Medical Microbiology Commons^™

Rnai-Mediated Gene Knockdown By Microinjection In The Model Entomopathogenic Nematode Heterorhabditis Bacteriophora., Ramesh Ratnappan, Jonathan Vadnal, Melissa Keaney, Ioannis Eleftherianos, Damien O'Halloran, John M. Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Parasitic nematodes threaten the health of humans and livestock and cause a major financial and socioeconomic burden to modern society. Given the widespread distribution of diseases caused by parasitic nematodes there is an urgent need to develop tools that will elucidate the genetic complexity of host-parasite interactions. Heterorhabditis bacteriophora is a parasitic nematode that allows simultaneous monitoring of nematode infection processes and host immune function, and offers potential as a tractable model for parasitic nematode infections. However, molecular tools to investigate these processes are required prior to its widespread acceptance as a robust model organism. In this paper we …

Cold Atmospheric Plasma Inhibits Hiv-1 Replication In Macrophages By Targeting Both The Virus And The Cells., Olga Volotskova, Larisa Dubrovsky, Michael Keidar, Michael Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Cold atmospheric plasma (CAP) is a specific type of partially ionized gas that is less than 104°F at the point of application. It was recently shown that CAP can be used for decontamination and sterilization, as well as anti-cancer treatment. Here, we investigated the effects of CAP on HIV-1 replication in monocyte-derived macrophages (MDM). We demonstrate that pre-treatment of MDM with CAP reduced levels of CD4 and CCR5, inhibiting virus-cell fusion, viral reverse transcription and integration. In addition, CAP pre-treatment affected cellular factors required for post-entry events, as replication of VSV-G-pseudotyped HIV-1, which by-passes HIV receptor-mediated fusion at the plasma …

Coordination Of Rna Polymerase Ii Pausing And 3' End Processing Factor Recruitment With Alternative Polyadenylation, Becky Fusby, Soojin Kim, Benjamin Erickson, Hyunmin Kim, Martha L. Peterson, David L Bentley

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Most mammalian genes produce transcripts whose 3' ends are processed at multiple alternative positions by cleavage/polyadenylation (CPA). Poly(A) site cleavage frequently occurs cotranscriptionally and is facilitated by CPA factor binding to the RNA polymerase II (Pol II) C-terminal domain (CTD) phosphorylated on Ser2 residues of its heptad repeats (YS₂PTSPS). The function of cotranscriptional events in the selection of alternative poly(A) sites is poorly understood. We investigated Pol II pausing, CTD Ser2 phosphorylation, and processing factor CstF recruitment at wild-type and mutant IgM transgenes that use alternative poly(A) sites to produce mRNAs encoding the secreted and membrane-bound forms of …

Antibiotic Efficacy And Interaction In Escherichia Coli During Varying Nutrient Conditions, Kristina K. Millar

Scripps Senior Theses

Due to the recent rise in antibiotic resistant pathogens, and the difficulties surrounding the quest for new antibiotics, many researchers have started revisiting antibiotic interactions in hopes of finding new treatment options. The primary outcome of this project was to examine the efficacy of concomitant antibiotic use under varying nutrient conditions, to identify variations in antibiotic interactions. Antibiotic interactions were studied, utilizing E. coli as a model bacterial system, grown in four different media types. E. coli cultures were treated with streptomycin, tobramycin, erythromycin, and amikacin individually and in a pairwise fashion at varying doses. We found that at least …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Viability Of Developmental Stages Of Schistosoma Mansoni Quantified With Xcelligence Worm Real-Time Motility Assay (Xworm)., Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Jeff T. Irelan, Michael J. Smout

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with helminth parasites causes morbidity and mortality in billions of people and livestock worldwide. Where anthelmintic drugs are available, drug resistance is a major problem in livestock parasites, and a looming threat to public health. Monitoring the efficacy of these medicines and screening for new drugs has been hindered by the lack of objective, high-throughput approaches. Several cell monitoring technologies have been adapted for parasitic worms, including video-, fluorescence-, metabolism enzyme- and impedance-based tools that minimize the screening bottleneck. Using the xCELLigence impedance-based system we previously developed a motility-viability assay that is applicable for a range of helminth parasites. …

