An improved dental composite with potent antibacterial function

A new BisGMA-based antibacterial dental composite has been formulated and evaluated. Compressive strength and bacterial viability were utilized to evaluate the formed composites. It was found that the new composite exhibited a significantly enhanced antibacterial function along with improved mechanical and physical properties. The bromine-containing derivative-modified composite was more potent in antibacterial activity than the chlorine-containing composite. The modified composites also exhibited an increase of 30–53% in compressive yield strength, 15–30% in compressive modulus, 15–33% in diametral tensile strength and 6–20% in flexural strength, and a decrease of 57–76% in bacterial viability, 23–37% in water sorption, 8–15% in shrinkage, 8–13% in compressive strength, and similar degree of conversion, than unmodified composite. It appears that this experimental composite may possibly be introduced to dental clinics as an attractive dental restorative due to its improved properties as well as enhanced antibacterial function

Does Magnesium Transport Protein (MgtE) Contribute to the Antibiotic Resistance of Pseudomonas aeruginosa?

poster abstractPseudomonas aeruginosa is an environmental and opportunistic bacterial pathogen that is resistant to antibiotic treatment when it forms biofilms in the lungs of patients with cystic fibrosis. Biofilms are densely packed communities of bacteria embedded within a self-produced matrix of extracellular polymeric substance (EPS). Biofilm EPS is a polymeric cluster composed of extracellular DNA, proteins and polysaccharides. Based on previous studies, in a low Mg2+ environment, P. aeruginosa wild-type is less or non-resistant to antibiotics and in a high Mg2+ environment, P. aeruginosa is more resistant to antibiotics. The purpose of this project was to find out if the magnesium transport protein (MgtE) is a contributor to the antibiotic resistance of P. aeruginosa .This was accomplished by using two different strains of P.aeruginosa; PA14 wild-type and GGA52 mutant (without the magnesium transporting protein). Four antibiotics were used; gentamicin, tobramycin, ciproflaxin and imipenem. The minimum inhibitory concentration (MIC) of each antibiotic was determined by culturing the bacteria strains on LB agar plates and use Etest strips to observe growth. N-minimal media supplemented with varying magnesium concentration was used to test if Mg2+ increased or reduced the antibiotic resistance at the MIC of P. aeruginosa as well as counting bacterial colonies. The mutant strain (GGA52) is expected to be less resistant than the wild type strain (PA14) because it does not have MgtE. If these predictions are true, then MgtE is an important contributor to the antibiotic resistance of P. aeruginosa. These results can be helpful in understanding the mechanism of antibiotic resistance of P. aeruginosa in patients with cystic fibrosis

The Regulatory Protein AlgR Influences Pseudomonas aeruginosa Pathogenesis on Airway Cells

poster abstractOne of the primary causes of high mortality in patients with Cystic Fibrosis (CF) is lung infection caused by the Gram-negative bacterium Pseudomonas aeruginosa. In the lungs of such patients, this bacterium forms lifelong infections, characterized by biofilm formation. Our goal is to identify factors that influence P. aeruginosa biofilm formation in the CF airways. Using a novel model of biofilm formation on cultured human CF airway cells, we found that mutation of the gene algR resulted in significant reduction in the ability to form biofilms as well as adhere to CF airway cells. When algR gene activity was restored in these deletion mutant strains, by an algR complementation plasmid, adherence improved to a level similar to that of the wild type P. aeruginosa strain, and biofilm production was also restored significantly. Additionally, e observed the effects of AlgR on transcription of the Type III Secretion System (T3SS), and found that AlgR might be influence regulation of T3SS activity through the magnesium transporter protein MgtE. Altogether, our results point to a role for AlgR in biofilm formation on CF airway cells through modulation of T3SS as well as adherence. Through this and additional studies, such as investigation of cross-talk between AlgR and other genes such as MgtE, which is a putative virulence modulator in P. aeruginosa, we aim to get a more lucid understanding of the molecular mechanisms responsible for persistence of lifelong P. aeruginosa biofilms in lungs of CF patients

