Rapid genome-wide identification of genes required for infection would expedite studies bacterial pathogens. We developed genome-scale “negative selection” technology that combines high-density transposon mutagenesis and massively parallel sequencing transposon/chromosome junctions in a mutant library to identify mutants lost from the after exposure selective condition interest. This approach was applied comprehensively Haemophilus influenzae delay clearance murine pulmonary model. Mutations...

We used plants as an in vivo pathogenesis model for the identification of virulence factors human opportunistic pathogen Pseudomonas aeruginosa . Nine nine Tn phoA mutant derivatives P. strain UCBPP-PA14 that were identified a plant leaf assay less pathogenic mutants also exhibited significantly reduced pathogenicity burned mouse model, suggesting utilizes common strategies to infect both hosts. Seven these contain insertions previously unknown genes. These results demonstrate alternative...

Modifying surfaces using free radical polymerization (FRP) offers a means to incorporate the diverse physicochemical properties of vinyl polymers onto new materials. Here, we harness universal surface attachment polydopamine (PDA) "prime" range different for polymer attachment, including glass, cotton, paper, sponge, and stainless steel. We show that intrinsic species present in PDA can serve as an anchor point subsequent propagating macroradicals through radical–radical coupling. Leveraging...

The complete DNA sequence of Pseudomonas aeruginosa provides an opportunity to apply functional genomics a major human pathogen. A comparative approach combined with genetic footprinting was used as strategy identify genes required for viability in P. . Use highly efficient vivo mariner transposition system facilitated the analysis candidate this class. We have developed rapid and allelic exchange by using I- Sce I homing endonuclease conjunction vitro mutagenesis generate mutants within...

Enhanced cellular uptake and efficient penetration of nanocarriers inside tumors is paramount to successful anti-cancer therapy.

In nature, self-assembly processes based on amphiphilic molecules play an integral part in the design of structures higher order such as cells. Among them, glycoproteins or glycolipids take a pivotal role due to their bioactivity. Here we show that sugars, particular, fructose, are capable directing highly insoluble curcumin resulting formation well-defined capsules non-covalent forces. Simply by mixing aqueous solution fructose and open vessel leads generation with sizes ranging between 100...

Abstract Animal brains have evolved to encode social stimuli and transform these representations into advantageous behavioral responses. The commonalities differences of across species are not well-understood. Here, we show that isolation activates an oxytocinergic (OXT), nociceptive circuit in the larval zebrafish hypothalamus chemical cues released from conspecific animals potent modulators this circuit’s activity. We delineate olfactory subpallial pathway transmits OXT circuitry, where...

Summary Haemophilus influenzae transits between niches within the human host that are predicted to differ in oxygen levels. The ArcAB two‐component signal transduction system controls gene expression response respiratory conditions of growth and has been implicated bacterial pathogenesis, yet mechanism is not understood. We undertook a genome‐scale study identify genes H. ArcA regulon. Deletion arcA resulted increased anaerobic chain 's partial tricarboxylic acid cycle, decreased levels...

Significance The upper respiratory tract is colonized by numerous bacteria that are usually confined to this site in healthy individuals. However, coinfection with a preceding viral infection, these can colonize the lung, leading lethal secondary bacterial pneumonia. In report, frequent pathogen coinfections influenza virus, Haemophilus influenzae , was examined at whole-genome level comparatively analyze genes conferring fitness mice previously infected A virus vs. non-virally mice. We...

Albumin-based nanoparticles are widely used to delivery anticancer drug because they promote the accumulation of drugs in tumor sites. Nanoparticles with surface immobilized albumin described literature, although mixed systematically modified ratios between and PEG-based material less common. In this work, hybrid were prepared by coassembly a amphiphilic block copolymer together polymer-protein conjugate. Poly(oligo(ethylene glycol) methyl ether acrylate)-poly(ε-caprolactone) (POEGMEA-PCL)...

The ToxRS system in Vibrio cholerae plays a central role the modulation of virulence gene expression response to environmental stimuli. An integration multiple signalling inputs mediated by ToxR, -S, and -T controls leading cholera toxin (CT) production. Recently, we identified new locus, varA (virulence associated regulator), classical V. O1 that positively transcription tcpA, major subunit toxin-coregulated pilus (TCP) production CT, two key factors pathogenesis. locus is homolog gacA...

