Medical Microbiology Commons^™

Effects Of Interleukin-22 (Il-22) On Necroptosis, Inflammatory Responses, And Metabolism Of Mycobacterium Tuberculosis Stimulated Type 2 Diabetes Mellitus Mouse Macrophages, Bismark Owusu-Afriyie

Biotechnology Theses

Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and causes nearly 1.3 million deaths per year. Limited information is available about the immune responses during Mtb infection in type 2 diabetic hosts. Our laboratory developed an experimentally induced type 2 diabetes (T2DM) model in wild-type C57BL/6 mice and found that IL-22 and type 3 innate lymphoid cells (ILC3s) reduce inflammation and mortality of Mtb-infected T2DM mice. Our laboratory also found that Mtb-infected alveolar macrophages (AMs) from T2DM mice undergo necroptosis compared to Mtb-infected AMs of non-T2DM mice. In the current study, we determined whether …

Aging Manuka Honey Improves Antimicrobial Activity Against Pathogenic Bacteria, Rayna M. Carlson

2023 Symposium

Manuka honey (MH) has been documented to possess powerful anti-microbial properties through multiple mechanisms. These mechanisms include a low pH, high osmolarity, iron chelation, and its unique manuka factor (UMF), methylglyoxal (MGO). Although MGO is purported to be a major pillar in the honey’s antimicrobial properties, its activity is variable against different bacterial species. We hypothesize that MH’s other antimicrobial mechanisms may also exhibit variable activity against different bacterial species. Preliminary experiments to determine the Manuka honey minimum inhibitory concentrations (MIC) for bacterial species, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, suggested that some Manuka honey antimicrobial mechanisms …

Stewardship Opportunities For Cervical Lymphadenitis And Deep Neck Space Abscesses, Aaron Shaw, Brian R. Lee, Lauren Kazmaier, Emily Baker, Tina Dao, Sandra Arnold, Angela Myers

Research Days

Background: Cervical lymphadenitis (LAD) and deep neck space abscesses (DNSA) are common pediatric infections caused by similar bacteria. We sought to determine differences in presentation, diagnosis, and treatment between LAD and DNSA to identify antimicrobial and diagnostic stewardship opportunities.

Methods: Charts were obtained using ICD9/10 codes for retropharyngeal and parapharyngeal abscessed (DNSA), and LAD between 1/1/10-12/31/20 from two pediatric centers. 1981 charts were identified. Charts were excluded if the diagnosis was not a bacterial infection (e.g. Kawasaki disease), if the LAD was not in the neck, or if caused by less common bacteria (e.g. tuberculosis). Data on presenting signs, symptoms, …

Oxidative Stress And Micrornas In Endothelial Cells Under Metabolic Disorders, Morgan Minjares, Wendy Wu, Jie-Mei Wang

Pharmaceutical Sciences Faculty Publications

Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced …

Multiple And Consecutive Genome Editing Using I-Gonad And Breeding Enrichment Facilitates The Production Of Genetically Modified Mice, Carolina R Melo-Silva, Cory J Knudson, Lingjuan Tang, Samita Kafle, Lauren E. Springer, Jihae Choi, Christopher M. Snyder, Yajing Wang, Sangwon V. Kim, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

Genetically modified (GM) mice are essential tools in biomedical research. Traditional methods for generating GM mice are expensive and require specialized personnel and equipment. The use of clustered regularly interspaced short palindromic repeats (CRISPR) coupled with improved-Genome editing via Oviductal Nucleic Acids Delivery (i-GONAD) has highly increased the feasibility of producing GM mice in research laboratories. However, genetic modification in inbred mouse strains of interest such as C57BL/6 (B6) is still challenging because of their low fertility and embryo fragility. We have successfully generated multiple novel GM mouse strains in the B6 background while attempting to optimize i-GONAD. We found …

Investigating Differences In Iga Antibody Response Against Aspergillus Fumigatus In Wild Type And Tlr7 Protein Deficient Mice, Courtney Folk

