Life Sciences Commons^™

The Antimicrobial Activity And Cellular Pathways Targeted By P-Anisaldehyde And Epigallocatechin Gallate In The Opportunistic Human Pathogen Pseudomonas Aeruginosa, Yetunde Adewumni, Sanchirmaa Namjilsuren, William D. Walker, Dahlia N. Amato, Douglas V. Amato, Olga V. Mavrodi, Derek L. Patton, Dmitri V. Mavrodi

Faculty Publications

Plant-derived aldehydes are constituents of essential oils that possess broad-spectrum antimicrobial activity and kill microorganisms without promoting resistance. In our previous study, we incorporated p-anisaldehyde from star anise into a polymer network called PANDAs (Pro-Antimicrobial Networks via Degradable Acetals) and used it as a novel drug delivery platform. PANDAs released p-anisaldehyde upon a change in pH and humidity, and controlled growth of the multi-drug resistant pathogen Pseudomonas aeruginosa PAO1. In this study, we identified cellular pathways targeted by p-anisaldehyde, by generating 10,000 transposon mutants of PAO1 and screened them for hypersensitivity to p-anisaldehyde. To improve the …

The Thiol Specific Antioxidant (Tsa1) Gene Is Required For Survival In Macrophages And Oxidative Stress Resistance In Histoplasma Capsulatum, Lauren Kennedy

Master's Theses

Histoplasma capsulatum(Hc) is a pathogenic fungus that causes one of the most common invasive fungal respiratory diseases, Histoplasmosis. Histoplasmaundergoes a dimorphic shift from mold to yeast which is crucial to pathogenesis of the organism.

The thiol specific antioxidant gene, Tsa1,is strongly upregulated in the yeast (pathogenic) morphotype. This data led to the hypothesis that this gene plays a role in protecting Hcfrom host mediated oxidative attack. To characterize Tsa1 function, a knockdown strain (tsa1-RNAi) was created by RNAi gene silencing. Expression of Tsa1in the tsa1-RNAistrain was reduced to 10% that …

The Effect Of Historic Shipwrecks On Sediment Microbiomes In The Northern Gulf Of Mexico, Melissa Brock

Master's Theses

Microorganisms are ubiquitously distributed across all aquatic habitats, but it is the environmental conditions of a habitat that determine which microorganisms can thrive in terms of abundance or metabolic activity. Habitats that experience consistent physical and chemical environmental conditions repeatedly favor specific taxonomic groups which may result in a microbial assemblage that is commonly associated with that habitat (i.e., a core microbiome). Core microbiomes have been identified for a variety of natural marine habitats including methane seeps, wood falls, octocoral, and deep-sea sediments. However, it was unknown if the presence of man-made structures on the seafloor, including historic shipwrecks, also …

The Histoplasma Capsulatum Ddr48 Gene Is Required For Survival Within Macrophages And Resistance To Oxidative Stress And Antifungal Drugs, Logan Blancett

Dissertations

Histoplasma capsulatum(Hc)is a systemic, dimorphic fungal pathogen that affects upwards of 500,000 individuals in the United States annually. Hc grows as a multicellular mold at environmental temperatures; whereas, upon inhalation into a human or other mammalian host, it transforms into a unicellular, pathogenic yeast. The research presented in this dissertation is focused on characterizing the DNA damage-responsive gene HcDDR48. HcDDR48was originally isolated via a subtractive DNA library enriched for transcripts enriched in the mold-phase of Hcgrowth. Upon further analysis we found that HcDDR48is not just expressed in the mold morphotype, but both growth programs …

The Antimicrobial Activity And Cellular Targets Of Plant Derived Aldehydes And Degradable Pro-Antimicrobial Networks In Pseudomonas Aeruginosa, Yetunde Adewunmi

Dissertations

Essential oils (EOs) are plant-derived products that have been long exploited for their antimicrobial activities in medicine, agriculture, and food preservation. EOs represent a promising alternative to conventional antibiotics due to the broad-range antimicrobial activity, low toxicity to human commensal bacteria, and the capacity to kill microorganisms without promoting resistance. Despite the progress in the understanding of the biological activity of EOs, many aspects of their mode of action remain inconclusive. The overarching aim of this work was to address these gaps by studying molecular interactions between antimicrobial plant aldehydes and the opportunistic human pathogen Pseudomonas aeruginosa. We initiated …

Analysis Of The Cody Rnome Reveals Rsad As A Stress-Responsive Riboregulator Of Overflow Metabolism In Staphylococcus Aureus, Yoann Augagneur, Alyssa N. King, Noëlla Germain-Amiot, Mohamed Sassi, John W. Fitzgerald, Gyan S. Sahukhal, Mohamed O. Elasri, Brice Felden, Shaun R. Brinsmade

Faculty Publications

In Staphylococcus aureus, the transcription factor CodY modulates the expression of hundreds of genes, including most virulence factors, in response to the availability of key nutrients like GTP and branched‐chain amino acids. Despite numerous studies examining how CodY controls gene expression directly or indirectly, virtually nothing is known about the extent to which CodY exerts its effect through small regulatory RNAs (sRNAs). Herein, we report the first set of sRNAs under the control of CodY. We reveal that staphylococcal sRNA RsaD is overexpressed >20‐fold in a CodY‐deficient strain in three S. aureus clinical isolates and in S. epidermidis. …

