Layering vaccination with antibiotic therapy results in protection and clearance of in Balb/c mice.

Melioidosis is a disease that is difficult to treat due to the causative organism, being inherently antibiotic resistant and it having the ability to invade, survive, and replicate in an intracellular environment. Combination therapy approaches are routinely being evaluated in animal models with the aim of improving the level of protection and clearance of colonizing bacteria detected. In this study, a subunit vaccine layered with the antibiotic finafloxacin was evaluated against an inhalational infection with in Balb/c mice.

An Investigation into the Re-Emergence of Disease Following Cessation of Antibiotic Treatment in Balb/c Mice Infected with Inhalational .

is the causative agent of melioidosis, a multifaceted disease. A proportion of the mortality and morbidity reported as a result of infection with this organism may be due to the premature cessation of antibiotic therapy typically lasting for several months. The progression of re-emergent disease was characterised in Balb/c mice following cessation of a 14 day treatment course of co-trimoxazole or finafloxacin, delivered at a human equivalent dose.

Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

Background: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel.

Laboratory Structure And Resource: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists.

Finafloxacin Is an Effective Treatment for Inhalational Tularemia and Plague in Mouse Models of Infection.

Infection with aerosolized or can lead to lethal disease in humans if treatment is not initiated promptly. Finafloxacin is a novel fluoroquinolone which has demonstrated broad-spectrum activity against a range of bacterial species , and in humans, activity which is superior in acidic, infection-relevant conditions. Human-equivalent doses of finafloxacin or ciprofloxacin were delivered at 24 h (representing prophylaxis) or at 72 or 38 h (representing treatment) postchallenge with or , respectively, in BALB/c mouse models.

Role of DNA Repair and Protective Components in Bacillus subtilis Spore Resistance to Inactivation by 400-nm-Wavelength Blue Light.

The high intrinsic decontamination resistance of spores is important medically (disease) and commercially (food spoilage). Effective methods of spore eradication would be of considerable interest in the health care and medical product industries, particularly if the decontamination method effectively killed spores while remaining benign to both humans and sensitive equipment. Intense blue light at a ∼400 nm wavelength is one such treatment that has drawn significant interest.

Species-specific antifungal activity of blue light.

Fungal pathogens represent a significant threat to immunocompromised patients or individuals with traumatic injury. Strategies to efficiently remove fungal spores from hospital surfaces and, ideally, patient skin thus offer the prospect of dramatically reducing infections in at-risk patients. Photodynamic inactivation of microbial cells using light holds considerable potential as a non-invasive, minimally destructive disinfection strategy.

Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy.

Toll-like receptors (TLRs) recognise invading pathogens and mediate downstream immune signalling via Toll/IL-1 receptor (TIR) domains. TIR domain proteins (Tdps) have been identified in multiple pathogenic bacteria and have recently been implicated as negative regulators of host innate immune activation. A Tdp has been identified in Bacillus anthracis, the causative agent of anthrax.

Antibacterial Activity of Blue Light against Nosocomial Wound Pathogens Growing Planktonically and as Mature Biofilms.

Unlabelled: The blue wavelengths within the visible light spectrum are intrinisically antimicrobial and can photodynamically inactivate the cells of a wide spectrum of bacteria (Gram positive and negative) and fungi. Furthermore, blue light is equally effective against both drug-sensitive and -resistant members of target species and is less detrimental to mammalian cells than is UV radiation. Blue light is currently used for treating acnes vulgaris and Helicobacter pylori infections; the utility for decontamination and treatment of wound infections is in its infancy.

Improvement of Biological Indicators by Uniformly Distributing Bacillus subtilis Spores in Monolayers To Evaluate Enhanced Spore Decontamination Technologies.

Novel decontamination technologies, including cold low-pressure plasma and blue light (400 nm), are promising alternatives to conventional surface decontamination methods. However, the standardization of the assessment of such sterilization processes remains to be accomplished. Bacterial endospores of the genera Bacillus and Geobacillus are frequently used as biological indicators (BIs) of sterility.

Trimethoprim/sulfamethoxazole (co-trimoxazole) prophylaxis is effective against acute murine inhalational melioidosis and glanders.

Burkholderia pseudomallei is the causative agent of the disease melioidosis, which is prevalent in tropical countries and is intractable to a number of antibiotics. In this study, the antibiotic co-trimoxazole (trimethoprim/sulfamethoxazole) was assessed for the post-exposure prophylaxis of experimental infection in mice with B. pseudomallei and its close phylogenetic relative Burkholderia mallei, the causative agent of glanders.

Design and characterization of novel hybrid antimicrobial peptides based on cecropin A, LL-37 and magainin II.

