Microbiology Commons^™

Thymic Stromal Lymphopoietin Participates In The Host Response To Intra-Amniotic Inflammation Leading To Preterm Labor And Birth, Tomi Kanninen, Li Tao, Roberto Romero, Yi Xu, Marcia Arenas-Hernandez, Jose Galaz, Zhenjie Liu, Derek Miller, Dustyn Levenson, Jonathan M. Greenberg, Jonathan Panzer, Justin Padron, Kevin Theis, Nardhy Gomez-Lopez Phd

Medical Student Research Symposium

Objective: To determine if bacteria (Ureaplasma parvum and Sneathia spp.) associated with intra-amniotic infection can trigger the induction of cytokine Thymic stromal lymphopoietin (TSLP) in human amnion epithelial cells (hAECs) in vitro.

Material or subjects: Amniotic fluid and chorioamniotic membrane (CAM) were collected from women with sPTL who delivered at term (n=30) or preterm without intra-amniotic inflammation (n=34), with sterile intra-amniotic inflammation (SIAI, n=27), or with intra-amniotic infection (IAI, n=17). Amnion epithelial cells (AECs), Ureaplasma parvum, and Sneathia spp. were also utilized.

Methods: The expression of TSLP, TSLPR, and IL-7Rα was evaluated in amniotic fluid or CAM by …

Spatial Localization Of Markers And 3d-Cell Model For Study Of The Human Cytomegalovirus Cytoplasmic Virion Assembly Compartment, Taylor Alan Vensko

Wayne State University Theses

Human cytomegalovirus (HCMV) causes severe disease in immunocompromised individuals and is a leading cause of congenital disease. Efficient assembly of virions (viral particles) is an intricate process that requires modulation and modification of host systems. HCMV induces an extensive rearrangement of the cellular endocytic recycling compartment into the site of virion maturation and egress: the cytoplasmic virion assembly compartment (cVAC). The HCMV cVAC is a distinguishing characteristic of infection, although studies have only been performed in traditional cell culture with limited observations in infectedhuman tissues. To study the cVAC, viral and cellular markers that are discrete to their respective compartments …

Rhizobium Symbiotic Capacity Shapes Root-Associated Microbiomes In Soybean, Yuanhui Lu, Bin Ma, Wenfeng Chen, Klaus Schlaeppi, Matthias Erb, Erinne Stirling, Lingfei Hu, Entao Wang, Yunzeng Zhang, Kankan Zhao, Zhijiang Lu, Shudi Ye, Jianming Xu

Environmental Science and Geology Faculty Research Publications

Root-microbiome interactions are of central importance for plant performance and yield. A distinctive feature of legumes is that they engage in symbiosis with N₂-fixing rhizobia. If and how the rhizobial symbiotic capacity modulates root-associated microbiomes are still not yet well understood. We determined root-associated microbiomes of soybean inoculated with wild type (WT) or a noeI mutant of Bradyrhizobium diazoefficiens USDA 110 by amplicon sequencing. UPLC-MS/MS was used to analyze root exudates. The noeI gene is responsible for fucose-methylation of Nod factor secreted by USDA 110 WT strain. Soybean roots inoculated with the noeI mutant showed a significant decrease …

Roles Of A Bradykinin Storm And A Cytokine Storm In Covid-19 Cases, Nouha H. Odeh

Honors College Theses

In the light of recent events, it is imperative to understand the key inflammatory response elements that appear to be the source of more severe ailments resulting from a SARS-CoV-2 viral infection known as Covid-19 The more severe cases of Covid-19 are characterized by a severe inflammatory response resulting in tissue damage. My research proposal aims to investigate the two possible culprits of this response: a bradykinin (BK) storm and an interleukin-6 (IL-6) mediated cytokine storm. In both systems respectively, the excess release of these signals subsequently signals the production of even more of the same response element, resulting in …

Mite Diet Sequences Obtained By High Throughput Sequencing Of Gut Contents Of Freshly Collected Water Mites, Adrian Amelio Vasquez, Obadeh Mohiddin, Zeyu Li, Brittany L. Bonnici, Katherine Gurdziel, Jeffrey L. Ram