Role Of B Cell Receptor Signaling In Il-10 Production By Normal And Malignant B-1 Cells., Sara S Alhakeem, Vishal J Sindhava, Mary K Mckenna, Beth W Gachuki, John C Byrd, Natarajan Muthusamy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells are considered innate immune cells, which produce the majority of natural antibodies. B-1 cell responses to B cell receptor (BCR) and Toll-like receptor ligation are tightly regulated owing to the cross-reactivity to self-antigens. CD5 has been shown to play a major role in downregulation of BCR responses in B-1 cells. Here, we provide evidence for another mechanism by which BCR response is regulated in B-1 cells. B-1 cells, as well as their malignant counterpart, B cell chronic lymphocytic leukemia (B-CLL) cells, produce interleukin-10 (IL-10) constitutively. IL-10 secretion by normal B-1 cells downregulates their proliferation responses to BCR ligation. …

Post Operative Fungal Endopthalmitis Due To Geotrichum Candidum, Thein Myint, Matthew J. Dykhuizen, Carolyn H. Mcdonald, Julie A. Ribes

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Geotrichum species have been rarely reported as the cause of sepsis, disseminated infection in immunosuppressed patients. The patient we describe developed indolent endophthalmitis four months after her routine right eye cataract surgery. The intraoperative sample from right vitreous fluid grew Geotrichum candidum. The patient underwent vitrectomy, artificial lens explantation and intravitreal injection of amphotericin B followed by oral voriconazole. Despite these interventions, she underwent enucleation. This is the first published case of Geotrichum candidum endophthalmitis.

Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes To Adopt A Tumorigenic Phenotype, Sujittra Chaidayet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm Jones, Paul J. Brindley, Jeffrey M. Bethony, +9 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Throughout Asia there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes including chronic inflammation and secretion of parasite proteins into the biliary epithelium drive infection towards cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown.

Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterised the EV proteome and associated changes in cholangiocytes after EV uptake, and detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and …

Tuberculosis And Cardiovascular Disease: Linking The Epidemics, Moises A. Huaman, David Henson, Eduardo Ticona, Timothy R. Sterling, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, …

A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe

Department of Biological Sciences Publications

The physical characteristics of bacteriophages establish them as viable candidates for downstream development of pathogen detection assays and biocontrol measures. To utilize phages for such purposes, a detailed knowledge of their host interaction mechanisms is a prerequisite. There is currently a wealth of knowledge available concerning Gram-negative phage-host interaction, but little by comparison for Gram-positive phages and Listeria phages in particular. In this research, the lytic spectrum of two recently isolated Listeria monocytogenes phages (vB_LmoS_188 and vB_LmoS_293) was determined, and the genomic basis for their observed serotype 4b/4e host-specificity was investigated using comparative genomics. The late tail genes of these …

Advances In The Diagnosis Of Human Opisthorchiasis: Development Of Opisthorchis Viverrini Antigen Detection In Urine, Chanika Worasith, Christine Kamamia, Anna Yakovleva, Kunyarat Duenngai, Chompunoot Wangboon, Jeffrey M. Bethony, +8 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated "heavy" infections in single villages to widespread "light" OV infections distributed over wide geographical areas. Currently, the "gold standard" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV …

Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated …

Borrelia Burgdorferi Reva Significantly Affects Pathogenicity And Host Response In The Mouse Model Of Lyme Disease, Rebecca Byram, Robert A. Gaultney, Angela M. Floden, Christopher Hellekson, Brandee L. Stone, Amy Bowman, Brian Stevenson, Barbara J. B. Johnson, Catherine A. Brissette

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, expresses RevA and numerous outer surface lipoproteins during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA is poised to interact with the extracellular matrix of the host. To further define the role(s) of RevA during mammalian infection, we created a mutant that is unable to produce RevA. The mutant was still infectious to mice, although it was significantly less well able to infect cardiac tissues. Complementation of the mutant with a wild-type revA gene restored heart infectivity to wild-type levels. Additionally, revA mutants led to increased evidence of arthritis, …