Student Academic Conference

Aspergillus fumigatus is a commonly inhaled, respiratory fungal pathogen and an allergen found in flooded indoor environments, household dust, soil, and plant matter. While a competent immune system effectively clears the inhaled fungus, this same fungus poses a significant threat to weakened immune systems due to its potential to invade the lungs, bloodstream and brain tissue. The mouse genome is 99% similar to the human genome and can serve effectively model the effects of inhaled A. fumigatus (Guénet, 2005). Antibodies play a crucial role in neutralizing pathogens and in mediating an allergic response. In this study, we will investigate the …

Moerv14 Mediates The Intracellular Transport Of Cell Membrane Receptors To Govern The Appressorial Formation And Pathogenicity Of Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Magnaporthe oryzae causes rice blasts posing serious threats to food security worldwide. During infection, M. oryzae utilizes several transmembrane receptor proteins that sense cell surface cues to induce highly specialized infectious structures called appressoria. However, little is known about the mechanisms of intracellular receptor tracking and their function. Here, we described that disrupting the coat protein complex II (COPII) cargo protein MoErv14 severely affects appressorium formation and pathogenicity as the ΔMoerv14 mutant is defective not only in cAMP production but also in the phosphorylation of the mitogen-activated protein kinase (MAPK) MoPmk1. Studies also showed that either externally supplementing cAMP or …

Characterization Of Manganese-Induced Neurodegenration In C. Elegans Treated With Winterberry Leaf Extract, Brendan Moline

Honors College

Neurodegeneration is a condition present in Alzheimer’s disease (AD) and Parkinson’s disease (PD) in which the cells of the nervous system experience loss of function and death. Around the world, each year PD and AD affect 6.2 million and 29.8 million people, respectively, with the exact causes remaining unknown. Manganese (Mn) is a transition metal which is essential for human survival in trace concentrations. However, overexposure to Mn can induce neurodegeneration through the accumulation of reactive oxygen species and the eventual onset of oxidative stress. An extract produced from winterberry leaves (Ilex verticillata) exhibits antioxidant properties as it has been …

Hpv-Related Anal Cancer Is Associated With Changes In The Anorectal Microbiome During Cancer Development, Jacob H. Elnaggar, Victoria O. Huynh, Daniel Lin, R. Tyler Hillman, Chike O. Abana, Molly B. El Alam, Katarina C. Tomasic, Tatiana V. Karpinets, Ramez Kouzy, Jae L. Phan, Jennifer Wargo, Emma B. Holliday, Prajnan Das, Melissa P. Mezzari, Nadim J. Ajami, Erica J. Lynn, Bruce D. Minsky, Van K. Morris, Andrea Milbourne, Craig A. Messick, Ann H. Klopp, P. Andrew Futreal, Cullen M. Taniguchi, Kathleen M. Schmeler, Lauren E. Colbert

School of Graduate Studies Faculty Publications

Background: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease. Methods: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade …

Design And Preclinical Evaluation Of A Universal Sars-Cov-2 Mrna Vaccine, Jane Qin, Ju Hyeong Jeon, Jiangsheng Xu, Laura Katherine Langston, Ramesh Marasini, Stephanie Mou, Brian Montoya, Carolina R Melo-Silva, Hyo Jin Jeon, Tianyi Zhu, Luis J. Sigal, Renhuan Xu, Huabin Zhu

Department of Microbiology and Immunology Faculty Papers

Because of the rapid mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective vaccine against SARS-CoV-2 variants is needed to prevent coronavirus disease 2019 (COVID-19). T cells, in addition to neutralizing antibodies, are an important component of naturally acquired protective immunity, and a number of studies have shown that T cells induced by natural infection or vaccination contribute significantly to protection against several viral infections including SARS-CoV-2. However, it has never been tested whether a T cell-inducing vaccine can provide significant protection against SARS-CoV-2 infection in the absence of preexisting antibodies. In this study, we designed and evaluated …

Topical Anesthetic Gel Interferes With Antibacterial Efficacy Of Povidone-Iodine Both In Vitro And In Vivo, Cecilly Kelleher Bs, Jacob Im Md, Linda Kang Bs, Aleksey Mishulin Md, Sukhvinder Singh Phd, Ashok Kumar Phd

Medical Student Research Symposium

Purpose: To evaluate the effects of viscous lidocaine gel on the antimicrobial efficacy of povidone-iodine (PI) and their order of application in both in vitro and in vivo models.