Physiology Faculty Research Publications

Cytochrome oxidase subunit I (COI) barcode sequences in this file were obtained from gut DNA extracted from 54 freshly collected water mites, comprising 21 Lebertia quinquemaculosa , 30 Lebertia davidcooki , 1 Limnesia , and 2 Arrenurus specimens. Methods and other details about these sequences are described in a paper by the same authors in a submitted publication (2021: URL to be given here when published). Data on collection locations, primers (mLep and LCOI), amino acid translations, etc. are included in corresponding sequences uploaded to GenBank. The right column below contains additional notes on naming the taxa of the sequences …

The Probiotic Effect Of Clostridium Cochlearium Is Associated With Significant Change In Short-Chain Fatty Acid Metabolism And Gut Microbiota, Qing Ai

Wayne State University Dissertations

The prevalence of obesity is rising steadily across the world, which increases the risk of many metabolic diseases and life-threatening illnesses. A specific strain, Clostridium cochlearium (C. cochlearium), reported as a butyrate producer, could have potential probiotic effects against obesity. The objective of this study was to evaluate the effects of dietary supplementation of C. cochlearium on a high-fat diet-induced obese (DIO) mouse model. The 16S rRNA sequencing of mice gut microbiome was performed at the end of the experimental period to identify the changes in gut microbial composition, investigate possible functional genes, and elucidate potential mechanisms. Thirty-six C57BL/6 6-8 …

Characterization Of Clostridium Cochlearium As A Potential Probiotic For Obesity Management, Paba Edirisuriya

Wayne State University Dissertations

ABSTRACTCHARACTERIZATION OF CLOSTRIDIUM COCHLEARIUM AS A POTENTIAL PROBIOTIC FOR OBESITY MANAGEMENT

ByPABA EDIRISURIYA MAY 2021 Advisor: Dr. Kequan Zhou Major: Nutrition and food science Degree: Doctor of Philosophy Emerging evidence indicates that manipulation of gut microflora is a potential therapeutic approach for managing obesity. Probiotic effects on host weight reduction have repeatedly been revealed through previous studies. Clostridium cochlearium is a butyrate-producing, spore-forming bacteria that have been reported to present in the mammalian gut. Our simulated Invitro digestion model revealed that C. cochlearium could survive in the unfavorable conditions of the human gastrointestinal tract, including low pH (pH2), high bile …

Evaluating Historical Paradigms Of Sterility In Perinatal Microbiology And Ramifications For Pregnancy Outcomes, Jonathan Greenberg

Wayne State University Dissertations

Next-generation sequencing technologies, especially 16S rRNA gene and metagenomic sequencing have allowed investigations of low microbial biomass tissues of the human body. While these sequencing methodologies have provided large amounts of reliable data for higher microbial biomass sites, such as the mouth, intestine, and vagina, tissues of low microbial biomass sites are subject to specific caveats that were not appropriately considered in early investigations of these sites. Low microbial biomass sites of particular interest have included those of the reproductive and urinary systems. Utilization of DNA sequencing methodologies have allowed researchers to challenge existing paradigms of sterility around these sites …

Biological And Computational Studies Of The Structure And Function Of Pul103, A Human Cytomegalovirus Tegument Protein, Ashley N. Anderson

Wayne State University Dissertations

Human cytomegalovirus (HCMV) is an enveloped, single segment, double-stranded DNA virus. HCMV infection causes disease in immunocompromised (HIV patients, transplant recipients) and immunodeficient (fetuses, neonates) populations. Current treatments are effective but are either limited in use or can lead to organ damage and/or antiviral resistance, and no vaccines are available. Additional antiviral targets are needed. HCMV pUL103 is a potential antiviral target. pUL103 is a conserved herpesvirus protein present in the tegument, layer of proteins and RNA between the envelope and capsid of HCMV virions. pUL103 helps reorganize cellular secretory machinery (Golgi, endosomes) to form the cytoplasmic virion assembly compartment …

Functional Analysis Of Bacillus Anthracis Aspartate Transcarbamoylase And Dihydroorotase, Katelyn Leigh Schwager Silva