Pseudomonas Aeruginosa Biofilm Formation in Different Environments

poster abstractVarious bacteria, such as the soil microbe Pseudomonas aeruginosa, form into strong structures to defend themselves from antibiotics and other harmful materials. These structures are called biofilms. The goal of this research is to isolate P. aeruginosa from several soil samples and determine whether they are able to form biofilms in those environments. Another goal of this research is to find out how different environmental factors affect the formation of Pseudomonas biofilms. We isolated P. aeruginosa from soil samples using Pseudomonas Isolation Agar plates. The colonies most similar to P. aeruginosa were picked, cultured, and tested by PCR in order to confirm that the strains were actually P. aeruginosa. Using these methods, so far we have collected 12 P. aeruginosa strains and we are collecting more strains from different soil samples. In future studies, we will determine whether these strains form biofilms in soil. We will also demonstrate the effect of magnesium on P. aeruginosa on biofilm formation. These studies will begin to investigate how altering environmental conditions can influence persistence of this bacterial pathogen in the soil. These studies can have broad implications for transmission of the bacterium from the environment to humans during disease

THE EFFECTS OF QUORUM SENSING ANTAGONISTS ON BIOFILM

poster abstractCystic fibrosis (CF) is a recessive genetic disorder that causes the for-mation of thick mucus plugs in the lungs of approximately 30,000 people in the United States and 60,000 individuals world-wide. Pseudomonas aeruginosa, an opportunistic bacterial pathogen, is able to colonize the mu-cus plugs and form antibiotic resistant biofilms. These microbial colonies, known as biofilms, cause serious problems for individuals living with CF. P. aeruginosa biofilms are able to cause chronic infections in the lungs of CF patients leading to increased morbidity and mortality. Using a modified bio-film assay, we tested the effects of modified chemical compounds and amino acids on P. aeruginosa biofilm dispersion. A previous study performed on P. aeruginosa, found that treatment of d- and l- amino acids resulted in biofilm dissemination. Through additional experiments, we will identify modified chemical compounds that induce biofilm dispersion. This research will in-crease our knowledge of P. aeruginosa biofilm dispersion, and allow us to explore new forms of treatment and therapy for CF patients with chronic in-fections that could be life threatening

DOES LOW MAGNESIUM IN CYSTIC FIBROSIS CONTRIBUTE TO BACTERIAL PATHOGENICITY?

poster abstractCystic fibrosis (CF) is a genetic disease for which there is currently no cure. Individuals with CF are plagued by myriad symptoms, including chronic pneumonia, which diminishes quality of life and reduces life expectancy to 40 years. The most common bacterium in CF patients’ lungs is Pseudomonas aeruginosa, a highly adaptable organism capable of surviving robust antibi-otic treatment. At the heart of developing improved treatments for CF pa-tients is the need to better understand P. aeruginosa pathogenicity. To this end, we have been studying the role of magnesium, which is often found at below normal levels in CF patients. Magnesium is an essential element in numerous cellular functions in both bacteria and humans. In previous re-search, we developed a P. aeruginosa strain with a deletion of the magnesi-um transport protein MgtE, as well as 16 plasmids carrying different muta-tions of the mgtE gene. Experiments with these constructs demonstrated a relationship between magnesium transport and bacterial toxin production. In the research presented here, we hypothesize that lower levels of magnesium may trigger a bacterial response, causing a change in P. aeruginosa patho-genicity. Changes may include differential growth, toxin release, and for-mation of biofilms, which are surface-adhered, antibiotic tolerant bacterial communities in a protective polysaccharide matrix. Using various magnesi-um levels, we have measured P. aeruginosa growth rates, motility, biofilm formation, and cytotoxicity toward cultured cells derived from the CF bron-chial epithelium. Preliminary results suggest that lower magnesium contrib-utes to changes in the bacterium that favor persistence in the CF lung. On-going studies include the effect of long-term growth of P. aeruginosa in low magnesium and how this impacts a number of virulence factors. We antici-pate that our research will elucidate the relationship between magnesium and P. aeruginosa pathogenicity and potentially lead to improved treatments for CF patients

