ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa is a leading cause of nosocomial pneumonia. Among its virulence factors, the type IV pili P. strain 1244 contain covalently linked, three-sugar glycan previously unknown significance. work described in this paper was carried out to determine influence pilin on pilus function, as well possible role pathogenesis. To accomplish this, deletion introduced into pilO gene organism. isogenic knockout produced, 1244G7, unable glycosylate but...

Abstract Background After infecting a mammalian host, the facultative intracellular bacterium, Francisella tularensis , encounters an elevated environmental temperature. We hypothesized that this temperature change may regulate genes essential for infection. Results Microarray analysis of F. LVS shifted from 26°C (environmental) to 37°C (mammalian) showed ~11% bacterium's were differentially-regulated. Importantly, 40% protein-coding induced at have been previously implicated in virulence or...

ABSTRACT The pathogenesis of Francisella tularensis has been associated with this bacterium's ability to replicate within macrophages. F. can also invade and in a variety nonphagocytic host cells, including lung kidney epithelial cells hepatocytes. As uracil biosynthesis is central metabolic pathway usually necessary for pathogens, we characterized Δ pyrF mutants both LVS Schu S4 investigate the role these intracellular growth. expected, mutant strains were deficient de novo pyrimidine...

Microbial infections are a major cause of infant mortality worldwide because impaired immune defences in this population. The nature work was to further understand the mechanistic limitations neonatal and response. Interleukin-27 (IL-27) is heterodimeric cytokine IL-12 family that produced primarily by antigen-presenting cells immunosuppressive toward variety cell types. We show IL-27 gene expression elevated cord blood-derived macrophages relative originating from healthy adults. also...

The highly infectious and deadly pathogen, Francisella tularensis, is classified by the CDC as a Category A bioterrorism agent. Inhalation of single bacterium results in an acute pneumonia with 30-60% mortality rate without treatment. Due to prevalence antibiotic resistance, there strong need for new types antibacterial drugs. Resazurin commonly used measure bacterial eukaryotic cell viability through its reduction fluorescent product resorufin. When tested on various taxa at recommended...

ABSTRACT Tularemia is caused by the category A biodefense agent Francisella tularensis . This bacterium associated with diverse environments and a plethora of arthropod mammalian hosts. How F. adapts to these different conditions, particularly eukaryotic intracellular environment in which it replicates, poorly understood. Here, we demonstrate that polyamines spermine spermidine are environmental signals alter bacterial stimulation host cells. Genomewide analysis showed LVS undergoes...

The O antigen is both a major structural outer membrane component and the dominant epitope of most gram-negative bacteria. Pseudomonas aeruginosa 1244 produces type IV pilus covalently links an O-antigen repeating unit to each pilin monomer. Here we show that immunization mice with pure from strain by use either mouse respiratory model or thermal injury resulted in protection challenge pilus-null O-antigen-producing mutant. These results provide evidence glycan stimulates protective response...

Tularemia is a debilitating febrile illness caused by the category A biodefense agent Francisella tularensis. This pathogen infects over 250 different hosts, has low infectious dose, and causes high morbidity mortality. Our understanding of mechanisms which F. tularensis senses adapts to host environments incomplete. Polyamines, including spermine, regulate interactions with cells. However, it not known whether responsiveness polyamines necessary for virulence organism. Through transposon...

Francisella tularensis is the causative agent of tularemia and classified as a category A biodefense by Centers for Disease Control Prevention because its highly infectious nature. F. infects leukocytes exhibits an extracellular phase in blood host. It unknown, however, whether can infect erythrocytes; thus, we examined this possibility vivo vitro. In murine model pulmonary type tularemia, showed presence intraerythrocytic bacteria double-immunofluorescence microscopy ex gentamicin...

Medical devices, such as contact lenses, bring bacteria in direct with human cells. Consequences of these host-pathogen interactions include the alteration mammalian cell surface architecture and induction cellular death that renders tissues more susceptible to infection. Gram-negative known induce blebbing by cells, Pseudomonas Vibrio species, do so through a type III secretion system-dependent mechanism. This study demonstrates subset from Enterobacteriaceae bacterial family membrane blebs...

Francisella tularensis is a pathogenic intracellular bacterium and the causative agent of zoonotic disease tularemia. The CDC classifies F. as Tier 1 select due to its potential for misuse biological weapon, given low infectious dose capacity produce fatal pneumonic infection. Furthermore, naturally occurring subspecies are known cause numerous human infections through exposure various blood-sucking arthropods contaminated animal hosts. Prior research conducted in our laboratory has...

