 2002 2007 were tested for ofloxacin (2 mg/L) resistance by...
Significance Production of IL-1β is an essential component the inflammatory response and host defense. secretion dependent on activation intracellular platform termed inflammasome. The initial signals that drive inflammasome remains elusive. Here, we show bioactive lipid leukotriene B 4 enhances both transcriptional posttranscriptional programs activate in vivo vitro. We identified critical signaling required for assembly, secretion, its consequences skin Our data also suggest prevention LTB...
Abstract Phagocytosis requires the coordination of various classes receptors and activation multiple signaling programs, culminating in actin cytoskeletal rearrangement ingestion. Given pleiotropic nature events necessary for proper microbial ingestion, identifying molecules that control distinct steps phagocytosis could reveal potential strategies to enhance clearance. PTEN is a lipid/protein phosphatase traditionally recognized as tumor suppressor. While inhibits arms innate immune...
Myeloid cells are critical for systemic inflammation, microbial control, and organ damage during sepsis. MicroRNAs small noncoding RNAs that can dictate the outcome of The role myeloid-based expression microRNA-21 (miR-21) in sepsis is inconclusive. In this study, we show enhanced miR-21 both peritoneal macrophages neutrophils from septic C57BL/6J mice, deletion locus myeloid (miR-21Δmyel mice) animal survival, decreased bacterial growth, damage. Resistance to was associated with a reduction...
The skin innate immune response to methicillin-resistant Staphylococcus aureus (MRSA) culminates in the formation of an abscess prevent bacterial spread and tissue damage. Pathogen recognition receptors (PRRs) dictate balance between microbial control injury. Therefore, intracellular brakes are fundamental importance tune appropriate host defense while inducing resolution. inhibitor suppressor cytokine signaling 1 (SOCS-1), a known JAK/STAT inhibitor, prevents expression actions PRR adaptors...
Independent of HIV infection, extrapulmonary TB (EPTB) risk is increased in women, persons black race or foreign birth, and by genetic variants vitamin D receptor (VDR), interleukin-1 beta (IL-1β), toll-like (TLR)-2; functional correlates are unclear. We evaluated macrophage expression VDR, TLR2, cathelicidin, TNF-α, production IL-1β HIV-seronegative with previous EPTB, pulmonary TB, latent M. tuberculosis uninfected contacts. Persons pleural were excluded due to enhanced immune responses at...
Fluoroquinolone (FQ) exposure before tuberculosis (TB) diagnosis is common, but its effect on outcomes, including mortality, unclear.Among TB patients reported to the Tennessee Department of Health from 2007 2009, we assessed FQ within 6 months diagnosis. The primary outcome was combined endpoint death at time and during anti-tuberculosis treatment.Among 609 cases, 214 (35%) received FQs A total 71 (12%) persons died; 10 (2%) were dead 61 (10%) died treatment. In multivariable logistic...
ABSTRACT We report here on the development and validation of a prototype Invader Plus method for qualitative detection herpes simplex virus types 1 2 in cerebrospinal fluid (CSF). The combines PCR techniques single, closed-tube, continuous-reaction format that gives an analytical sensitivity approximately 10 copies per reaction. clinical specificity were 100.0% 98.6%, respectively, when results validated against obtained with colorimetric microtiter plate system by use CSF specimens.
Fluoroquinolone resistance in Mycobacterium tuberculosis is often conferred by DNA gyrase mutations. However, a substantial proportion of fluoroquinolone-resistant M. isolates do not have such Ofloxacin-resistant and lineage-matched ofloxacin-susceptible underwent WGS. Novel candidate mutations were confirmed Sanger sequencing conferral was assessed via site-directed mutagenesis allelic exchange. Ofloxacin MIC determined resazurin microtitre assay (REMA) the effects on MICs efflux pump...
Abstract Background Fluoroquinolone resistance in Mycobacterium tuberculosis (Mtb) is conferred by DNA gyrase mutations, but not all fluoroquinolone-resistant Mtb isolates have mutations detected. The optimal allele frequency threshold to identify resistance-conferring whole-genome sequencing unknown. Methods Phenotypically ofloxacin-resistant and lineage-matched ofloxacin-susceptible underwent at an average coverage depth of 868 reads. Polymorphisms within the...
Abstract Background We evaluated the relationship between response to efflux pump inhibition in fluoroquinolone-resistant Mycobacterium tuberculosis (Mtb) isolates and differences gene expression quantitative trait loci (eQTL). Methods determined ofloxacin minimum inhibitory concentration (MIC) for ofloxacin-resistant -susceptible Mtb without with inhibitor verapamil. performed RNA sequencing (RNA-seq), whole genome (WGS), eQTL analysis, focusing on pump, transport, secretion-associated...
Extrapulmonary TB (EPTB) occurs with increased frequency in persons underlying immunodeficiency. Even after recovery from acute illness, differences immune phenotype and activation persist. Studies defining characteristics of responses extrapulmonary may provide insights into factors that increase risk. We performed two case-control studies (in the United States Brazil) among HIV-seronegative adults previous EPTB (n = 9; 25), pulmonary 7; latent M. tuberculosis (Mtb) infection 11; uninfected...
Abstract Objective To determine at two distinct time points the prevalence of resistance to ofloxacin (OFX), representative class drug fluoroquinolones (FQs), in M. tuberculosis isolates susceptible first-line drugs. Results There were 279 from cohorts (2004–2005: 238 isolates; 2017: 41 isolates) that underwent OFX drug-susceptibility testing (critical concentration: 2 µg/ml). Of Cohort 1, no was detected (95% CI 0–0.016); likewise, 2, 0–0.086). Our findings suggest FQ use remains a viable...