Francisella tularensis is a Gram-negative, facultative intracellular pathogen and the causative agent of a lethal human disease known as tularemia. Due to its extremely high virulence and potential to be used as a bioterror agent, F. tularensis is classified by the CDC as a Category A Select Agent. As an intracellular pathogen, F. tularensis during its intracellular residence encounters a number of oxidative and nitrosative stresses. The roles of the primary antioxidant enzymes SodB, SodC and KatG in oxidative stress resistance and virulence of F. tularensis live vaccine strain (LVS) have been characterized in previous studies. However, very fragmentary information is available regarding the role of peroxiredoxin of the AhpC/TSA family (annotated as AhpC) of F. tularensis SchuS4; whereas the role of AhpC of F. tularensis LVS in tularemia pathogenesis is not known. This study was undertaken to exhaustively investigate the role of AhpC in oxidative stress resistance of F. tularensis LVS and SchuS4. We report that AhpC of F. tularensis LVS confers resistance against a wide range of reactive oxygen and nitrogen species, and serves as a virulence factor. In highly virulent F. tularensis SchuS4 strain, AhpC serves as a key antioxidant enzyme and contributes to its robust oxidative and nitrosative stress resistance, and intramacrophage survival. We also demonstrate that there is functional redundancy among primary antioxidant enzymes AhpC, SodC, and KatG of F. tularensis SchuS4. Collectively, this study highlights the differences in antioxidant defense mechanisms of F. tularensis LVS and SchuS4.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213699 | PLOS |
Angew Chem Int Ed Engl
October 2024
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476, Potsdam, Germany.
Microbiol Spectr
August 2024
Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Unlabelled: Traditionally, successful vaccines rely on specific adaptive immunity by activating lymphocytes with an attenuated pathogen, or pathogen subunit, to elicit heightened responses upon subsequent exposures. However, recent work with and other pathogens has identified a role for "trained" monocytes in protection through memory-like but non-specific immunity. Here, we used an co-culture approach to study the potential role of trained macrophages, including lung alveolar macrophages, in immune responses to the Live Vaccine Strain (LVS) of is an intracellular bacterium that replicates within mammalian macrophages and causes respiratory as well as systemic disease.
View Article and Find Full Text PDFFront Microbiol
April 2024
Department of Biomedical Sciences, West Liberty University, West Liberty, WV, United States.
[This corrects the article DOI: 10.3389/fmicb.2024.
View Article and Find Full Text PDFFront Microbiol
February 2024
Department of Biomedical Sciences, West Liberty University, West Liberty, WV, United States.
is a gram-negative, intracellular pathogen which can cause serious, potentially fatal, illness in humans. Species of are found across the Northern Hemisphere and can infect a broad range of host species, including humans. Factors affecting the persistence of in the environment and its epidemiology are not well understood, however, the ability of to enter a viable but non-culturable state (VBNC) may be important.
View Article and Find Full Text PDFHum Vaccin Immunother
December 2023
Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.
is one of the several biothreat agents for which a licensed vaccine is needed. To ensure vaccine protection is achieved across a range of virulent strains, we assembled and characterized a panel of isolates to be utilized as challenge strains. A promising tularemia vaccine candidate is rLVS Δ/ (rLVS), in which the vector is the LVS strain with a deletion in the gene and which additionally expresses a fusion protein comprising immunodominant epitopes of proteins IglA, IglB, and IglC.
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