Life Sciences Commons^™

Pseudomonas Pb1-Like Phages: Whole Genomes From Metagenomes Offer Insight Into An Abundant Group Of Bacteriophages, Siobhan C. Watkins, Emily Sible, Catherine Putonti

Biology: Faculty Publications and Other Works

Despite the abundance, ubiquity and impact of environmental viruses, their inherent genomic plasticity and extreme diversity pose significant challenges for the examination of bacteriophages on Earth. Viral metagenomic studies have offered insight into broader aspects of phage ecology and repeatedly uncover genes to which we are currently unable to assign function. A combined effort of phage isolation and metagenomic survey of Chicago’s nearshore waters of Lake Michigan revealed the presence of Pbunaviruses, relatives of the Pseudomonas phage PB1. This prompted our expansive investigation of PB1-like phages. Genomic signatures of PB1-like phages and Pbunaviruses were identified, permitting the unambiguous distinction between …

The Evolution Of Molecular Compatibility Between Bacteriophage Φx174 And Its Host, Alexander Kula, Joseph Saelens, Alyxandria M. Schubert, Michael Travisano, Catherine Putonti

Bioinformatics Faculty Publications

Viruses rely upon their hosts for biosynthesis of viral RNA, DNA and protein. This dependency frequently engenders strong selection for virus genome compatibility with potential hosts, appropriate gene regulation and expression necessary for a successful infection. While bioinformatic studies have shown strong correlations between codon usage in viral and host genomes, the selective factors by which this compatibility evolves remain a matter of conjecture. Engineered to include codons with a lesser usage and/or tRNA abundance within the host, three different attenuated strains of the bacterial virus ФX174 were created and propagated via serial transfers. Molecular sequence data indicate that biosynthetic …

The Evolution Of Molecular Compatibility Between Bacteriophage Φx174 And Its Host, Alexander Kula, Joseph Saelens, Jennifer Cox, Alyxandria M. Schubert, Michael Travisano, Catherine Putonti

Biology: Faculty Publications and Other Works

Viruses rely upon their hosts for biosynthesis of viral RNA, DNA and protein. This dependency frequently engenders strong selection for virus genome compatibility with potential hosts, appropriate gene regulation and expression necessary for a successful infection. While bioinformatic studies have shown strong correlations between codon usage in viral and host genomes, the selective factors by which this compatibility evolves remain a matter of conjecture. Engineered to include codons with a lesser usage and/or tRNA abundance within the host, three different attenuated strains of the bacterial virus ФX174 were created and propagated via serial transfers. Molecular sequence data indicate that biosynthetic …

Gene Co-Occurrence Networks Reflect Bacteriophage Ecology And Evolution, Jason W. Shapiro, Catherine Putonti

Biology: Faculty Publications and Other Works

Bacteriophages are the most abundant and diverse biological entities on the planet, and new phage genomes are being discovered at a rapid pace. As more phage genomes are published, new methods are needed for placing these genomes in an ecological and evolutionary context. Phages are difficult to study by phylogenetic methods, because they exchange genes regularly, and no single gene is conserved across all phages. Here, we demonstrate how gene-level networks can provide a high-resolution view of phage genetic diversity and offer a novel perspective on virus ecology. We focus our analyses on virus host range and show how network …

Molecular Determinants Of Trim5Α Restriction And Recruitment Of Autophagic Effectors, Sabrina Imam

Dissertations

TRIM5α is an anti-viral restriction factor that inhibits the lifecycle of retroviruses. TRIM5α binds to and forms a hexameric lattice around the retroviral capsid, thereby initiating its antiviral activities, which include: (1) inhibition of viral infection; (2) inhibition of viral reverse transcription; (3) disassembly of the capsid; and (4), activation of innate signaling pathways. The formation of this assembly also activates the E3 ubiquitin ligase function of TRIM5α. Ubiquitin modification is associated with directing substrates to particular cellular pathways. We and others have shown that TRIM5α cytoplasmic bodies colocalize with proteins involved in the autophagy pathway, and we hypothesized that …

Uncovering The Mechanisms Underlying The Immunogenicity Of Adenovirus Vaccine Vectors, Natalie Nidetz

Dissertations

Vaccination is historically the most effective tool for preventing infectious disease but current vaccine strategies fail to generate robust immunity to major infectious diseases such as HIV and malaria. Therefore, newer vaccine approaches are needed. Vaccines generated from viral, adenovirus based, vectors (AdVs) have proven highly immunogenic in multiple disease models. However, the clinical use of many AdVs is limited by the presence of pre-existing antibodies in human populations, which prevent expression of antigenic genes during immunization with AdVs based on common adenovirus (Ad) serotypes, such as HAdV-5C. Immunization with rare serotype based AdVs, such as HAdV-28D, are not affected …