Antimicrobial peptides (AMPs) are a naturally occurring component of the innate immune response of many organisms and can have activity against both Gram-negative and Gram-positive bacterial species. In order to optimize and improve the direct antimicrobial effect of AMPs against a broad spectrum of bacterial species, novel synthetic hybrids were rationally designed from cecropin A, LL-37 and magainin II. AMPs were selected based on their α-helical secondary structure and fragments of these were analyzed and combined in silico to determine which hybrid peptides would form the best amphipathic cationic α-helices.

A carpet-based mechanism for direct antimicrobial peptide activity against vaccinia virus membranes.

Antimicrobial peptides have activity against a wide variety of biological membranes and are an important component of innate immunity in vertebrate as well as invertebrate systems. The mechanisms of action of these peptides are incompletely understood and a number of competing but not necessarily mutually exclusive models exist. In this study we examined the virucidal activity of four peptides, the human cathelicidin derived LL37, Xenopus alanine-substituted Magainin-2 amide, uperin-3.

The cationic peptide magainin II is antimicrobial for Burkholderia cepacia-complex strains.

This study was undertaken to determine the antibacterial activity of eight cationic antimicrobial peptides towards strains of genomovars I-V of the Burkholderia cepacia complex (Bcc) in time-kill assays. All but one of the peptides failed to show activity against the panel of test strains. The exception was magainin II, a 23 aa peptide isolated from the epidermis of the African clawed frog, Xenopus laevis, which exhibited significant bactericidal activity for Bcc genomovars most frequently associated with lung infection of patients with cystic fibrosis.

Differential cell surface properties of vegetative Bacillus.

Aims: The genus Bacillus encompasses a wide range of species which display varying pathogenic abilities. The hydrophobicity of a range of Bacillus species was determined to evaluate the correlation between bacterial hydrophobicity and pathogenicity.

Methods And Results: Bacterial adhesion to hydrocarbon assays were used to determine the hydrophobicity of various Bacillus species.

Polysaccharides and virulence of Burkholderia pseudomallei.

Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease of humans and animals. Gene clusters which encode capsular polysaccharide (type I O-PS) and LPS (type II O-PS), both of which play roles in virulence, have previously been identified. Here, the identification of two further putative clusters, type III O-PS and type IV O-PS, is reported.

Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis.

Bacillus anthracis is the causative agent of anthrax, a disease that affects wildlife, livestock, and humans. Protection against anthrax is primarily afforded by immunity to the B. anthracis protective antigen (PA), particularly PA domains 4 and 1.

Proteolytic degradation of human antimicrobial peptide LL-37 by Bacillus anthracis may contribute to virulence.

In this paper we report on the susceptibilities of a range of Bacillus species to the human antimicrobial peptide LL-37. B. subtilis showed a low level of resistance to killing by LL-37 (50% growth-inhibitory concentration [GI50], 1 microg/ml).

Production of Bacillus anthracis protective antigen is dependent on the extracellular chaperone, PrsA.

Protective antigen (PA) is a component of the Bacillus anthracis lethal and edema toxins and the basis of the current anthrax vaccine. In its heptameric form, PA targets host cells and internalizes the enzymatically active components of the toxins, namely lethal and edema factors. PA and other toxin components are secreted from B.

Optimization of the cell wall microenvironment allows increased production of recombinant Bacillus anthracis protective antigen from B. subtilis.

The stability of heterologous proteins secreted by gram-positive bacteria is greatly influenced by the microenvironment on the trans side of the cytoplasmic membrane, and secreted heterologous proteins are susceptible to rapid degradation by host cell proteases. In Bacillus subtilis, degradation occurs either as the proteins emerge from the presecretory translocase and prior to folding into their native conformation or after the native conformation has been reached. The former process generally involves membrane- and/or cell wall-bound proteases, while the latter involves proteases that are released into the culture medium.

D-Alanine substitution of teichoic acids as a modulator of protein folding and stability at the cytoplasmic membrane/cell wall interface of Bacillus subtilis.

The extracytoplasmic folding of secreted proteins in Gram-positive bacteria is influenced by the microenvironment of the compartment into which they are translocated, namely the negatively charged matrix of the cell wall polymers. In this compartment, the PrsA lipoprotein facilitates correct post-translocational folding or prevents misfolding of secreted proteins. In this study, a secretion mutant of B.

Complementary therapies: a patient's choice.

Judith Thwaite discusses the role of complementary therapy in her treatment for non-Hodgkins lymphoma. She was diagnosed with non-Hodgkins lymphoma in 1988 and since that time she has tried a number of therapies. A visit to the Bristol Cancer Help Centre changed her outlook on life and the Centre's policy of patient empowerment encouraged her to fulfil an ambition to write.