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogenic gram-positive bacterium. MRSA poses significant risk to public health because this bacterium resistant beta-lactam antibiotics among others. In the United States alone, was estimated cause 70,000 infections and 9,000 deaths yearly. Therefore, continuous drug discovery necessary for decreasing MRSA-related deaths. Our laboratory screened an extract library from National Center Natural Products Research identify potential novel...

Pseudomonas aeruginosa is drug-resistant pathogen that commonly acquired during hospital stays. This bacterium produces type IV pili which are adhesins and motor appendages mediate a surface motility referred to as “twitching.” These polymers of protein subunits pilin. The pilin subunit P. 1244 glycosylated. Previous studies have shown the glycan affects efficiency twitching under certain conditions polarity these fibers. We tested whether glass surfaces, EDTA, spermine, or CTAB affected...

Francisella tularensis is a pathogenic gram-negative bacterium that causes the zoonotic disease Tularemia. In addition, F. classified as Class A Bioterrorism agent by CDC due to ease of aerosolization and ability this cause fatal infection in low doses. Previous studies suggest invasion mammalian erythrocytes increases colonization ticks, an arthropod vector pathogen. Our laboratory previously found erythrocyte membrane glycoprotein, Band 3 required for red blood cells. Therefore, we predict...

Peptidoglycan (PG), the main component of bacterial cell wall, plays a fundamental role in maintaining shape, integrity, and resistance to osmotic pressure. Preliminary observations suggested that unlike typical bacteria, Francisella tularensis infrequently produces detectable PG while growing rich liquid media. However, increasing salt concentration induces production all bacteria. In this study, we confirmed extended these by incubating bacteria with fluorescent D-alanine (which integrates...

Francisella tularensis is an intracellular bacterium and the causative agent of zoonotic disease, tularemia. F. invades host erythrocytes during infection, a phenomenon that leads to increased colonization ticks after blood meal. To better understand mechanism erythrocyte invasion, RNA-seq analysis was conducted identify genes whose transcription affected by presence erythrocytes. A putative Zinc/ferric uptake regulator gene, FTL_1199 identified. Therefore, we hypothesized this gene may play...

ABSTRACT The pilin of Pseudomonas aeruginosa 1244 is glycosylated with an oligosaccharide that structurally identical to the O-antigen repeating unit this organism. Concordantly, metabolic source glycan biosynthetic pathway. present study was conducted investigate substrate recognition in glycosylation reaction. Comparative structural analysis O subunits had been previously shown be compatible machinery revealed similarities among sugars at presumed reducing termini these oligosaccharides....

In the United States, roughly $600 billion is spent on pain management -usually in form of addictive opioid drugs.Due to dangers associated with long-term opiate-based medication, development additional strategies for chronic warranted.The advent smartphones and technology has provided healthcare providers a unique opportunity provide support.This review summarizes use supplement regimens.Smartphone internetbased applications that employ online journals facilitate improved communication...

The inauguration of novel treatment strategies into the clinical setting faces a number hurdles. In addition to efficacy and safety, acceptance by doctors patients is paramount success therapies. Although viruses are cause numerous infectious diseases, these acellular entities have been harnessed over years benefit mankind. Recently, recombinant Poliovirus-Rhinovirus Chimera (PVSRIPO) has shown promise for glioblastoma in trials as well other cancer types animal models. this literature...

The beta-carbon of the Pseudomonas aeruginosa 1244 pilin C-terminal Ser is a site glycosylation. present study was conducted to determine structures necessary for It found that although Thr could be tolerated at C terminus, blocking carboxyl group with addition an Ala prevented Pilin from strain PA103 not glycosylated by P. 1244, even when residue converted Ser. Substituting disulfide loop region allowed glycosylation take place. Neither conversion Cys residues nor deletion segments this...

Francisella tularensis, the causative agent of tularemia, is a category A biodefense agent. The examination gene function in this organism limited due to lack available controllable promoters. Here, we identify promoter element F. tularensis LVS that repressed by glucose (termed glucose-repressible promoter, or FGRp), allowing management downstream expression. In bacteria cultured medium lacking glucose, induced expression red fluorescent protein allele, tdtomato. FGRp activity was used...

Francisella tularensis is a gram-negative, intracellular pathogen which can cause serious, potentially fatal, illness in humans. Species of F. are found across the Northern Hemisphere and infect broad range host species, including Factors affecting persistence environment its epidemiology not well understood, however, ability to enter viable but non-culturable state (VBNC) may be important. A bacteria, many pathogens, have been observed VBNC response stressful environmental conditions, such...