In the United States in 2021, an outbreak of 4 cases of Burkholderia pseudomallei, the etiologic agent of melioidosis and a Tier One Select Agent (potential for deliberate misuse and subsequent harm), resulted in 2 deaths. The causative strain, B. pseudomallei ATS2021, was unintentionally imported into the United States in an aromatherapy spray manufactured in India.
View Article and Find Full Text PDFTwo clinically important subspecies, subsp. (type A) and subsp. (type B) are responsible for most tularaemia cases, but these isolates typically form a weak biofilm under conditions.
View Article and Find Full Text PDFis 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.
View Article and Find Full Text PDFPeptidoglycan, found within the cell wall of bacteria, is a structure critical for maintaining cell morphology and providing a protective barrier in diverse environments. Peptidoglycan is a remarkably dynamic structure that is constantly remodeled during cell growth and division by various peptidoglycan enzymes. Numerous peptidoglycan enzymes have been characterized from diverse bacteria and are highly sought after as targets for therapeutics.
View Article and Find Full Text PDFThe notoriety of high-consequence human pathogens has increased in recent years and, rightfully, research efforts have focused on understanding host-pathogen interactions. has been detected in an impressively broad range of vertebrate hosts as well as numerous arthropod vectors and single-celled organisms. Two clinically important subspecies, subsp.
View Article and Find Full Text PDFFront Cell Infect Microbiol
April 2022
Biofilms have been established as an important lifestyle for bacteria in nature as these structured communities often enable survivability and persistence in a multitude of environments. is a facultative intracellular Gram-negative bacterium found throughout much of the northern hemisphere. However, biofilm formation remains understudied and poorly understood in as non-substantial biofilms are typically observed by the clinically relevant subspecies subsp.
View Article and Find Full Text PDFPlague, caused by the bacterial pathogen , is a vector-borne disease that has caused millions of human deaths over several centuries. Presently, human plague infections continue throughout the world. Transmission from one host to another relies mainly on infected flea bites, which can cause enlarged lymph nodes called buboes, followed by septicemic dissemination of the pathogen.
View Article and Find Full Text PDFRelatively recent advances in plague vaccinology have produced the recombinant fusion protein F1-V plague vaccine. This vaccine has been shown to readily protect mice from both bubonic and pneumonic plague. The protection afforded by this vaccine is solely based upon the immune response elicited by the F1 or V epitopes expressed on the F1-V fusion protein.
View Article and Find Full Text PDFis one of several biothreat agents for which a licensed vaccine is needed to protect against this pathogen. To aid in the development of a vaccine protective against pneumonic tularemia, we generated and characterized a panel of isolates that can be used as challenge strains to assess vaccine efficacy. Our panel consists of both historical and contemporary isolates derived from clinical and environmental sources, including human, tick, and rabbit isolates.
View Article and Find Full Text PDFArabinose 5-phosphate isomerase (API) catalyzes the reversible isomerization of Ribulose 5-phosphate (Ru5P) to Arabinose 5-Phosphate (Ar5P) for the production of 3-deoxy-2-octulosonic acid 8-phosphate (KDO), a component of bacterial lipopolysaccharide (LPS) of gram-negative bacteria. API is an attractive target for therapeutic development against gram-negative bacterial pathogens. The current assay method of API activity utilizes a general reaction for keto sugar determination in a secondary, 3-h color development reaction with 25 N sulfuric acid which poses hazard to both personnel and instrumentation.
View Article and Find Full Text PDFThe etiologic agent of plague, , is a globally distributed pathogen which poses both a natural and adversarial threat. Due largely to the rapid course and high mortality of pneumonic plague, vaccines are greatly needed. Two-component protein vaccines have been unreliable and potentially vulnerable to vaccine resistance.
View Article and Find Full Text PDFFailure of an existing effluent decontamination system (EDS) prompted the consideration of commercial off-the-shelf solutions for decontamination of containment laboratory waste. A bleach-based chemical EDS was purchased to serve as an interim solution. Studies were conducted in the laboratory to validate inactivation of spores with bleach in complex matrices containing organic simulants including fetal bovine serum, humic acid, and animal room sanitation effluent.
View Article and Find Full Text PDFLow molecular mass penicillin binding proteins (LMM PBP) are bacterial enzymes involved in the final steps of peptidoglycan biosynthesis. In Escherichia coli, most LMM PBP exhibit dd-carboxypeptidase activity, are not essential for growth in routine laboratory media, and contributions to virulent phenotypes remain largely unknown. The Francisella tularensis Schu S4 genome harbors the dacD gene (FTT_1029), which encodes a LMM PBP with homology to PBP6b of E.
View Article and Find Full Text PDFis the causative agent of tularemia and has gained recent interest as it poses a significant biothreat risk. is commonly used as a laboratory surrogate for tularemia research due to genetic similarity and susceptibility of mice to infection. Currently, there is no FDA-approved tularemia vaccine, and identifying therapeutic targets remains a critical gap in strategies for combating this pathogen.
View Article and Find Full Text PDFFor safety, designated Select Agents in tissues must be inactivated and viability tested before the tissue undergoes further processing and analysis. In response to the shipping of samples of "inactivated" Bacillus anthracis that inadvertently contained live spores to nonregulated entities and partners worldwide, the Federal Register now mandates in-house validation of inactivation procedures and standardization of viability testing to detect live organisms in samples containing Select Agents that have undergone an inactivation process. We tested and validated formaldehyde and glutaraldehyde inactivation procedures for animal tissues infected with virulent B.
View Article and Find Full Text PDFMouse models have been essential to generate supporting data for the research of infectious diseases. Burkholderia pseudomallei, the etiological agent of melioidosis, has been studied using mouse models to investigate pathogenesis and efficacy of novel medical countermeasures to include both vaccines and therapeutics. Previous characterization of mouse models of melioidosis have demonstrated that BALB/c mice present with an acute infection, whereas C57BL/6 mice have shown a tendency to be more resistant to infection and may model chronic disease.
View Article and Find Full Text PDFIn 2015, a laboratory of the United States Department of Defense (DoD) inadvertently shipped preparations of gamma-irradiated spores of that contained live spores. In response, a systematic evidence-based method for preparing, concentrating, irradiating, and verifying the inactivation of spore materials was developed. We demonstrate the consistency of spore preparations across multiple biological replicates and show that two different DoD institutions independently obtained comparable dose-inactivation curves for a monodisperse suspension of spores containing 3 × 10 CFU.
View Article and Find Full Text PDFBurkholderia pseudomallei (Bp), the agent of melioidosis, causes disease ranging from acute and rapidly fatal to protracted and chronic. Bp is highly infectious by aerosol, can cause severe disease with nonspecific symptoms, and is naturally resistant to multiple antibiotics. However, no vaccine exists.
View Article and Find Full Text PDFBurkholderia mallei (Bm) is a highly infectious intracellular pathogen classified as a category B biological agent by the Centers for Disease Control and Prevention. After respiratory exposure, Bm establishes itself within host macrophages before spreading into major organ systems, which can lead to chronic infection, sepsis, and death. Previously, we combined computational prediction of host-pathogen interactions with yeast two-hybrid experiments and identified novel virulence factor genes in Bm, including BMAA0553, BMAA0728 (tssN), and BMAA1865.
View Article and Find Full Text PDFIn some Bacillus species, including Bacillus subtilis, the coat is the outermost layer of the spore. In others, such as the Bacillus cereus family, there is an additional layer that envelops the coat, called the exosporium. In the case of Bacillus anthracis, a series of fine hair-like projections, also referred to as a "hairy" nap, extends from the exosporium basal layer.
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