Lipopolysaccharides from Different Burkholderia Species with Different Lipid A Structures Induce Toll-Like Receptor 4 Activation and React with Melioidosis Patient Sera Host Response and Inflammation

Lipopolysaccharides (LPSs) of Gram-negative bacteria comprise lipid A, core, and O-polysaccharide (OPS) components. Studies have demonstrated that LPSs isolated from the pathogenic species Burkholderia pseudomallei and Burkholderia mallei and from less-pathogenic species, such as Burkholderia thailandensis, are potent immune stimulators. The LPS structure of B. pseudomallei, the causative agent of melioidosis, is highly conserved in isolates from Thailand; however, the LPSs isolated from other, related species have not been characterized to enable understanding of their immune recognition and antigenicities. Here, we describe the structural and immunological characteristics of the LPSs isolated from eight Burkholderia species and compare those for B. pseudomallei to those for the other seven species. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), gas chromatography (GC), SDS-PAGE, Toll-like receptor 4 (TLR4) stimulation, and immunoblot analysis were performed on these Burkholderia species. MALDI-TOF profiles demonstrated that Burkholderia lipid A contains predominantly penta-acylated species modified with 4-amino-4-deoxy-arabinose residues at both terminal phosphate groups. The lipid A could be differentiated based on mass differences at m/z 1,511, 1,642, 1,773, and 1,926 and on fatty acid composition. LPSs of all species induced TLR4-dependent NF-B responses; however, while SDS-PAGE analysis showed similar LPS ladder patter...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Host Response and Inflammation Source Type: research

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In this study, the therapeutic potential of combinations of an antibiotic and a broad-spectrum antimicrobial peptide (AMP) was evaluated against five bacterial biothreats, the etiologic agents of glanders (Burkholderia mallei), melioidosis (Burkholderia pseudomallei), plague (Yersinia pestis), tularemia (Francisella tularensis), and anthrax (Bacillus anthracis). The therapeutics included licensed early generation antibiotics which are now rarely used. Three antibiotics and one 24- amino acid AMP were selected based on MIC assay data. Combinations of the AMP and tigecycline, minocycline, or novobiocin were screened for syne...
Source: Microbial Pathogenesis - Category: Infectious Diseases Source Type: research
Abstract Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) cause the often-lethal infectious diseases melioidosis and glanders, respectively. Curiously, closely related species within the Bp complex share a nearly identical arsenal of virulence traits, yet are harmless to humans. Clues to the origin of virulence in this group can be found in their genetics and ecology. As a resident of the rhizosphere, Bp faces competition for nutrients and predation by other organisms. Adaptation over millennia has enabled Bp to accumulate mechanisms that overlap in their ability to promote fitness in the environment an...
Source: Current Opinion in Microbiology - Category: Microbiology Authors: Tags: Curr Opin Microbiol Source Type: research
Abstract To improve the preparedness against exposure to highly pathogenic bacteria and to anticipate the wide variety of bacteria that can cause bloodstream infections (BSIs), a safe, unbiased and highly accurate identification method was developed. Our liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method can identify highly pathogenic bacteria, their near-neighbors and bacteria that are common causes of BSIs directly from positive blood culture flasks. The developed Peptide-Based Microbe Detection Engine (http://proteome2pathogen.com) relies on a two-step workflow: a genus-level search followed...
Source: International Journal of Medical Microbiology - Category: Microbiology Authors: Tags: Int J Med Microbiol Source Type: research
Abstract Burkholderia pseudomallei (B. pseudomallei), the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care, but in the case of septicemia left untreated it can range from 50 - 90%. Current therapy for melioidosis is biphasic, consisting of parenteral acute-phase treatment for two weeks or longer, followed by oral eradication-phase treatment lasting several months. An effective oral therapeutic for outpatient treatment of acute-phase mel...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Tier-1 Select Agents that cause melioidosis and glanders, respectively. These are highly lethal human infections with limited therapeutic options. Intercellular spread is a hallmark of Burkholderia pathogenesis, and its prominent ties to virulence make it an attractive therapeutic target. We developed a...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: Biological Sciences Source Type: research
Org. Biomol. Chem., 2019, Accepted Manuscript DOI: 10.1039/C9OB01711A, PaperMaude Cloutier, Emmanilo Delar, Kevin Muru, Seynabou Ndong, Robert R. Hoyeck, Taniya Kaewarpai, Narisara Chantratita, Mary N. Burtnick, Paul J. Brett, Charles Gauthier Melioidosis and glanders, respectively caused by the Gram-negative bacteriaBurkholderia pseudomallei (Bp) andBurkholderia mallei(Bm), are considered as urgent public health issues in developing countries and potential bioterrorism agents.... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - Organic and Biomolecular Chemistry - Category: Molecular Biology Authors: Source Type: research
Burkholderia thailandensis is a model organism for human pathogens Burkholderia mallei and Burkholderia pseudomallei. The study of B. thailandensis peroxiredoxin is helpful for understanding the survival, pathogenic infection, and antibiotic resistance of its homologous species. Alkyl hydroperoxide reductase subunit C (AhpC) is an important peroxiredoxin involved in oxidative damage defense. Here, we report that BthAhpC exhibits broad specificity for peroxide substrates, including inorganic and organic peroxides and peroxynitrite. AhpC catalyzes the reduction of oxidants using the N-terminal conserved Cys57 as a peroxidati...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study, we report low-cost, green synthesis of AgNPs using fresh fruit extract of Phyllanthus emblica. The biosynthesized AgNPs was confirmed and characterized by analysis of spectroscopy profile of the UV-visible and Energy dispersive spectrophotometer, Fourier transform infrared, X-ray diffraction pattern, and electron microscopy images examination. UV-visible spectra showed a surface resonance peak of 430 nm corresponding to the formation of AgNPs, and FTIR spectra confirmed the involvement of biological molecules in AgNPs synthesis. In spherical AgNPs, the particle size ranged from 19.8 to 92.8 nm and the averag...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
For Yersinia pestis, Burkholderia pseudomallei, and Burkholderia mallei, conventional broth microdilution (BMD) is considered the gold standard for antimicrobial susceptibility testing (AST) and, depending on the...
Source: BMC Microbiology - Category: Microbiology Authors: Tags: Research article Source Type: research
Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) sample preparation methods, including the direct, on-plate formic acid, and ethanol/formic acid tube extraction methods, were evaluated for their ability to render highly pathogenic organisms nonviable and safe for handling in a biosafety level 2 laboratory. Of these, the tube extraction procedure was the most successful, with none of the tested strains surviving this sample preparation method. Tube extracts from several agents of bioterrorism and their near neighbors were analyzed in an eight-laboratory study to examine the u...
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Bacteriology Source Type: research
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