Methods: In vitro antibacterial effects were tested against Staphylococcus aureus (S. aureus) with disc diffusion methods for application of lidocaine alone, PI alone, PI before lidocaine, and lidocaine before PI. Zones of inhibition were measured after incubation at 37°C overnight. Mouse eyes were colonized with S. aureus for in vivo study to which PI and/or lidocaine were applied in various combinations. Eyes were then rinsed with saline, and …

Development Of Bacteriophage Therapy For Novel Treatment Of Bacterial Infections, Terry Ann Else, Guadalupe Mercado

Annual Research Symposium

No abstract provided.

Intestinal Neuropod Cell Gucy2c Regulates Visceral Pain, Joshua R. Barton, Annie K. Londregran, Tyler D. Alexander, Ariana A. Entezari, Shely Bar-Ad, Lan Cheng, Angelo C. Lepore, Adam E. Snook, Manuel Covarrubias, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Visceral pain (VP) is a global problem with complex etiologies and limited therapeutic options. Guanylyl cyclase C (GUCY2C), an intestinal receptor producing cyclic GMP(cGMP), which regulates luminal fluid secretion, has emerged as a therapeutic target for VP. Indeed, FDA-approved GUCY2C agonists ameliorate VP in patients with chronic constipation syndromes, although analgesic mechanisms remain obscure. Here, we revealed that intestinal GUCY2C was selectively enriched in neuropod cells, a type of enteroendocrine cell that synapses with submucosal neurons in mice and humans. GUCY2Chi neuropod cells associated with cocultured dorsal root ganglia neurons and induced hyperexcitability, reducing the rheobase and increasing the resulting …

Effects Of Adjuvants In A Rabies-Vectored Ebola Virus Vaccine On Protection From Surrogate Challenge, Catherine Yankowski, Drishya Kurup, Christoph Wirblich, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Ebola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50-90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus glycoprotein. FILORAB1 is immunogenic and protective from Ebola virus challenge in mice and non-human primates, and protection is enhanced when formulated with toll-like receptor 4 agonist Glucopyranosyl lipid adjuvant (GLA) in a squalene oil-in-water emulsion (SE). Through an adjuvant comparison in mice, we demonstrate that GLA-SE improves FILORAB1 efficacy by activating the innate immune system and shaping …

Chlamydia Trachomatis Subverts Alpha-Actinins To Stabilize Its Inclusion, A. Haines, J. Wesolowski, F. Paumet

Department of Microbiology and Immunology Faculty Papers

Chlamydia trachomatis is the leading cause of sexually transmitted bacterial disease and a global health burden. As an obligate intracellular pathogen, Chlamydia has evolved many strategies to manipulate its host and establish its intracellular niche called the inclusion. C. trachomatis reorganizes the host actin cytoskeleton to form scaffolds around the inclusion and reinforce the growing inclusion membrane. To control the kinetics and formation of actin scaffolds, Chlamydia expresses the effector InaC/CT813, which activates the host GTPase RhoA. Here, we have discovered that InaC stabilizes actin scaffolds through the host actin cross-linking proteins α-actinins 1 and 4. We demonstrate that α-actinins …

A Rodent Model For Dirofilaria Immitis, Canine Heartworm: Parasite Growth, Development, And Drug Sensitivity In Nsg Mice, Jessica A. Hess, Mark L. Eberhard, Marcelo Segura-Lepe, Kathrin Grundner-Culemann, Barbara Kracher, Jeffrey Shryock, John Harrington, David Abraham