Role Of The Dna Sensor Sting In Protection From Lethal Infection Following Corneal And Intracerebral Challenge With Herpes Simplex Virus 1, Zachary M. Parker, Aisling A. Murphy, David. A. Leib

Dartmouth Scholarship

STING is a protein in the cytosolic DNA and cyclic dinucleotide sensor pathway that is critical for the initiation of innate responses to infection by various pathogens. Consistent with this, herpes simplex virus 1 (HSV-1) causes invariable and rapid lethality in STING-deficient (STING(-/-)) mice following intravenous (i.v.) infection. In this study, using real-time bioluminescence imaging and virological assays, as expected, we demonstrated that STING(-/-) mice support greater replication and spread in ocular tissues and the nervous system. In contrast, they did not succumb to challenge via the corneal route even with high titers of a virus that was routinely lethal …

Application Of Β-Lactamase Reporter Fusions As An Indicator Of Effector Protein Secretion During Infections With The Obligate Intracellular Pathogen Chlamydia Trachomatis , Konrad E. Mueller, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chlamydia spp. utilize multiple secretion systems, including the type III secretion system (T3SS), to deploy host-interactive effector proteins into infected host cells. Elucidation of secreted proteins has traditionally required ectopic expression in a surrogate T3SS followed by immunolocalization of endogenous candidate effectors to confirm secretion by chlamydiae. The ability to transform Chlamydia and achieve stable expression of recombinant gene products has enabled a more direct assessment of secretion. We adapted TEM-1 β-lactamase as a reporter system for assessment of chlamydial protein secretion. We provide evidence that this system facilitates visualization of secretion in the context of infection. Specifically, our findings …

The Right Tool For The Job: Detection Of Soil-Transmitted Helminths In Areas Co-Endemic For Other Helminths, Maria V. Periago, Renata C. Diniz, Simone A. Pinto, Anna Yakovleva, Rodrigo Correa-Oliveira, David J. Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Due to the recent increased use of the McMaster (MM) fecal egg counting method for assessing benzimidazole drug efficacy for treating soil-transmitted helminth (STH) infections, the aim of the current study was to determine the operational value of including the MM method alongside the Kato-Katz (KK) fecal thick smear to increase the diagnostic sensitivity when STHs are co-endemic with trematode helminths (e.g., Schistosoma mansoni).

Methods

A cross-sectional study was conducted in school-aged children aged 4-18 years in the northeastern region of the State of Minas Gerais (Brazil), where Necator americanus, Ascaris lumbricoides, Trichuris trichiura, and S …

Intracellular Listeria Monocytogenes Comprises A Minimal But Vital Fraction Of The Intestinal Burden Following Foodborne Infection, Grant S. Jones, Kate M. Bussell, Tanya Myers-Morales, Abigail M. Fieldhouse, Elsa N. Bou Ghanem, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is a highly adaptive bacterium that replicates as a free-living saprophyte in the environment as well as a facultative intracellular pathogen that causes invasive foodborne infections. The intracellular life cycle of L. monocytogenes is considered to be its primary virulence determinant during mammalian infection; however, the proportion of L. monocytogenes that is intracellular in vivo has not been studied extensively. In this report, we demonstrate that the majority of wild-type (strain EGDe) and mouse-adapted (InlA^m-expressing) L. monocytogenes recovered from the mesenteric lymph nodes (MLN) was extracellular within the first few days after foodborne infection. In addition, …

Correlation Of Periodontal Pathogens In Concurrent Endodontic-Periodontal Diseases, Amela Lačević, Federico Foschi, Lejla Pojskić, Naris Pojskić, Kasim Bajrović, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Objectives: This study investigated the correlation between Tannerella forsythia, Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans at dual sites in concurrent endodonticperiodontal diseases.