Wayne State University Theses

There are many enzymes required for efficient and proper pyrimidine biosynthesis. The two that are most important and were discussed in this thesis are aspartate transcarbamoylase (ATCase) and dihydroorotase (DHOase). Both play an important role in not only pyrimidine biosynthesis production, but also mechanistic regulation of de novo synthesis. Anthrax is an infection caused by Bacillus anthracis. Here we studied ATCase and DHOase in Bacillus Anthracis. In this thesis we understood the effects of the enzymes ATCase and DHOase on pyrimidine biosynthesis. Adequate inhibitors of these enzymes would result in cell death and could pose as a cure to infection …

The Effect Of Short-Term Supplementation Of Potato Starch And Vsl#3 On The Large Intestines Of Male C57bl/6 Mice, Kaitlyn R. Merz

Wayne State University Theses

The microbiome is extremely complex and presumed to be involved in several biological processes. Dysbiosis is associated with development of several diseases, therefore, eubiosis is essential for prevention and treatment, possibly achieved through prebiotic or probiotic supplementation. The objective of this study was to establish effects of short-term supplementation on large intestine microbiota, pH and inflammatory cytokines. Large intestines of 21 day old C57BL/6 male mice that were given a control diet or supplemented with 10% potato starch or VSL#3 short-term, were analyzed for shifts in bacteria, pH, and inflammatory cytokine concentration. Large intestine digesta bacteria concentration differed from feces …

Exploring The Short-Term Effects Of Probiotic And Prebiotic Supplementation On The Microbiota And Physiology Of Male C57bl/6 Mice, Miguel Angel Rivas

Wayne State University Theses

The gut microbiome may play a role in the development of chronic diseases like obesity, diabetes, and heart disease. Diets including prebiotics or probiotics can alter the abundance of gut bacterial groups and have subsequent health effects. In this study we wanted to establish a method for comparing the benefits of commercial supplements that alter the microbiota by monitoring fecal microbial profiles in male C57BL/6 mice (n = 24) exposed to 15 days of dietary supplementation. A probiotic diet (VSL#3) and a prebiotic diet (potato starch) were compared to a standard diet (n = 8 for each group). Microbial profiles …

The Role Of Neurokinin Receptors And Satellite Glial Cells In Herpes Simplex Virus 1 Latency, Andrew Jerome

Wayne State University Dissertations

The ability of herpes simplex virus 1 (HSV-1) to establish a lifelong infection in neurons of the trigeminal ganglion (TG) make it a constant public health threat. Viral reactivation from its latent state is currently the leading cause of viral induced blindness in the United State, as well as the leading cause of herpes simplex encephalitis. Unfortunately, how the virus is able to both establish and maintain its latent state in the TG is not well understood. The purpose of this work was to better understand how neuropeptide signaling through neurokinin receptors, as well as how satellite glial cells (SGCs) …

Investigating Antibiotic Resistance In Urban Agricultural Environment Using Phenotypic, Genomic, And Metagenomic Tools, Abdullah Ibn Mafiz

Wayne State University Dissertations

Urban agricultural environment can be an important reservoir of antibiotic resistance and have great food safety and public health indications. This study was to investigate antibiotic-resistant bacteria and antibiotic resistance genes in urban agricultural environment using phenotypic, whole genome sequencing, and metagenomic tools. Three urban community gardens from metro Detroit were studied in two phases.

First phase of this study recovered a total of 207 soil bacteria from 41 soil samples collected from an urban agricultural garden. The most prevalent antibiotic resistance phenotypes demonstrated by Gram-negative bacteria was the resistance to ampicillin (94.2%), followed by chloramphenicol (80.0%), cefoxitin (79.5%), gentamicin …

Investigation Into Roseburia Intesinalis For Optimal Growth And Survivability Conditions For Potential Probiotic Use, Lisa Rana Felczak

Wayne State University Theses

Obesity and diabetes is an epidemic of increasing concern. Certain novel bacteria have been found to be an aid in reversing some of the mechanisms associated. This study focused on investigating the optimal stability conditions for R.intestinalis that can associate with an increase in growth. First, environmental conditions were tested to find the optimal conditions associated with each. Once growth conditions were found, generation time was calculated and various prebiotics were used to investigate a potential for additional growth. Next, common antibiotics were tested to see if the R.intestinalis could still show growth when exposed. Large batches of R.intestinalis were …