Current Understanding Of West Nile Virus Clinical Manifestations, Immune Responses, Neuroinvasion, And Immunotherapeutic Implications, Fengwei Bai, E. Ashley Thompson, Parminder J.S. Vig, A. Arturo Leis

Faculty Publications

West Nile virus (WNV) is the most common mosquito-borne virus in North America. WNV-associated neuroinvasive disease affects all ages, although elderly and immunocompromised individuals are particularly at risk. WNV neuroinvasive disease has killed over 2300 Americans since WNV entered into the United States in the New York City outbreak of 1999. Despite 20 years of intensive laboratory and clinical research, there are still no approved vaccines or antivirals available for human use. However, rapid progress has been made in both understanding the pathogenesis of WNV and treatment in clinical practices. This review summarizes our current understanding of WNV infection in …

Parasitic Microbiome Project: Grand Challenges, Nolwenn M. Dheilly, Joaquín Martínez Martínez, Karyna Rosario, Paul J. Brindley, Raina N. Fichorava, Jonathan Z. Kaye, Kevin D. Kohl, Laura J. Knoll, Julius Lukeš, Susan L. Perkins, Robert Poulin, Lynn Schriml, Luke R. Thompson

Faculty Publications

No abstract provided.

The Evolutionary Diversity And Biological Function Of Phenazine Metabolite Biosynthesis In Burkholderia Spp, Samuel Hendry

Master's Theses

Burkholderia encompass a group of ubiquitous Gram-negative bacteria that include numerous saprophytes, as well as several species that cause infections in animals, immunocompromised patients, and plants. Some species of Burkholderia produce colored redox-active secondary metabolites called phenazines (Phz). In the model opportunistic pathogen Pseudomonas aeruginosa, phenazines strongly contribute to the competitiveness, formation of biofilms, and virulence in multiple models of infection. Similar depth of knowledge on the diversity, biosynthesis, and biological functions of phenazines in Burkholderiais missing. This project aimed to bridge this gap in knowledge by focusing on phenazine pathways of B. lata and closely related …

The Importance Of Rnd-Type Efflux Pumps In The Interactions Of Pseudomonas Aeruginosa With 4-Methoxybenzaldehyde, Sanchirmaa Namjilsuren

Honors Theses

Pseudomonas aeruginosa is a common hospital-acquired pathogen and is often associated with high mortality rates due to the development of multidrug-resistance. Antimicrobial plant-derived (phyto-) aldehydes present a promising alternative to antibiotics due to their broad-spectrum antimicrobial activity and low propensity to trigger resistance. However, two main problems preclude the widespread application of these compounds: chemical instability and low antimicrobial efficacy. The ongoing collaboration between the Mavrodi and Patton labs at USM has recently addressed the problem of chemical instability by incorporating plant aldehydes into polymer materials called Pro-Antimicrobial Networks via Degradable Acetals (PANDAs). Thus, this study aimed to address the …

The Impact Of Oxygen On The Intracellular Survival Of Listeria Monocytogenes, Amber N. Coats

Honors Theses

Listeria monocytogenes is an intracellular pathogen that is responsible for the foodborne disease listeriosis. In order to invade host cells and establish an infection, this pathogen must travel through the gastrointestinal tract where it is exposed to a variety of stressors, including low pH, bile, and variations in oxygen concentrations. These stressors necessitate this organism’s ability to sense and respond to its environment. Previous research has shown that bacteria use two-component systems to sense and regulate genes needed for improved survival in stressful environmental conditions. The goal of this study was to determine if the expression of the putative oxygen …

Establishment Of Listeria Monocytogenes In The Gastrointestinal Tract, Morgan L. Davis, Steven C. Ricke, Janet R. Donaldson

Faculty Publications

Listeria monocytogenes is a Gram positive foodborne pathogen that can colonize the gastrointestinal tract of a number of hosts, including humans. These environments contain numerous stressors such as bile, low oxygen and acidic pH, which may impact the level of colonization and persistence of this organism within the GI tract. The ability of L. monocytogenes to establish infections and colonize the gastrointestinal tract is directly related to its ability to overcome these stressors, which is mediated by the efficient expression of several stress response mechanisms during its passage. This review will focus upon how and when this occurs and how …

A Novel Sparse Compositional Technique Reveals Microbial Perturbations, Cameron Martino, James T. Morton, Clarisse A. Martoz, Luke R. Thompson, Anupriya Tripathi, Rob Knight, Karsten Zengler

Faculty Publications

The central aims of many host or environmental microbiome studies are to elucidate factors associated with microbial community compositions and to relate microbial features to outcomes. However, these aims are often complicated by difficulties stemming from high-dimensionality, non-normality, sparsity, and the compositional nature of microbiome data sets. A key tool in microbiome analysis is beta diversity, defined by the distances between microbial samples. Many different distance metrics have been proposed, all with varying discriminatory power on data with differing characteristics. Here, we propose a compositional beta diversity metric rooted in a centered log-ratio transformation and matrix completion called robust Aitchison …