Zymogen granules of the exocrine pancreas are secretory organelles responsible for regulated secretion digestive enzymes. Several proteins associated with or integral components lipid bilayer that forms zymogen granule membrane. These likely represent important in VAMPs (vesicle-associated membrane proteins)/synaptobrevins a family 18-kDa originally characterized synaptic vesicles. Polyclonal antisera raised against either VAMP/glutathione S-transferase (GST) fusion protein rat brain...

Haemophilus influenzae efficiently colonizes and persists at the human nasopharyngeal mucosa, causing disease when it spreads to other sites. Nitric oxide (NO) represents a major antimicrobial defense deployed by host cells in locations colonized H. during pathogenesis that are likely vary oxygen levels. Formate-dependent nitrite reductase regulator (FNR) is an oxygen-sensitive several bacterial pathogens. We report fnr of required for anaerobic against exposure NO donors resist NO-dependent...

The formation of a non-specific protein corona around nanoparticles (NPs) has been identified as one the culprits for failed nanomedicine. amount and type adsorbed from blood plasma are known to determine fate NPs accessibility targeting ligands. Herein, we show that may not only enlarge change their surface properties but also, in case soft such polymer micelles, lead deformation. Poly(1-O-methacryloyl -β-D-fructopyranose)-b-poly(methylmethacrylate) (P(1-O-MAFru)-b-PMMA) block co-polymers...

ABSTRACT The Arc (anoxic redox control) two-component signal transduction system of Escherichia coli , which comprises the tripartite ArcB sensor kinase and ArcA response regulator, modulates expression numerous operons in to conditions growth. We demonstrate that arcA arcB genes Haemophilus influenzae specify a system. proteins two bacterial species sufficiently resemble each other they can participate heterologous transphosphorylation vitro. Moreover, H. mediates transcriptional control...

ABSTRACT Signaling mechanisms used by Haemophilus influenzae to adapt conditions it encounters during stages of infection and pathogenesis are not well understood. The ArcAB two-component signal transduction system controls gene expression in response respiratory growth contributes resistance bactericidal effects serum bloodstream H. . We show that ArcA nontypeable (NTHI) activates a glycosyltransferase gene, lic2B. Structural comparison the lipooligosaccharide (LOS) lic2B mutant wild-type...

Nontypeable Haemophilus influenzae (NTHi) cause a range of illnesses including otitis media, sinusitis, and exacerbation chronic obstructive pulmonary disease, infections that contribute to the problem antibiotic resistance are themselves often intractable standard treatment regimens. We investigated strategy exploit binding complement inhibitor Factor H (FH) NTHi as functional target for an immunotherapeutic containing domain FH fused Fc IgG1. Chimeric proteins regions most FH-binding...

Nontypeable Haemophilus influenzae (NTHi) is a major cause of community acquired pneumonia and exacerbation chronic obstructive pulmonary disease. A current effort in NTHi vaccine development has focused on generating humoral responses been greatly impeded by antigenic variation among the numerous circulating strains. In this study, we showed that immunization mice with killed generated broad protection against lung infection different While passive transfer immune antibodies protected only...

Herein we demonstrate a method for decorating highly reflective 2D gold microplates with magnetic nanoparticles to produce an optical colloid that can be actuated using applied field.

ABSTRACT Haemophilus influenzae is an obligate human pathogen that persistently colonizes the nasopharynx and causes disease when it invades bloodstream, lungs, or middle ear. Proteins mediate critical interactions with host during invasive are likely to be secreted. Many secreted proteins require addition of disulfide bonds by DsbA oxidoreductase for activity stability. In this study, we evaluated role in H. pathogenesis DsbA, as well HbpA, a substrate DsbA. Mutants Rd type b strain Eagan...

Co-delivery of two drugs in one nanoparticle is increasingly used to overcome, for example, multi-drug resistance cancer therapy and therefore suitable drug carriers need be developed.

Nontypeable

ABSTRACT Animal brains have evolved to encode social stimuli and transform these representations into advantageous behavioral responses. The commonalities differences of across species are not well-understood. Here, we show that isolation activates an oxytocinergic (OXT), nociceptive circuit in the larval zebrafish hypothalamus chemical cues released from conspecific animals potent modulators this circuit’s activity. We delineate olfactory subpallial pathway transmits OXT circuitry, where...