Material and methods: Samples were collected from endodontium and periodontium in cases of concurrent endodontic-periodontal diseases from thirty participants. The sensitivity and specificity of SYBR Green real-time PCR was used to identify the targeted species. Absolute number of targeted genome copies in tested samples were extrapolated from respective calibration curve.

Results: No statistical difference was found in the number of detected endodontic-periodontal pathogens between the endodontium and periodontium. The Pearson test …

Zbtb20 Is A Sequence-Specific Transcriptional Repressor Of Alpha-Fetoprotein Gene, Hai Zhang, Dongmei Cao, Luting Zhou, Ye Zhang, Xiaoqin Guo, Hui Li, Yuxia Chen, Brett T. Spear, Jia-Wei Wu, Zhifang Xie, Weiping J Zhang

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Alpha-fetoprotein (AFP) represents a classical model system to study developmental gene regulation in mammalian cells. We previously reported that liver ZBTB20 is developmentally regulated and plays a central role in AFP postnatal repression. Here we show that ZBTB20 is a sequence-specific transcriptional repressor of AFP. By ELISA-based DNA-protein binding assay and conventional gel shift assay, we successfully identified a ZBTB20-binding site at -104/-86 of mouse AFP gene, flanked by two HNF1 sites and two C/EBP sites in the proximal promoter. Importantly, mutation of the core sequence in this site fully abolished its binding to ZBTB20 in vitro, as well …

Selective Involvement Of The Checkpoint Regulator Vista In Suppression Of B-Cell, But Not T-Cell, Responsiveness By Monocytic Myeloid-Derived Suppressor Cells From Mice Infected With An Immunodeficiency-Causing Retrovirus, Kathy A. Green, Li Wang, Randolph J. Noelle, William R. Green

Dartmouth Scholarship

Inhibition of T-cell responses in tumor microenvironments by myeloid-derived suppressor cells (MDSCs) is widely accepted. We demonstrated augmentation of monocytic MDSCs whose suppression of not only T-cell, but also B-cell, responsiveness paralleled the immunodeficiency during LP-BM5 retrovirus infection. MDSCs inhibited T cells by inducible nitric oxide synthase (iNOS)/nitric oxide (NO), but uniquely, inhibition of B cells was ~50% dependent each on iNOS/NO and the MDSC-expressed negative-checkpoint regulator VISTA. Blockade with a combination of iNOS/NO and VISTA caused additive or synergistic abrogation of MDSC-mediated suppression of B-cell responsiveness.

Levels Of 8-Oxodg Predict Hepatobiliary Pathology In Opisthorchis Viverrini Endemic Settings In Thailand., Prasert Saichua, Anna Yakovleva, Christine Kamamia, Amar R. Jariwala, Paul J. Brindley, Jeffrey M. Bethony, + 8 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is distinct among helminth infections as it drives a chronic inflammatory response in the intrahepatic bile duct that progresses from advanced periductal fibrosis (APF) to cholangiocarcinoma (CCA). Extensive research shows that oxidative stress (OS) plays a critical role in the transition from chronic O. viverrini infection to CCA. OS also results in the excision of a modified DNA lesion (8-oxodG) into urine, the levels of which can be detected by immunoassay. Herein, we measured concentrations of urine 8-oxodG by immunoassay from the following four groups in the Khon Kaen Cancer Cohort study: (1) O. viverrini negative individuals, (2) …

Tonb Not Directly Related To Efflux Of Antibiotics In E. Coli, Amber Gombash

Honors Projects

Studies in Pseudomonas aeruginosa have suggested that the TonB energy transduction system directly contributes to efflux-mediated antibiotic resistance, ostensibly by energizing one or more efflux systems. We have found ∆tonB strains of Escherichia coli to similarly be more sensitive to certain antibiotics relative to wild-type strains. To test the hypothesis that this enhanced sensitivity involved the energization of efflux systems, sensitivity patterns for a variety of antibiotics were evaluated using a set of strains differentially lacking genes encoding the Acr efflux system, the universal outer membrane efflux portal TolC, and TonB. No correlation was evident between the resistance phenotypes of …