Development of a New in vitro System for Cystic Fibrosis Research

poster abstractIndividuals with cystic fibrosis (CF) have a life expectancy of 40 years and require daily treatments to mitigate the effects of the disease. CF impacts organs throughout the body, especially the lungs, where thick mucus builds up, impairs breathing, and provides an environment for bacterial growth. Chronic lung infection is the leading cause of mortality in CF. The majority of CF lung infections are caused by Pseudomonas aeruginosa, a common bacterium which typically does not cause disease in healthy individuals. In the CF lung, however, P. aeruginosa burrows into the thick mucus layer, evades the immune system, and resists antibiotic therapy by encasing itself in a protective matrix called a biofilm. Laboratory methods for studying biofilm are not true replicas of the CF lung environment, leaving a knowledge gap between how bacteria grow in a test tube (in vitro) and how they grow in the lungs of a person with CF. The focus of this work is to develop an improved laboratory model which combines artificial sputum (as a surrogate for mucus in the CF lung) and cultured CF airway epithelial cells. To assess the potential of this model, we have performed experiments to compare P. aeruginosa in artificial sputum versus standard laboratory media. Results demonstrate that P. aeruginosa in artificial sputum exhibits differences in growth, biofilm formation, toxin production, cytotoxicity, and protein expression, compared to results in standard media. These data suggest that our model system can contribute new information to the understanding of CF airway infection. The aim of future studies is to use this system to identify sputum components and bacterial proteins which have not been recognized previously by standard methods. It is our ultimate goal to contribute knowledge leading to improved longevity and quality of life for people with CF

Going After Lipotoxins to Reduce Inflammation in the Airway of Cystic Fibrosis Patients

poster abstractPeople with cystic fibrosis (CF) typically have chronic lung infections, predominantly with Pseudomonas aeruginosa. Lung inflammation, in connection with bacterial colonization, is one of the major factors contributing to the morbidity and mortality of CF patients. Recent studies suggest that a common mutation among CF P. aeruginosa isolates (in the gene mucA) results in high-level expression of lipoproteins which stimulates a pro-inflammatory reaction in cultured CF-derived airways cell (CFBE). Our previous work in this area has revealed that a strain containing a mutation in the putative lipotoxin gene PA4326 is dramatically less toxic to CFBE. We hypothesize that lipotoxins lead to airway structure damage by causing epithelial cell death and tissue destruction, possibly as a downstream effect of immune stimulation. Our results demonstrate that deletion of the PA4326 gene does not affect growth, motility, adhesion, or biofilm development. However, this mutant strain produces 59.1% less pyocyanin compared to the non-mutant strain. Pyocyanin is a bacterial toxin that triggers airway inflammation by stimulating the immune system to produce the signaling molecule IL-8. Thus, our data suggest a possible clue about the decreased toxicity of the PA4325 mutant. The aim of future work is to confirm the role of this lipotoxin gene in the inflammatory process and to elucidate the underlying mechanism of its function. Our long term goal is to characterize other lipotoxins and to develop a novel inhibitor of lspA (a bacterial gene required for lipotoxin production) as an anti-inflammatory strategy to slow down the airway damage and hence improve the longevity and quality of life for people with CF

Excess Observed in CDF Bs0→μ+μ−B^0_s \to \mu^{+} \mu^{-} and SUSY at the LHC

The recent excess observed by CDF in $B^0_s \to \mu^{+} \mu^{-}$ is interpreted in terms of a possible supersymmetric origin. An analysis is given of the parameter space of mSUGRA and non-universal SUGRA models under the combined constraints from LHC-7 with 165 pb$^{-1}$ of integrated luminosity, under the new XENON-100 limits on the neutralino-proton spin independent cross section and under the CDF $B^0_s \to \mu^{+} \mu^{-}$ 90% C.L. limit reported to arise from an excess number of dimuon events. It is found that the predicted value of the branching ratio $B^0_s \to \mu^{+} \mu^{-}$ consistent with all the constraints contains the following set of NLSPs: chargino, stau, stop or CP odd (even) Higgs. The lower bounds of sparticles, including those from the LHC, XENON and CDF $B^0_s\to \mu^+\mu^-$ constraint, are exhibited and the shift in the allowed range of sparticle masses arising solely due to the extra constraint from the CDF result is given. It is pointed out that the two sided CDF 90% C.L. limit puts upper bounds on sparticle masses. An analysis of possible signatures for early discovery at the LHC is carried out corresponding to the signal region in $B^0_s \to \mu^{+} \mu^{-}$. Implications of GUT-scale non-universalities in the gaugino and Higgs sectors are discussed. If the excess seen by the CDF Collaboration is supported by further data from LHCb or D0, this new result could be a harbinger for the discovery of supersymmetry.Comment: References added, text update