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Item A common parasite could one day deliver drugs to the brain − how scientists are turning Toxoplasma gondii from foe into friend(The Conversation US, Inc., 2024-08-07) Sullivan, BillItem Associations Between Dysmenorrhea Symptom-Based Phenotypes and Vaginal Microbiome: A Pilot Study(Wolters Kluwer, 2021) Chen, Chen X.; Carpenter, Janet S.; Gao, Xiang; Toh, Evelyn; Dong, Qunfeng; Nelson, David E.; Mitchell, Caroline; Fortenberry, J. DennisBACKGROUND: Dysmenorrhea is highly prevalent; it places women at risk for other chronic pain conditions. There is a high degree of individual variability in menstrual pain severity, the number of painful sites, and co-occurring gastrointestinal symptoms. Distinct dysmenorrhea symptom-based phenotypes were previously identified, but the biological underpinnings of these phenotypes are less known. One underexplored contributor is the vaginal microbiome. The vaginal microbiota differs significantly among reproductive-age women and may modulate as well as amplify reproductive tract inflammation, which may contribute to dysmenorrhea symptoms. OBJECTIVES: The objective of this study was to examine associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome compositions on- and off-menses. METHODS: We conducted a prospective, longitudinal, pilot study of 20 women (aged 15-24 years) grouped into three dysmenorrhea symptom-based phenotypes: "mild localized pain," "severe localized pain," and "severe multiple pain and gastrointestinal symptoms." Over one menstrual cycle, participants provided vaginal swabs when they were on- and off-menses. We assayed the vaginal microbiome using 16S rRNA gene sequencing. Permutational multivariate analysis of variance tests were used to compare microbiome compositions across phenotypes, with heat maps generated to visualize the relative abundance of bacterial taxa. RESULTS: The vaginal microbiome compositions (n = 40) were different across the three phenotypes. After separating the on-menses (n = 20) and off-menses (n = 20) specimens, the statistically significant difference was seen on-menses, but not off-menses. Compared to the "mild localized pain" phenotype, participants in the "multiple severe symptoms" phenotype had a lower lactobacilli level and a higher abundance of Prevotella, Atopobium, and Gardnerella when on-menses. We also observed trends of differences across phenotypes in vaginal microbiome change from off- to on-menses. DISCUSSION: The study provides proof-of-concept data to support larger studies on associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome that might lead to new intervention targets and/or biomarkers for dysmenorrhea. This line of research has the potential to inform precision dysmenorrhea treatment that can improve women's quality of life.Item Characterization of the virome associated with Haemagogus mosquitoes in Trinidad, West Indies(Springer Nature, 2021-08-16) Ali, Renee; Jayaraj, Jayaraman; Mohammed, Azad; Chinnaraja, Chinnadurai; Carrington, Christine V.F.; Severson, David W.; Ramsubhag, Adesh; Medical and Molecular Genetics, School of MedicineCurrently, there are increasing concerns about the possibility of a new epidemic due to emerging reports of Mayaro virus (MAYV) fever outbreaks in areas of South and Central America. Haemagogus mosquitoes, the primary sylvan vectors of MAYV are poorly characterized and a better understanding of the mosquito's viral transmission dynamics and interactions with MAYV and other microorganisms would be important in devising effective control strategies. In this study, a metatranscriptomic based approach was utilized to determine the prevalence of RNA viruses in field-caught mosquitoes morphologically identified as Haemagogus janthinomys from twelve (12) forest locations in Trinidad, West Indies. Known insect specific viruses including the Phasi Charoen-like and Humaiata-Tubiacanga virus dominated the virome of the mosquitoes throughout sampling locations while other viruses such as the avian leukosis virus, MAYV and several unclassified viruses had a narrower distribution. Additionally, assembled contigs from the Ecclesville location suggests the presence of a unique uncharacterized picorna-like virus. Mapping of RNA sequencing reads to reference mitochondrial sequences of potential feeding host animals showed hits