The Potential Stimulation Of C. Minuta Growth By Various Prebiotics, And Its Sensitivity To Various Antibiotics, Maria Elena Hakim

Wayne State University Theses

Gut microbiota play a crucial role in maintaining intestinal health and integrity; a feature that is both heritable, as well as affected by the environment and lifestyle. Probiotics are supplements containing live microorganisms that act in a similar manner to gut microflora, and maintain a balance in the latter. C. minuta is a novel bacterium in the gut that was found to be associated with reduction in body weight and adiposity. The aim of this study was to determine the possible effects of different prebiotics on C. minuta growth, and the survival of C. minuta in response to different antibiotics. …

Navigating Human Cytomegalovirus (Hcmv) Envelopment And Egress, William Longeway Close

Wayne State University Dissertations

Human cytomegalovirus (HCMV) is a ubiquitous viral pathogen. In individuals with fully functioning and mature immune systems, HCMV is associated with mild symptoms prior to establishing latency. In individuals with naïve or compromised immune systems, HCMV is capable of causing severe organ damage. HCMV is the leading infectious cause of congenital birth defects and a major non-genetic cause of hearing loss. Unfortunately, antiviral treatment options lack diversity due to limited knowledge of virion replication. If HCMV replication were better understood, new antiviral treatments could be developed.

In this work, we describe the development and implementation of new tools to study …

Biochemical, Structural, And Drug Design Studies Of Norovirus And Zika Virus Proteases, Ben Kuiper

Wayne State University Dissertations

Noroviruses, which are the leading cause of acute gastroenteritis, cause an estimated 677 million infections and 213,000 deaths each year worldwide. Noroviruses are classified into seven genogroups (GI-GVII); GI, GII, and GIV have been shown to be infectious in humans. However, GII noroviruses cause the majority of outbreaks (89%). No pharmacologic treatment or vaccine currently exists to treat or prevent norovirus infections.

Recently, the development of a norovirus replicon system, a murine model of norovirus infection, and the development of a biochemical protease assay have allowed for the design and development of norovirus inhibitors. However, the replicon and biochemical assay …

Human Cytomegalovirus Cytoplasmic Virion Assembly Complex: Structure In Vivo And Role Of Pul103 In Its Biogenesis, Ma Christina Raye Lim

Wayne State University Theses

Human Cytomegalovirus (HCMV) is a linear, double stranded DNA virus that causes severe disease in the immunocompromised, and is one of the common cause of congenital disease. Antivirals that are currently available for treatment target the DNA replication of the virus cycle, and are highly toxic. Finding new drug targets, such as proteins responsible for virion assembly and egress, would help to alleviate the disease burden.

HCMV remodels the host cell to form a structure called the cytoplasmic virion assembly complex (cVAC), a site of virion maturation and egress. The first objective of this work is to study the structure …

The Roles Of Human Cytomegalovirus Tegument Proteins Pul48 And Pul103 During Lytic Infection, Daniel Angel Ortiz

Wayne State University Dissertations

THE ROLES OF HUMAN CYTOMEGALOVIRUS TEGUMENT PROTEINS pUL48 AND pUL103 DURING LYTIC INFECTION

by

DANIEL A. ORTIZ

December 2015

Advisor: Dr. Philip E. Pellett

Major: Immunology and Microbiology

Degree: Doctor of Philosophy

Human cytomegalovirus (HCMV) is a large double-stranded DNA virus that causes severe disease in newborns and immunocompromised patients. During infection, HCMV is able to reconfigure the host cell machinery to establish a virus producing factory, termed the cytoplasmic virion assembly complex (cVAC). Generating drugs that affect cVAC development or function provides an alternative mode of action for HCMV antivirals that can essentially eliminate virion production. The objective of …

Role Of Crebh In Endotoxin Mediated Modulation Of Hepatic Metabolism, Aditya Prakash Dandekar

