Distinguished Speaker Seminar Series in Infectious Diseases
Bryan Hsu and Clayton Caswell
The Center for Emerging, Zoonotic and Arthropod-borne Pathogens (CeZAP) introduces the CeZAP Distinguished Speaker Seminar Series in Infectious Diseases. This university wide seminar series at Virginia Tech invites outstanding scientists nationally to give presentations to CeZAP and broader university community on topics of current interest in the broad area of infectious diseases. Diversity of seminar topics is essential to meeting the purpose of the Distinguished Speaker Seminar Series in Infectious Diseases. Each spring, nominations for nationally distinguished speakers for the seminar series for the following academic year will be solicited from CeZAP affiliated faculty. The seminar coordinators (Drs. Jonathan Auguste and Bryan Hsu) will coordinate the selection of speakers, and the CeZAP faculty nominators will serve as the host for the national speakers. We expect to host at least one nationally distinguished speaker each month, and the remaining speakers will feature our own CeZAP affiliated faculty.
FALL 2023 SCHEDULE
Seminar Date & Time:
Thursdays at 12:30 - 1:30 pm
In person in LS 1 Conference Room 101
(Note: this is a new location from our previous seminars). Virtual seminars will be indicated below.
August 24, 2023
Rogerio Bataglioli, Ph.D. Postdoc, Hsu Lab
"Developing a prophylactic approach to preventing Salmonella Typhimurium infection by the rational design of phage-bacterial interactions"
Host: Bryan Hsu
Salmonella enterica serovar Typhimurim is a notorious diarrheal pathogen and is a contributor to the emergence and spread of antibiotic-resistant clinical isolates. Bacteriophages (phages) are bacterial viruses that have received renewed interest as antimicrobial agents. One limitation to this application of phages (“Phage Therapy”) is that phages must be administered after the establishment of infection and the quantity of dosed phage is substantially lower than that of the established pathogen. We hypothesize that establishing a sustained basal concentration of anti-pathogen phage in the gut will provide protection against invading pathogens. To test this, we genetically engineer the commensal gut bacteria, Escherichia coli, to carry a virulent mutant of a S. Typhimurium phage, P22, as a prophage by providing the lysogenic machinery in trans. We find that a virulent phage P22 phage produced from E. coli is better at killing S. Typhimurium in vitro than P22 or E. coli alone. Our work represents an alternative approach to applying phage therapy in the gut: as prophylactic protection instead of remedial treatment.
August 31, 2023
T.M. Murali, Ph.D. Professor & Associate Department Head of Research, Department of Computer Science, COE
"Pandemic Prediction and Prevention: A Destination Areas Project"
The Pandemic Prediction and Prevention Destination Areas (PPP DA) project has an aspirational vision: a world where we accurately foresee pandemics and proactively minimize their impact. The PPP DA includes faculty, scientists, graduate, and undergraduate students from eight colleges at Virginia Tech working in collaboration with leading researchers at other universities and partners. Our mission is to forecast and control future viral pandemics by addressing the grand challenge of uncovering the genetic, molecular, cellular, and chemical rules of life underlying virus-host interactions through community-based and ethically grounded research. I will describe our research thrusts, plans for hiring new faculty colleagues, and how the PPP DA aligns with the Beyond Boundaries vision of our institution. I will present our plans to educate and train a new generation of scientists with transformative technical and professional skills to form convergent teams that can protect and empower humans by anticipating future outbreaks and preventing them from becoming pandemics. To conclude, we will have an open discussion on ways in which the PPP DA and CeZAP can work together.
September 7, 2023
Jean Celli, Ph.D. Professor, Department of Microbiology and Molecular Genetics, University of Vermont
“Roles of Brucella Type IV effector proteins in bacterial proliferation”
Host: Clay Caswell, Ph.D.
The bacterial pathogen Brucella abortus uses Type IV secretion-mediated intracellular delivery of effector proteins to promote its infectious cycle and proliferation in phagocytic cells of the infected host. While several Type IV effectors are known to modulate innate immune, cell-intrinsic responses or promote biogenesis of its niche of replication, whether Brucella intracellular growth within its vacuole requires Type IV effector functions has remained unclear. Here I will present recent evidence that B. abortus delivers various effector proteins that specifically contribute to intracellular proliferation by targeting endoplasmic reticulum-associated and endocytic cellular pathways, highlighting global remodeling of host functions during infection.
September 14, 2023:
Helen Blackwell, Ph.D. Norman C. Craig Professor, Department of Chemistry, University of Wisconsin-Madison
"Chemical strategies to intercept and alter bacterial communication pathways"
Host: Ann Stevens, Ph.D.