against avian and rodent sequences, which putatively adds to the growing body of evidence of a potentially wide feeding host-range for the Haemagogus mosquito vector.Item Exploration of the integration of microbiology and immunology emerging topics into undergraduate medical education(Taylor & Francis, 2024) Bauer, Margaret E.; Akbar, Samina; Bauler, Timothy J.; Chacon, Jessica; McClelland, Erin E.; Staudaher, Shawn; Zhao, Yuan; Microbiology and Immunology, School of MedicinePurpose: Medical school educators face challenges determining which new and emerging topics to incorporate into medical school curricula, and how to do so. A study was conducted to gain a better understanding of the integration of emerging topics related to microbiology and immunology in the undergraduate medical curriculum (UME). Methods: An anonymous survey with 17 questions was emailed to medical school faculty who teach immunology and/or microbiology through the DR-Ed listserv, the American Society for Microbiology (ASM) Connect listserv, and attendees of the Association of Medical School Microbiology and Immunology Chairs (AMSMIC) Educational Strategies Workshop. Participants were asked about experiences, perceptions, and the decision-making process regarding integrating emerging topics into UME. Results: The top emerging topics that were added to the curriculum or considered for addition in the last 10 years included COVID-19, Zika virus, mRNA vaccines, and Mpox (formerly known as monkeypox). Most respondents reported lectures and active learning as the major methods for topic delivery, with most faculty indicating that formative assessment was the best way to assess emerging topics. Content experts and course directors were the most cited individuals making these decisions. Top reasons for incorporating emerging topics into curricula included preparing students for clinical treatment of cases, followed by demonstrating the importance of basic science, and opportunities to integrate basic science into other disciplines. Challenges for incorporating these topics included making room in an already crowded curriculum, followed by content overload for students. Conclusions: This study describes the rationale for integrating emerging topics related to microbiology and immunology into UME, and identifies the current new and emerging topics, as well as the main methods of integration and assessment. These results may be used by medical educators to inform curricular decisions at their institutions. Future studies will include developing innovative learning modules that overcome barriers to integration.Item Exploring the Bacterial Diversity of the Male Urethra During Idiopathic Urethritis(2020-08) Farrell, Rowan Micah; Nelson, David E.; Bauer, Margaret; Spinola, StanleyIdiopathic urethritis (IU) comprises up to 50% of symptomatic cases of male urethritis in clinical settings. The syndrome is of an unknown etiology but may be due to an as yet unidentified bacterial pathogen(s). We were interested in identifying pathogens that could cause IU using multiple methods. Shotgun metagenomic sequencing or 16S rRNA sequencing methods can provide rich datasets but are limited by the completeness of the corresponding sequence reference databases. We generated metagenomic and 16S datasets from DNA extracted from urethral swabs of men with IU to determine the composition of their urethral microbiome. In order to enrich the corresponding reference databases used to identify the reads in the sequence datasets, I cultivated bacteria from the first void urine (FVU) of men with IU. My goal was to grow and whole genome sequence bacterial isolates that are not currently represented in the reference databases. Of the 216 men we enrolled at the Bell Flower STD clinic in Indianapolis, IN, 59 men had IU. I grew a total of 802 isolates from the FVU of the IU patients and identified those isolates using colony-based 16S rRNA PCR. Based on % sequence similarity to the nearest type strain, I sorted the 16S alleles into four categories: Species (≥98 % identity) (N=264), Genus (≥95 % identity) (N=407), Closest Match (<95 % identity) (N=95), and No Hit (0 % identity) (N=22). There were 24 genera represented in the isolate collection. Of these, the six most abundant genera were Streptococcus, Staphylococcus, Corynebacterium, Haemophilus, Gardnerella, and Prevotella. These six