Characterizing Immune Response To Hiv-1 Infection In Bicd2-Knockout Cells, Omar Abdel-Rahim

Master's Theses

An important part of the HIV-1 infection cycle is the attachment of the intracellular viral core to the host microtubule network, facilitated by attachment of the viral capsid to cargo adaptor proteins. One such cargo adaptor is Bicaudal D Homolog Protein 2 (BICD2). BICD2 can attach to both the HIV-1 capsid and the dynein/dynactin complex and facilitate the trafficking of the viral core towards the host nucleus. Removal of BICD2 can disrupt this viral translocation, resulting in an elevated immune response that impairs productive HIV-1 infection. In my research, we investigated what viral particles are detected in the absence of …

Understanding The Dynamics Of Protein Lipoylation In Staphylococcus Aureus, Sarah C. Flury

Master's Theses

Staphylococcus aureus is a commensal bacterium that also acts as an opportunistic pathogen. The pathogenicity of S. aureus has often been attributed to the wide range of virulence factors that the bacterium produces. While virulence factors do contribute a great deal, there is a growing field of research that aims to investigate the role of metabolism in bacterial virulence.

My project focuses on the necessity of a metabolic cofactor, lipoic acid. To ensure sufficient amounts of lipoic acid are available for enzyme activity, S. aureus has evolved two pathways to obtain the important nutrient. The lipoic acid salvage pathway is …

Immunobiology Of Adenovirus-Vector Vaccines For Mrsa, Emily Orvis

Master's Theses

Staphylococcus aureus is a gram-positive, extracellular bacterium that has emerged as an

important human pathogen. This bacterium is a leading cause of skin and soft tissue infections

(SSTIs) in humans, often leading to invasive and life-threatening infections. Treatment of S.

aureus infections is becoming more complicated due to the rise of methicillin-resistant S. aureus

(MRSA) strains, which are becoming increasingly resistant to a number of antibiotics. In the

United States, invasive MRSA infections result in more deaths annually than any other infectious

agent.

Despite a dire need, there is currently no vaccine against S. aureus infections. The failure

of past …

Surveying Host Innate Immune Responses To Interferon Antagonist-Deficient Murine Coronaviruses, Aaron Brian Volk

Master's Theses

Two coronaviruses (CoVs)—severe acute respiratory syndrome (SARS) virus and Middle East respiratory syndrome (MERS) virus—have emerged in the 21st century from animal reservoirs into the human population, each causing an epidemic associated with significant disease and mortality. CoV epidemics are currently only controllable by rigorous public health measures; no targeted therapeutics or vaccines exist to treat or prevent any human CoV infection. One method of generating attenuated CoV strains to be studied as vaccine candidates involves specifically disrupting CoV-encoded interferon (IFN) antagonists, thereby rendering the virus vulnerable to host innate antiviral immunity. Deubiquitinating (DUB) activity encoded within CoV nonstructural protein …

Nitric Oxide Inhibits Biofilm Formation By Vibrio Fischeri Via The Nitric Oxide Sensor Hnox, Cecilia Thompson

Dissertations

Nitric oxide (NO) is an important signal secreted by the squid, Euprymna scolopes, and is thought to limit symbiotic biofilm formation, the initial step in colonization by the bacterium, Vibrio fischeri. Previous work demonstrated that a mutant defective for NO-sensor HnoX (heme nitric oxide/oxygen binding) had a competitive advantage over wild-type V. fischeri, but the mechanism by which this occurred remains unknown. HnoX is encoded upstream of hahK, a recently identified positive regulator of biofilm formation. I thus hypothesized that HnoX inhibits colonization by controlling HahK-induced biofilm formation during the initiation of colonization.

I assessed the impact of an hnoX …

Characterizing The Roles Of Staphylococcus Aureus Secreted Factors In Virulence And Modulation Of Innate Immune Cell Activity, Cameron Harvey

Master's Theses

Staphylococcus aureus is a prominent human pathogen that is responsible for a massive burden on healthcare. This thesis takes two approaches to characterize how S. aureus secreted factors subvert the innate immune response. First, characterization of the integral membrane protease 1984 showed that it regulates secretion of a putative lytic transglycosylase, IsaA, which is implicated in virulence. My results suggest IsaA and 1984 are capable of modulating immune responses that result in enhanced heart colonization in vivo. In addition, recent studies have uncovered TLR-independent pathways that induce inflammatory responses after S. aureus insult. Therefore, I hypothesized the bacterium secretes factors …