Our research is broadly focused on the design, synthesis, and application of non-native ligands that can intercept bacterial quorum sensing and provide new insights into its role in host/microbe interactions and the environment. At high cell densities, many common bacteria use quorum sensing to switch from a single cell existence to that of a multicellular community. This lifestyle switch is significant; only in groups will pathogenic bacteria turn on virulence pathways and grow into impervious communities called biofilms that are the bases of chronic biofouling and infections. We have developed a range of non-native analogs of autoinducer signals that can block or activate quorum sensing pathways, some with high selectivities, potencies, and chemical stabilities. These molecules provide a novel approach to study quorum sensing with both spatial and temporal control in a range of settings. We have applied our chemical tools in vitro and in vivo to investigate quorum sensing as an anti-infective target. Ongoing work is focused on understanding their interactions with key protein receptors involved in quorum sensing pathways, with native signals, and with membranes. In this talk, I will introduce my lab’s research approach and highlight our most recent results.
September 21, 2023:
ID IGEP 1st Research Rotation Presentations
September 28, 2023:
Seminar will be held in a different location: Newman Library Multi-Purpose Room (100) and via Zoom
Dr. White’s seminar is part of a broader Human Dimensions of Infectious Diseases research symposium.
Alexandre White, Ph.D., Assistant Professor, Department of Sociology, Johns Hopkins University
"Epidemic Orientalism: Race, Capital, and the Governance of Infectious Disease".
Host: Tom, Ewing, Ph.D.
For most of the 21st century much of the world has taken for granted our ability to fight back pandemics and control them with little effect on day-to-day life. Until the emergence of COVID-19 few in the western world would have had any occasion to consider the histories of infectious disease control that have managed the spread of pandemic threats around the world. Epidemic Orientalism: Race, Capital and the Governance of Infectious Disease tells the story of how epidemic threats become the focus of international management, regulation and control, as well as the political, economic and racial ideologies that have shaped international coordination to stop pandemic spread.
October 5, 2023 – Virtual Seminar
Isabel Gordo, Ph.D.
Title: “Natural Selection in commensal bacteria colonizing the mammalian gut"
Host: Brian Hsu, Ph.D.
More than 100 years ago Élie Metchnikoff wrote that “The dependence of the intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes”. To fulfil Metchnikoff's dream we need to understand the factors that drive change in our gut microbes. In this talk I will focus on intra-host evolution of gut microbes. I will describe the key results that my lab has obtained on how natural selection operates in gut bacteria, as revealed by the methodology of in vivo experimental evolution. These experiments reveal that gut bacteria change evolutionarily at a rapid pace. Such rapid evolution is adaptive and involves either the accumulation of mutations that alter their metabolic preferences or a remarkable fast gain of DNA from other conspecific strains. The later process of horizontal gene transfer is driven by temperate phages, which are bacterial viruses that integrate in bacterial genomes and constitute a substantial component of the gut virome. The data also shows that bacteria colonizing the intestine are able to domesticate their viruses to avoid the cost of their induction while keeping the benefits they may bring.
October 12, 2023:
Stefan Rothenburg, Ph.D. Professor, Dept. Medical Microbiology and Immunology, University of California, Davis
"Poxvirus Evolution and the Molecular Basis for Poxvirus Host Range"
Host: Frank Aylward, Ph.D.
Poxviruses as a group can infect a large number of animals. However, at the level of individual poxvirus species, even closely related poxviruses display highly diverse host ranges and virulence. Because, poxviruses enter host cells by binding to receptors that are highly conserved between different species, their host range is independent of species-specific receptors, and productive infection is largely determined by how well they can antagonize the host immune response. This conflict led to strong selective pressure on both the virus and the host. I will present data highlighting the genetic conflict between the antiviral host protein kinase R (PKR) and poxvirus inhibitors, and discuss consequences of these evolutionary “arms races” for poxvirus host range and virulence. I will also show that poxviruses possess highly adaptable genomes, and present our findings that poxviruses harness host retrotransposons to acquire host genes by horizontal gene transfer.
October 19, 2023:
ID IGEP 2nd Research Rotation Presentations
October 26, 2023:
Jingqiu Liao, Ph.D. Assistant Professor, Department of Civil and Environmental Engineering, COE
"A nationwide investigation of antibiotic resistance genes in soil-dwelling Listeria."
Listeria, including L. monocytogenes, the causative agent of listeriosis in humans, has the genetic machinery to rapidly develop resistance to antibiotics. Indeed, antibiotic resistance among L. monocytogenes isolated from foods and the environment has increased over the past decade, posing a growing threat to food safety and public health. It is believed that environmental changes may select particular antibiotic-resistant clones that can then widely spread in nature. Thus, there is an urgent need to advance our understanding of the ecology and evolution of antibiotic resistance genes (ARGs) in Listeria inhabiting the environment. To this end, we leveraged a nationwide genomic and environmental dataset to characterize ARGs in 596 Listeria isolates detected in soil samples that we collected across the US. We identified five putative functional ARGs (lin, mprF, sul, fosX, and norB) with lin, which confers resistance to lincomycin, being the most prevalent. ARGs were predominantly detected in Listeria sensu stricto species and species more closely related to L. monocytogenes tend to harbor more ARGs. Also, we observed strong evidence of horizontal gene transfer (HGT) across species in all five ARGs and identified potassium, pH, aluminum, forest, zinc, manganese, and iron as the key environmental factors that may influence the ARG acquisition in Listeria. Using machine learning, we showed the richness of ARGs of a given Listeria isolate can be predicted by environmental variables with a mean accuracy of 0.8. Collectively, our data suggest that Listeria may acquire ARGs after speciation through HGT and the acquisition is influenced by environmental factors, chiefly soil properties.
November 2, 2023:
Marshall Bloom, M.D. Chief, Biology of Vector-Borne Viruses Section, NIH
"New dimensions in the study of tick-borne virus infections"
Host: Gillian Eastwood, Ph.D.
November 9, 2023:
Kelly Doran Ph.D. Professor of Immunology & Microbiology, University of Colorado Anschutz School of Medicine
"Life in Mucus: Vaginal Colonization by Group B Streptococcus"
Group B Streptococcus (GBS) asymptomatically colonizes 25-30% of healthy women in the vaginal tract, however it is a risk factor for preterm birth and adverse pregnancy outcomes, and can cause ascending infection in utero or be transmitted to the newborn during birth to cause invasive neonatal disease. GBS colonization is also transient in nature, which likely reflects the contributions of pathogen determinants, interactions with commensal flora, and host factors, making this environment particularly challenging to understand. Though the cervicovaginal mucosa is a natural site for GBS colonization, the specific interactions between GBS and mucins remain unknown. We demonstrate that MUC5B interacts directly with GBS and promotes barrier function by inhibiting both bacterial attachment to human epithelial cells and ascension from the vagina to the uterus in a murine model of GBS colonization. Additionally, using machine learning approaches, we show that vaginal community turnover during GBS colonization is driven by computationally predictable changes in key taxa, including several organisms not previously described in the context of the vaginal microbiota, such as Akkermansia muciniphila, a mucin degrading bacterium. We observed that A. muciniphila experimentally increases GBS vaginal persistence in the mouse and, in a cohort of human vaginal microbiome samples collected throughout pregnancy, we observed an increased prevalence of codetection of GBS and A. muciniphila in patients who delivered preterm compared to those who delivered at full term. These findings reveal the importance and complexity of both the native microbiome and mucins to GBS vaginal persistence.
Host: Bryan Hsu, Ph.D., Clay Caswell, Ph.D.
November 16, 2023:
ID IGEP 3rd Research Rotation Presentations
November 30, 2023:
Aaron Gross Ph.D. Associate Professor, Department of Entomology, CALS
"The Insect Cholinergic System: Challenges and Opportunities in Vector Management"
Insecticides reduce vector populations alleviating the deleterious impacts that arthropods have on public and animal health. Most of the vector control insecticides are repurposed from agriculture, where widespread and overuse expedites the development of resistance. Because of this, there is an urgent need to understand molecular mechanisms of resistance, but to also find new molecules that work at novel or underutilized targets. In insects, acetylcholine functions as the primary excitatory neurotransmitter within the central nervous system (CNS). The insect cholinergic system has been a successful target for insecticides with the development of acetylcholinesterase inhibitors (e.g., organophosphates and carbamates) and modulators of nicotinic acetylcholine receptors (e.g., neonicotinoids, sulfoximines, mesoionics, etc.). However, muscarinic acetylcholine receptors (mAChRs) have not garnered as much attention. Using insect vectors (mosquitoes) and the genetic model organism Drosophila melanogaster, we are understanding the role of the cholinergic system in insecticide resistance. Further, we are exploring the muscarinic system as a target for insect/mosquito control and the disruption of the host-vector interaction. Overall, we propose that the insect muscarinic system could be a valuable target to control vector-borne diseases.