Department of Microbiology and Immunology Faculty Papers

Heartworm disease, caused by Dirofilaria immitis, remains a significant threat to canines and felines. The development of parasites resistant to macrocyclic lactones (ML) has created a significant challenge to the control of the infection. The goal of this study was to determine if mice lacking a functional immune response would be susceptible to D. immitis. Immunodeficient NSG mice were susceptible to the infection, sustaining parasites for at least 15 weeks, with infective third-stage larvae molting and developing into the late fourth-stage larvae. Proteomic analysis of host responses to the infection revealed a complex pattern of changes after infection, with at …

Identification Of Collaborative Cross Mouse Strains Permissive To Salmonella Enterica Serovar Typhi Infection, Kishore Alugupalli, Sudeep Kothari, Matthew P Cravens, Justin A Walker, Darren T Dougharty, Gregory S. Dickinson, Louis A Gatto, Andreas J Bäumler, Tamding Wangdi, Darla R Miller, Fernando Pardo-Manuel De Villena, Linda D Siracusa

Department of Microbiology and Immunology Faculty Papers

Salmonella enterica serovar Typhi is the causative agent of typhoid fever restricted to humans and does not replicate in commonly used inbred mice. Genetic variation in humans is far greater and more complex than that in a single inbred strain of mice. The Collaborative Cross (CC) is a large panel of recombinant inbred strains which has a wider range of genetic diversity than laboratory inbred mouse strains. We found that the CC003/Unc and CC053/Unc strains are permissive to intraperitoneal but not oral route of S. Typhi infection and show histopathological changes characteristic of human typhoid. These CC strains are immunocompetent, …

Bacteria Commonly Associated With Central Nervous System Catheter Infections Elicit Distinct Csf Proteome Signatures, Matthew K. Beaver, Dragana Noe, Ishwor Thapa, Hesham Ali, Jessica Snowden, Tammy Kielian, Gwenn Skar

Journal Articles: Pathology and Microbiology

Background: Cerebrospinal fluid (CSF) shunt infection is a common and devastating complication of the treatment of hydrocephalus. Timely and accurate diagnosis is essential as these infections can lead to long-term neurologic consequences including seizures, decreased intelligence quotient (IQ) and impaired school performance in children. Currently the diagnosis of shunt infection relies on bacterial culture; however, culture is not always accurate since these infections are frequently caused by bacteria capable of forming biofilms, such as Staphylococcus epidermidis, Cutibacterium acnes, and Pseudomonas aeruginosa resulting in few planktonic bacteria detectable in the CSF. Therefore, there is a critical need to identify a …

Inpatient Management Of An Intravenous Drug User With Tetanus, Nina Paris

Capstone Showcase

Tetanus is rare in the United States now due to the tetanus vaccine but there is still the potential too see patients with tetanus. IV drug users, neonates, and geriatric populations are at an increased risk of developing tetanus. Tetanus is caused by Clostridium tetani, a spore forming and exotoxin releasing anaerobic bacteria. The symptoms of tetanus are caused by the exotoxin tetanospasmin which inhibits the release of inhibitory neurotransmitters, leading to sustained neuronal stimulation. The classic symptoms of tetanus are lockjaw (trismus), neck stiffness, back arching, and fever. Patients can be febrile, tachycardic, tachypneic, and hypertensive on exam. …

Combatting Bacterial Infections: The Efficacy Of Poly-Gamma-Glutamic Acid On The Prevention Of Nasopharyngeal Infections Among Individuals With Cleft Lip And Palate, Florence Pun

Scripps Senior Theses

Cleft lip and palate (CLP) is a medical condition where children are born with an unfused lip and palate. While surgery is required to fuse the lip and palate, there are other conditions that children with CLP face after surgeries, such as otitis media (OM), speech impediments, and difficulty breathing. Particularly, OM occurs frequently in individuals with CLP because the tensor veli palatini muscles cannot open the Eustachian tube frequently and ventilate the middle ear properly, even after surgery. This thesis is a research proposal to evaluate whether γ-PGA can be used in nasal washes to safely prevent nasopharyngeal infections …