genera composed nearly 80% of all IU-associated isolates. All sequences below 98% sequence similarity represent potentially novel strains of bacteria. We will proceed with whole genome sequencing of bacterial isolates with the goal of improving genome database coverage of bacterial diversity in the male urethra.Item Filamentous bacteriophage delays healing of Pseudomonas-infected wounds(Elsevier, 2022) Bach, Michelle S.; de Vries, Christiaan R.; Khosravi, Arya; Sweere, Johanna M.; Popescu, Medeea C.; Chen, Qingquan; Demirdjian, Sally; Hargil, Aviv; Van Belleghem, Jonas D.; Kaber, Gernot; Hajfathalian, Maryam; Burgener, Elizabeth B.; Liu, Dan; Tran, Quynh-Lam; Dharmaraj, Tejas; Birukova, Maria; Sunkari, Vivekananda; Balaji, Swathi; Ghosh, Nandini; Mathew-Steiner, Shomita S.; El Masry, Mohamed S.; Keswani, Sundeep G.; Banaei, Niaz; Nedelec, Laurence; Sen, Chandan K.; Chandra, Venita; Secor, Patrick R.; Suh, Gina A.; Bollyky, Paul L.; Surgery, School of MedicineChronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.Item Flesh-eating bacteria infections are on the rise in the US − a microbiologist explains how to protect yourself(The Conversation US, Inc., 2023-09-25) Sullivan, BillItem Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells(eLife Sciences, 2023-03-02) Ke, Fang; Benet, Zachary L.; Maz, Mitra P.; Liu, Jianhua; Dent, Alexander L.; Kahlenberg, Joanne Michelle; Grigorova, Irina L.; Microbiology and Immunology, School of MedicineFollicular regulatory T cells (Tfr) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfr can directly repress germinal center (GC) B cells that acquire autoantigens is unclear. Moreover, TCR specificity of Tfr to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfr. Targeting of these proteins to antigen-specific B cells in mice triggers rapid accumulation of Tfr with immunosuppressive characteristics. Tfr then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response.Item Guns, not roses – here’s the true story of penicillin’s first patient(The Conversation US, Inc., 2022-03-11) Sullivan, BIllItem High frequency of viridians group streptococci bacteremia in pediatric neuroblastoma high-risk patients during induction chemotherapy(Springer Nature, 2023-04-06) El Kebbi, Ola; Prather, Cassandra S.; Elmuti, Lena; Khalifeh, Malak; Alali, Muayad; Pediatrics, School of MedicineExisting literature on febrile neutropenia (FN) has categorized patients with acute leukemia or those undergoing allogeneic stem cell transplantation (SCT) as being high risk for severe infection, bacteremia, and poor outcomes. Comprehensive studies of infection risk in pediatric high-risk neuroblastoma (NB-HR) during induction chemotherapy are limited, and mostly merged within the solid tumor (ST) group. Therefore, it is unclear whether infectious complications and outcomes for NB-HR are the same as in other ST groups. We conducted a retrospective medical record review of pediatric FN patients in a single center from March 2009 to December 2016. FN episodes were categorized into five groups based on underlying diagnosis (acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), NB-HR during induction chemotherapy, other solid tumors, and SCT). Comparative analyses of infectious complications between patients with NB-HR and those with other types of cancer diagnoses were performed. A total of 667 FN episodes (FNEs) were identified in 230 patients. FNEs occurred in 82 episodes with NB-HR. Bloodstream infection (BSI) occurred in 145 (21.7%) of total FN episodes. The most isolated organisms were the viridians group streptococci (VGS) (25%). NB-HR patients have higher rates of VGS bacteremia (OR 0.15, 95% [CI 0.04, 0.56]) and are more likely to be admitted to the Pediatric Intensive Care Unit (PICU) compared to patients with other solid tumors (OR 0.36, 95% [CI 0.15, 0.84]). Interestingly, there is no difference in VGS rates between patients with NB-HR and those with AML despite the fact that NB-HR patients do not receive a cytosine arabinoside (AraC)-based regimen. This large neuroblastoma cohort showed that patients with NB-HR during induction chemotherapy are at higher risk for VGS bacteremia and PICU admissions compared with patients with other solid tumors. Further prospective studies are needed to investigate infection-related complications in this high-risk group and to improve morbidity and mortality.