Implementation of a post-exposure tularemia treatment model for pneumonic challenged Fischer rats.

Francisella tularensis is the etiological agent of the potentially fatal disease tularemia. F. tularensis is sensitive to several antibiotic classes; however, the ability to derive antibiotic resistant Francisella strains has been well documented.

Nanolipoprotein particle (NLP) vaccine confers protection against aerosol challenge in a BALB/c mouse model.

Introduction: is the etiological agent of plague, a disease that remains a concern as demonstrated by recent outbreaks in Madagascar. Infection with results in a rapidly progressing illness that can only be successfully treated with antibiotics given shortly after symptom onset. Live attenuated or whole cell inactivated vaccines confer protection against bubonic plague, but pneumonic plague has been more difficult to prevent.

Treatment of bacterial biothreat agents with a novel purified bioactive lactoferrin affects both growth and biofilm formation.

Lactoferrin is known to exhibit broad spectrum activity against a multitude of bacteria, fungi, and viruses due to its multi-functional mode of action. Recently, Lactea Therapeutics and its affiliates have developed a novel, patent-pending technology to purify naturally derived bovine lactoferrin (Lactea Lf) for use as a medical countermeasure that was not previously available. To assess the efficacy of Lactea Lf against biothreat pathogens, we performed biofilm inhibition assays and generated dose-response curves against , , and for proof-of-principle studies.

Virulence of Burkholderia pseudomallei ATS2021 Unintentionally Imported to United States in Aromatherapy Spray.

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.

Mutation of , a -formyltransferase involved in O-antigen synthesis, results in biofilm formation, phase variation and attenuation in .

Two 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.

The rLVS Δ/ vaccine provides potent protection in Fischer rats against inhalational tularemia caused by various virulent strains.

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.

Why vary what's working? Phase variation and biofilm formation in .

The 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.

Phase Variation of LPS and Capsule Is Responsible for Stochastic Biofilm Formation in .

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.

Development, Phenotypic Characterization and Genomic Analysis of a Panel for Tularemia Vaccine Testing.

is 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.

Genetic and Biochemical Analysis of CodY-Mediated Cell Aggregation in Staphylococcus aureus Reveals an Interaction between Extracellular DNA and Polysaccharide in the Extracellular Matrix.

The global regulator CodY links nutrient availability to the regulation of virulence factor gene expression in , including many genes whose products affect biofilm formation. Antithetical phenotypes of both biofilm deficiency and accumulation have been reported for -null mutants; thus, the role of CodY in biofilm development remains unclear. mutant cells of a strain producing a robust biofilm elaborate proaggregation surface-associated features not present on mutant cells that do not produce a robust biofilm.

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues.

Bacterial virulence genes are often regulated at the transcriptional level by multiple factors that respond to different environmental signals. Some factors act directly on virulence genes; others control pathogenesis by adjusting the expression of downstream regulators or the accumulation of signals that affect regulator activity. While regulation has been studied extensively during in vitro growth, relatively little is known about how gene expression is adjusted during infection.

Extracellular polymeric substance (EPS)-degrading enzymes reduce staphylococcal surface attachment and biocide resistance on pig skin in vivo.

Staphylococcal extracellular polymeric substances (EPS) such as extracellular DNA (eDNA) and poly-N-acetylglucosamine surface polysaccharide (PNAG) mediate numerous virulence traits including host colonization and antimicrobial resistance. Previous studies showed that EPS-degrading enzymes increase staphylococcal biocide susceptibility in vitro and in vivo, and decrease virulence in animal models. In the present study we tested the effect of EPS-degrading enzymes on staphylococcal skin colonization and povidone iodine susceptibility using a novel in vivo pig model that enabled us to colonize and treat 96 isolated areas of skin on a single animal in vivo.

Nutritional Regulation of the Sae Two-Component System by CodY in Staphylococcus aureus.

subverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via the exoprotein expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease () gene expression via SaeR/S, but the mechanism remained unknown.

Effects of Low-Dose Amoxicillin on Staphylococcus aureus USA300 Biofilms.

Previous studies showed that sub-MIC levels of β-lactam antibiotics stimulate biofilm formation in most methicillin-resistant Staphylococcus aureus (MRSA) strains. Here, we investigated this process by measuring the effects of sub-MIC amoxicillin on biofilm formation by the epidemic community-associated MRSA strain USA300. We found that sub-MIC amoxicillin increased the ability of USA300 cells to attach to surfaces and form biofilms under both static and flow conditions.