Identification Of Transcription Factors Gzf3, Rfx1, Orf19.3928 As Being Implicated In Candida-Bacterial Interactions., Joni Watson

Undergraduate Honors Theses

Candida albicans is an opportunistic pathogen that is present in the normal flora in a majority of individuals. One key factor in C. albicans virulence is the ability to change its morphology from yeast to an elongated or hyphal form. The regulation of this morphogenesis relies in part upon quorum sensing (QS) molecules. C. albicans often exists as part of a mixed culture alongside other microbes and is influenced by their presence as well as the presence of QS molecules that they produce. In this study, a library of diploid homozygous transcriptional regulator knockout (TRKO) mutants were screened to identify …

Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski

Honors Scholar Theses

Each year, nearly 800,000 individuals residing in the United States will have a stroke. Of these, about 130,000 cases will prove fatal while many of the survivors will be forced to live with disability for the remainder of their lives. Out of all strokes over 87% are ischemic strokes. The widespread incidence of this debilitating condition costs the United States an estimated $36.5 billion dollars every single year. Despite this, clinicians are armed with very little to combat the disease. Recent research developments have brought about the rise in awareness about the importance of the microbiome, the various gut flora …

A Microrna Profile Associated With Opisthorchis Viverrini-Induced Cholangiocarcinoma In Tissue And Plasma., Jordan Plieskatt, Gabriel Rinaldi, Yanjun Feng, Jin Peng, Samantha Easley, Xinying Jia, Jeremy Potriquet, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J Brindley, Jeffrey Bethony, Jason Mulvenna

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive tumor of the bile duct, and a significant public health problem in East Asia, where it is associated with infection by the parasiteOpisthorchis viverrini. ICC is often detected at an advanced stage and with a poor prognosis, making a biomarker for early detection a priority.

Methods

We have comprehensively profiled miRNA expression levels in ICC tumor tissue using small RNA-Seq and validated these profiles using quantitative PCR on matched plasma samples.

Results

Distinct miRNA profiles were associated with increasing histological differentiation of ICC tumor tissue. We also observed that histologically …

Opisthorchiasis: An Overlooked Danger, Ludmila M. Ogorodova, Olga S. Fedorova, Banchob Sripa, Viatcheslav A. Mordvinov, Aleksei V. Katokhin, Paul J. Brindley, The Topic Consortium

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Opisthorchiasis: An Overlooked Danger., Ludmila M Ogorodova, Olga S Fedorova, Banchob Sripa, Viatcheslav A Mordvinov, Aleksei V Katokhin, Jennifer Keiser, Peter Odermatt, Paul J. Brindley, Oleg A Mayboroda, Thirumalaisamy P Velavan, Maxim B Freidin, Alexey E Sazonov, Irina V Saltykova, Mariya Y Pakharukova, Yulia V Kovshirina, Kostas Kaloulis, Olga Y Krylova, Maria Yazdanbakhsh

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Apparent Role For Borrelia Burgdorferi Luxs During Mammalian Infection, William K. Arnold, Christina R. Savage, Alyssa D. Antonicello, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, controls protein expression patterns during its tick-mammal infection cycle. Earlier studies demonstrated that B. burgdorferi synthesizes 4,5-dihydroxy-2,3-pentanedione (autoinducer-2 [AI-2]) and responds to AI-2 by measurably changing production of several infection-associated proteins. luxS mutants, which are unable to produce AI-2, exhibit altered production of several proteins. B. burgdorferi cannot utilize the other product of LuxS, homocysteine, indicating that phenotypes of luxS mutants are not due to the absence of that molecule. Although a previous study found that a luxS mutant was capable of infecting mice, a critical caveat to those results is that bacterial …

Zhx2 Enhances The Cytotoxicity Of Chemotherapeutic Drugs In Liver Tumor Cells By Repressing Mdr1 Via Interfering With Nf-Ya, Hongxin Ma, Xuetian Yue, Lifen Gao, Xiaohong Liang, Wenjiang Yan, Zhenyu Zhang, Haixia Shan, Hualin Zhang, Brett T. Spear, Chunhong Ma

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated …