Article
Immunology
Lydia M. Roberts, Tara D. Wehrly, Ian Leighton, Patrick Hanley, Jamie Lovaglio, Brian J. Smith, Catharine M. Bosio
Summary: Pulmonary infections trigger tissue-resident and circulating T cell responses, which are crucial for vaccine development. The relative contribution of tissue-resident and circulating T cells in Francisella tularensis infection is not fully understood, hindering the design of effective vaccines. This study elucidates the role of circulating T cells in host defense using a parabiotic mouse model.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Mengsu Zhao, Yanfang Zhai, Xiaodong Zai, Yunyun Mao, Enbo Hu, Zhaodong Wei, Yan Li, Kai Li, Yanhong Liu, Junjie Xu, Rui Yu, Wei Chen
Summary: No FDA-approved vaccines are available for tularemia, a highly contagious disease caused by Francisella tularensis. This study identified potential protective antigens for vaccine development, including Tul4, OmpA, FopA, and DnaK, and found that using an adenovirus vector encoding these proteins can induce protective immunity against Ft infection. Intramuscular vaccination with Ad5-Tul4 effectively eliminated Ft colonization in multiple organs and provided high levels of protection, while intranasal vaccination only protected against intranasal challenge.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Mateja Ozanic, Valentina Marecic, Masa Knezevic, Ina Kelava, Pavla Stojkova, Lena Lindgren, Jeanette E. Broms, Anders Sjostedt, Yousef Abu Kwaik, Marina Santic
Summary: Francisella tularensis is a highly pathogenic bacterium that causes tularemia. The bacterium encodes a type 4 pili (T4P) system, which is important for adherence to host cells, protein secretion, and virulence. The PilO protein plays an essential role in pilus assembly, adherence to human macrophages, effector protein secretion, and intracellular replication. A pilO mutant is attenuated for virulence in mice and shows impaired phagosomal escape and replication in lung, liver, and spleen.
Article
Microbiology
Brandi E. Hobbs, Courtney A. Matson, Vasileios Theofilou, Tonya J. Webb, Rania H. Younis, Eileen M. Barry
Summary: The FptA and FptF proteins of Ft are crucial for pathogenesis and modulation of host immune response, and LVS Delta fptA and LVS Delta fptF vaccine strains are highly attenuated and provide effective protection against lethal challenge.
Article
Biotechnology & Applied Microbiology
Kevin D. Mlynek, Curtis R. Cline, Sergei S. Biryukov, Ronald G. Toothman, Beth A. Bachert, Christopher P. Klimko, Jennifer L. Shoe, Melissa Hunter, Zander M. Hedrick, Jennifer L. Dankmeyer, Sherry Mou, David P. Fetterer, Ju Qiu, Eric D. Lee, Christopher K. Cote, Qingmei Jia, Marcus A. Horwitz, Joel A. Bozue
Summary: The study found that the potential tularemia vaccine candidate rLVS Delta capB/iglABC can provide robust protection against different strains of Francisella tularensis. In animal experiments, rats vaccinated with rLVS showed high levels of protection against various F. tularensis strains.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2023)
Article
Microbiology
Sara Doina Schutz, Nicole Liechti, Ekkehardt Altpeter, Anton Labutin, Tsering Wutrich, Kristina Maria Schmidt, Michael Buettcher, Michel Moser, Remy Bruggmann, Matthias Wittwer
Summary: This study aims to characterize the genetic diversity of Francisella tularensis subsp. holarctica (Fth) in Switzerland and describe the phylogeographic relationship of isolates using single nucleotide polymorphism (SNP) analysis. The findings provide insight into the epidemiology of tularemia in Switzerland by combining human surveillance data, antimicrobial resistance tests, and whole genome sequencing. The results show that the Fth population in Switzerland belongs to major clade B.6, specifically subclades B.45 and B.46, with no resistance to clinically recommended antibiotics.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Lara R. Mittereder, Jonathan Swoboda, Roberto De Pascalis, Karen L. Elkins
Summary: IL-12p40 is important for the clearance of F. tularensis Live Vaccine Strain (LVS) and its role is independent of its functions as a part of the heterodimeric cytokines IL-12p70 or IL-23. The absence of IL-12p40 in infected mice leads to the development of a chronic and unresolved infection. The study also investigates potential mechanisms for IL-12p40 in F. tularensis clearance.
Review
Microbiology
McKayla J. Nicol, David R. Williamson, David E. Place, Girish S. Kirimanjeswara
Summary: Francisella tularensis is the etiological agent of tularemia, with different routes of infection leading to variable clinical presentations and mortality rates. Understanding the immune correlates of protection against infection by disparate routes is crucial for clinical management, treatment, and vaccine development.
Article
Immunology
Patrik D'haeseleer, Nicole M. Collette, Victoria Lao, Brent W. Segelke, Steven S. Branda, Magdalena Franco
Summary: Peptide-based subunit vaccines offer safety and cost-effective production, with linear epitopes having advantages of simple structure, ease of synthesis, and immune response stimulation, but lower accuracy in prediction, necessitating experimental verification.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Beth A. Bachert, Joshua B. Richardson, Kevin D. Mlynek, Christopher P. Klimko, Ronald G. Toothman, David P. Fetterer, Andrea E. Luquette, Kitty Chase, Jessica L. Storrs, Ashley K. Rogers, Christopher K. Cote, David A. Rozak, Joel A. Bozue
Summary: Researchers have characterized a panel of virulent F. tularensis strains for vaccine testing, finding high genomic similarity but also unique mutations and unexpected diversity within some strains. These findings indicate the effectiveness of the strains as challenge strains for future vaccine development efforts.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Ritu Gaur, Dipesh Kumar Verma, Syed Imteyaz Alam, Dev Vrat Kamboj
Summary: Tularemia, caused by Francisella tularensis, is a widespread zoonotic disease without an approved vaccine. This study successfully identified ten MHC class I-restricted peptides from Francisella, with the top three peptides showing high binding affinity with MHC class I molecules through in silico docking studies, suggesting their potential as vaccine candidates for human studies.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Cell Biology
Lydia M. Roberts, Ian Leighton, Benjamin Schwarz, Tara D. Wehrly, Tyler J. Evans, Catharine M. Bosio
Summary: The metabolite itaconate plays a critical role in modulating inflammatory responses among macrophages infected with intracellular pathogens. This study investigates its effect on T cell responses using Francisella tularensis as a model. It reveals that itaconate deficient mice have prolonged primary infection but are more resistant to secondary infection, suggesting the importance of metabolic perturbations in antigen presenting cells on vaccine-elicited immune responses.
CELLULAR IMMUNOLOGY
(2022)
Article
Microbiology
Zhuo Ma, Matthew Higgs, Maha Alqahtani, Chandra Shekhar Bakshi, Meenakshi Malik
Summary: This study reveals the important role of thioredoxin TrxA1 in the oxidative stress response of Francisella tularensis and its regulation of the master regulator oxyR. TrxA1 is also essential for the intracellular survival and growth of Francisella. These findings provide novel insights into the oxidative stress defense mechanisms of Francisella tularensis.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Chemistry, Medicinal
Heer H. Mehta, Xinhao Song, Yousif Shamoo
Summary: In vitro experimental evolution is a valuable tool to identify genetic changes responsible for antimicrobial resistance. However, the in vivo context contributes to the success of evolutionary trajectories, particularly in intracellular niches. This study conducted ex vivo evolution to identify antibiotic resistance in Francisella tularensis subsp. holarctica within macrophages, and found differences in mutational profiles between different environments. The results demonstrate the significance of host mediated stress during resistance evolution.
ACS INFECTIOUS DISEASES
(2023)
Article
Immunology
Maha Alqahtani, Zhuo Ma, Kayla Fantone, Meenakshi Malik, Chandra Shekhar Bakshi
Summary: This study found that both AIM2 and NLRP3 are dispensable for vaccination-induced immunity against respiratory tularemia caused by F. tularensis, as even deficient mice were fully protected against lethal challenge doses of the bacteria and displayed unaffected production of antibody and cell-mediated responses.
INFECTION AND IMMUNITY
(2021)
Article
Immunology
D. Califano, Y. Furuya, S. Roberts, D. Avram, A. N. J. McKenzie, D. W. Metzger
MUCOSAL IMMUNOLOGY
(2018)
Article
Immunology
Donald J. Steiner, Yoichi Furuya, Dennis W. Metzger
INFECTION AND IMMUNITY
(2018)
Article
Microbiology
Tiffany M. Zarrella, Dennis W. Metzger, Guangchun Bai
JOURNAL OF BACTERIOLOGY
(2018)
Article
Immunology
Danielle Califano, Yoichi Furuya, Dennis W. Metzger
JOURNAL OF IMMUNOLOGY
(2018)
Article
Immunology
Sean Roberts, Dennis W. Metzger, Steven M. Szczepanek
Article
Immunology
Sean Roberts, Clare M. Williams, Sharon L. Salmon, Jesse L. Bonin, Dennis W. Metzger, Yoichi Furuya
Article
Microbiology
Tarani Kanta Barman, Rachael Racine, Jesse L. Bonin, Danielle Califano, Sharon L. Salmon, Dennis W. Metzger
Summary: Bacterial co-infections are a common and challenging clinical complication of influenza. This study found that mice lacking both type-I and type-II interferon (IFN) pathways demonstrated minimal lung pathology and increased survival in a pneumococcal-influenza virus superinfection model. Therapeutic neutralization of both type-I and type-II IFN pathways provided optimal protection to superinfected wild-type mice.
Article
Virology
Amit K. Singh, Kathleen A. Stellrecht, Thilaka Arunachalam, Tarani K. Barman, Michael D. Robek, Michael J. Waxman, Sarah L. Elmendorf, Dennis W. Metzger
Summary: This study found active SARS-CoV-2 virus in only a small percentage of samples from congregate care patients, primarily in those with high viral loads/low antibody titers and early in the disease progression.
JOURNAL OF CLINICAL VIROLOGY
(2021)
Review
Virology
Tarani Kanta Barman, Dennis W. Metzger
Summary: This review discusses the role of disease tolerance in viral-bacterial co-infection, focusing on host cytokines and cells that promote tissue protection and damage control.
Article
Multidisciplinary Sciences
Tarani Kanta Barman, Victor C. Huber, Jesse L. Bonin, Danielle Califano, Sharon L. Salmon, Andrew N. J. McKenzie, Dennis W. Metzger
Summary: This study reveals the interplay between host interferon (IFN)-gamma and viral PB1-F2 virulence protein in regulating the functions of innate lymphoid cells (ILCs) and T cells during influenza virus infection. In the absence of IFN-gamma, lung ILC2s initiate a robust IL-5 response, leading to improved tissue integrity and increased survival. However, the presence of functional PB1-F2 suppresses ILC2 responses and induces a dominant IL-13 CD8 T cell response. This study also demonstrates the importance of IFN-gamma in host resistance against lethal doses of the influenza virus.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Tarani Kanta Barman, Amit K. Singh, Jesse L. Bonin, Tanvir Noor Nafiz, Sharon L. Salmon, Dennis W. Metzger
Summary: This study found that coinfection of SARS-CoV-2 and Streptococcus pneumoniae leads to lung inflammation and death, and the treatment methods differ. Treatment with murine GM-CSF can reduce bacteria and pathology, partially protecting from death, but therapeutic targeting of IFNs does not work. Combined vaccination provides 100% protection against subsequent coinfection.
Article
Respiratory System
Cedric Vonarburg, Marius Loetscher, Martin O. Spycher, Alain Kropf, Marlies Illi, Sharon Salmon, Sean Roberts, Karin Steinfuehrer, Ian Campbell, Sandra Koernig, Joseph Bain, Monika Edler, Ulrich Baumann, Sylvia Miescher, Dennis W. Metzger, Alexander Schaub, Fabian Kasermann, Adrian W. Zuercher
RESPIRATORY RESEARCH
(2019)
Article
Immunology
Donald J. Steiner, Yoichi Furuya, Michael B. Jordan, Dennis W. Metzger
INFECTION AND IMMUNITY
(2017)