Wayne State University Dissertations

Bacterial endotoxins can induce a variety of physiological changes in the host. This effect is not only restricted to inflammatory changes but also comprises metabolic changes in the host body. Lipopolysaccharide (LPS), one of the key components of the bacterial cell walls, is capable of triggering host metabolic changes. Hyperlipidemia usually accompanies with high endotoxin levels as well as inflammation. Lipid metabolism disorders are one of the common hallmarks of a patient with sepsis or high levels of endotoxin through diet. Previously, we have identified an endoplasmic reticulum (ER) anchored liver-specific transcription factor CREBH (cAMP-responsive element-binding protein, hepatocyte-specific), which is …

Characterization Of Oral Microbiota In Xerostomic Versus Non-Xerostomic Volunteers And In Daily Samples Following Standard Oral Hygiene Practices, Chelsea Myers

Wayne State University Theses

A thesis presented on the characterization of oral microbiota in xerostomic versus non-xerostomic volunteers and in daily samples following standard oral hygiene practices. Xerostomia is a difficult and burdensome disease that can be very difficult to diagnose. Understanding the oral microbiota between these diseased and healthy (non-xerostomic) can give us great insight on new treatments and/or prevention. Goals of the study included determining whether there substantial differences in oral microbial populations between the two groups, and whether varying nightly oral hygiene practices had an impact on next-morning oral microbiota titers or composition. Microbial loads were determined by qPCR using broad-spectrum …

The Effects Of Motility And Chemotaxis On Vibrio Cholerae Colonization In Zebrafish, Paula Dietz

Wayne State University Theses

Vibrio cholerae, the cause of the diarrheal disease cholera, is a gram-negative, curved rod-shaped bacterium, with a single polar flagellum. V. cholerae is naturally found in aquatic environments and is highly motile. When it enters a human host, V. cholerae uses flagellar motility to pass through the stomach and into the small intestine. Once in the small intestine, motility genes are downregulated and virulence gene expression is upregulated. V. cholerae motility and chemotaxis effects have not yet been studied in a zebrafish model, a natural host of this bacterium. We hypothesize that V. cholerae in frame deletions of vital motility …

Hiv Integrase Mechanisms Of Resistance To Raltegravir, Elvitegravir, And Dolutegravir, Kyla Nicole Ross

Wayne State University Theses

ABSTRACT

HIV INTEGRASE MECHANISMS OF RESISTANCE TO RALTEGRAVIR, ELVITEGRAVIR, AND DOLUTEGRAVIR

by

KYLA ROSS

December 2015

Advisor: Dr. Ladislau Kovari

Major: Biochemistry and Molecular Biology

Degree: Master of Science

HIV-1 integrase (HIV-1 IN or IN) is a multimeric enzyme that integrates the HIV-1 genome into the chromosomes of infected CD4+ T-cells. Currently there are three FDA approved HIV-1 IN strand transfer inhibitors (INSTIs) used in clinical practice: raltegravir (RAL), elvitegravir (ELV), and dolutegravir (DTG). The [Q148H], [Q148H, G140S], [Q148R], [Q148R, G140A] and [N155H, E92Q] mutations decrease IN susceptibility to RAL and ELV and may result in therapeutic failure. As an …

Antimicrobial-Resistant Listeria Species From Retail Meat In Metro Detroit, Liziane Da Rocha

Wayne State University Theses

A total of 138 Listeria isolates, including 58 Listeria welshimeri, 44 Listeria monocytogenes, and 36 Listeria innocua, from retail meat were characterized by antimicrobial susceptibility tests against nine antimicrobials. In addition, the 44 L. monocytogenes were analyzed by serotype identification using PCR and genotyping using pulsed-filed gel electrophoresis (PFGE). Resistance to one or two antimicrobials was observed in 32 Listeria (23.2%). No multidrug resistance was identified. Tetracycline resistance was the most common resistance phenotype and identified in 22 Listeria isolates. Low prevalence of resistance to ciprofloxacin, erythromycin, gentamicin, and vancomycin was also detected. L. innocua demonstrated the highest overall prevalence …

The Antimicrobial, Mechanical, Physical And Structural Properties Of Chitosan-Gallic Acid Films, Xiuxiu Sun, Zhe Wang, Hoda Kadouh, Kequan Zhou

Nutrition and Food Science Faculty Research Publications

Chitosan films incorporated with various concentrations of gallic acid were prepared and investigated for antimicrobial, mechanical, physical and structural properties. Four bacterial strains that commonly contaminate food products were chosen as target bacteria to evaluate the antimicrobial activity of the prepared gallic acid-chitosan films. The incorporation of gallic acid significantly increased the antimicrobial activities of the films against Escherichia coli, Salmonella typhimurium, Listeria innocua and Bacillus subtilis. Chitosan films incorporated with 1.5 g/100 g gallic acid showed the strongest antimicrobial activity. It was also found that tensile strength (TS) of chitosan film was significantly increased when incorporating …

Deletion Of The Human Cytomegalovirus Us17 Gene Increases The Ratio Of Genomes Per Infectious Unit And Alters Regulation Of Immune And Endoplasmic Reticulum Stress Response Genes At Early And Late Times After Infection, Stephen James Gurczynski, Subhendu Das, Philip E. Pellett

Immunology and Microbiology Faculty Research Publications

Human cytomegalovirus (HCMV) employs numerous strategies to combat, subvert, or co-opt host immunity. One evolutionary strategy for this involves capture of a host gene and then its successive duplication and divergence, forming a family of genes, many of which have immunomodulatory activities. The HCMV US12 family consists of 10 tandemly arranged sequence-related genes in the unique short (US) region of the HCMV genome (US12 to US21). Each gene encodes a protein possessing seven predicted transmembrane domains, patches of sequence similarity with cellular G-protein-coupled receptors, and the Bax inhibitor 1 family of antiapoptotic proteins. We show that one member, US17, plays …

Mechanisms For Bicarbonate-Mediated Virulence In Vibrio Cholerae, Joshua James Thomson

Wayne State University Dissertations

Vibrio cholerae is the etiologic agent of the severe diarrheal disease cholera. The aquatic bacterium is ingested by humans through contaminated water or food. Disease initiation depends on the production of the major virulence factors: cholera toxin (CT) and the toxin co-regulated pilus (TCP). The bacterium responds to signals in the human host that activate a virulence regulatory cascade termed the "ToxR Regulon". The ToxR regulon consists of various transcription regulators whose activity culminates in the production of the major virulence regulator, ToxT. ToxT directly activates transcription of CT and TCP, as well as many other gene products involved in …

Targeting Cxcr4 With Ctce-9908 Inhibits Prostate Tumor Metastasis, Donald Wong, Pridvi Kandagatla, Walter Korz, Sreenivasa R. Chinni

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

CXCL12/CXCR4 transactivation of epidermal growth factor family receptors in lipid raft membrane microdomains on cell surface is thought to mediate tumor growth and subsequent development of metastatic disease. CTCE-9908 is a known inhibitor of CXCR4. Herein, we tested the efficacy of CTCE-9908 in inhibiting prostate cancer cell growth, invasion, and metastasis.

Methods

We used a panel ofin vitroassays utilizing human prostate cancer cell lines and anin vivoorthotopic prostate cancer model to assess the anti-tumoral activity of CTCE-9908.

Results

We demonstrated that (a) CTCE-9908 treatment resulted in no significant change in the growth of PC-3 and C4-2B cells; (b) …

Recombinant Interleukin-21 Plus Sorafenib For Metastatic Renal Cell Carcinoma: A Phase 1/2 Study, Shailender Bhatia, Brendan, Marc S. Ernstoff, Michael, Elisabeth I. Heath, Wilson H. Miller Jr, Igor Puzanov, David I. Quinn, Thomas, Peter Vanveldhuizen, Kelly, Jeremy, Rachel, Naomi, Sonia, John A. Thompson

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Despite the positive impact of targeted therapies on metastatic renal cell carcinoma (mRCC), durable responses are infrequent and an unmet need exists for novel therapies with distinct mechanisms of action. We investigated the combination of recombinant Interleukin 21 (IL-21), a cytokine with unique immunostimulatory properties, plus sorafenib, a VEGFR tyrosine kinase inhibitor.

Methods

In this phase 1/2 study, 52 mRCC patients received outpatient treatment with oral sorafenib 400 mg twice daily plus intravenous IL-21 (10–50 mcg/kg) on days 1–5 and 15–19 of each 7-week treatment course. The safety, antitumor activity, pharmacokinetic and pharmacodynamic effects of the combination were …