Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute and chronic infections in immunocompromised individuals. This gram-negative bacterium produces a battery of virulence factors that allow it to infect and survive in many different hostile environments. The control of many of these virulence factors falls under the influence of one of three P. aeruginosa cell-to-cell signaling systems. The focus of this study, the quinolone signaling system, functions through the Pseudomonas quinolone signal (PQS), previously identified as 2-heptyl-3-hydroxy-4-quinolone. This signal binds to and activates the LysR-type transcriptional regulator PqsR (also known as MvfR), which in turn induces the expression of the pqsABCDE operon. The first four genes of this operon are required for PQS synthesis, but the fifth gene, pqsE, is not. The function of the pqsE gene is not known, but it is required for the production of multiple PQS-controlled virulence factors and for virulence in multiple models of infection. In this report, we show that PqsE can activate PQS-controlled genes in the absence of PqsR and PQS. Our data also suggest that the regulatory activity of PqsE requires RhlR and indicate that a pqsE mutant can be complemented for pyocyanin production by a large excess of exogenous N-butyryl homoserine lactone (C 4 -HSL). Finally, we show that PqsE enhances the ability of Escherichia coli expressing RhlR to respond to C 4 -HSL. Overall, our data lead us to conclude that PqsE functions as a regulator that is independent of PqsR and PQS but dependent on the rhl quorum-sensing system.Pseudomonas aeruginosa is a serious opportunistic pathogen that can cause infections in a diverse group of organisms from the animal, plant, and insect kingdoms (9, 47, 53). In humans, P. aeruginosa can cause multiple types of infections that are generally difficult to treat due to the high level of antibiotic resistance exhibited by this microbe (15). These infections are complex and generally involve numerous virulence determinants, with some factors playing a larger role than others in different types of infections (16). One aspect of P. aeruginosa virulence that seems to be important in most infections is the ability of the bacteria to communicate via intercellular signals (11). P. aeruginosa uses at least three cell-to-cell signaling systems to control the expression of assorted virulence factors. There are two classical acyl-homoserine lactone (HSL)-based quorum-sensing systems, the las and rhl systems (see reference 43 for a review of P. aeruginosa quorum sensing). The las and rhl quorum-sensing systems function via the signals N-(3-oxododecanoyl) HSL (3-oxo-C 12 -HSL) and N-butyryl HSL (C 4 -HSL), respectively (40, 41). When at a threshold concentration, 3-oxo-C 12 -HSL and C 4 -HSL serve as coinducers for the transcriptional activators LasR and RhlR, respectively (21,35,36,39). The other cell-to-cell signaling system of P. aeruginosa functions through the quinolone compound 2-heptyl-3-hydroxy-4-quinolone (the Pseudomonas ...
Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, clinical situations in which phage therapy might be considered, dosing, route of administration, and outcomes. Large gaps in knowledge contribute to a heterogeneity in approach and lack of clear consensus in many important clinical areas. Here, the Antibacterial Resistance Leadership Group (ARLG) has convened a panel of experts in phage therapy, clinical microbiology, infectious diseases, and pharmacology, who worked with regulatory experts and a funding agency to identify questions based on a clinical framework and divided them into three themes: potential clinical situations in which phage therapy might be considered, and laboratory testing and pharmacokinetic considerations. Suggestions are provided as answers to a series of questions intended to inform clinicians considering experimental phage therapy for patients in their clinical practices.
Introduction Cardiomyopathy is a common cause of morbidity and death in patients with Duchenne muscular dystrophy (DMD). Methods A cross-sectional analysis of clinical data from a multi-institutional, international CINRG DMD Natural History Study of 340 DMD patients aged 2 to 28 years. Cardiomyopathy was defined as shortening fraction (SF) <28% or ejection fraction (EF) <55%. Results 231 participants reported a prior clinical echocardiogram study, and 174 had data for SF or EF. The prevalence of cardiomyopathy was 27% (47/174), and it was significantly associated with age and clinical stage. The association of cardiomyopathy with age and clinical stage was not changed by glucocorticoid use as a covariate (P>0.68). In patients with cardiomyopathy, 57 % (27/47) reported not taking any cardiac medications. Cardiac medications were used in 12% (15/127) of patients without cardiomyopathy. Discussion Echocardiograms were underutilized, and cardiomyopathy was undertreated in this DMD natural history cohort.
New technologies have allowed remote real-time electronic recording of symptoms and spirometry. The feasibility of utilising this technology in COPD patients has not been investigated. This is a feasibility study. The primary objective is to determine whether the use of an electronic diary with a portable spirometer can be performed by COPD patients with a moderate to severe disease. Secondary objectives are to investigate the value of this method in early detection of acute exacerbations of COPD (AECOPD). In this 6-month study, 18 patients recorded daily their symptom score and spirometry. Data was sent on real time. AECOPD which was defined according to pre-set criteria were noted. Spirometry values and scores for health-related quality of life were compared between the start and the end of the study. Hospitalisation rate due to AECOPD was compared with a parallel period in the previous year. On average, patients were able to record 77% of their total study days. The system detected 73% of AECOPD. In further 27% of AECOPD patients sought treatment although the change in symptoms did not meet AECOPD definition. The number of COPD-related hospitalisations significantly reduced compared to the previous year. There was a significant increase in FEV(1) and FVC from the start to the end of the study. The remote monitoring device used in this study can be used in COPD patients. AECOPD was detected early in the majority of cases. Hospitalisation rate due to AECOPD was reduced and FEV(1) and FVC values increased during the study.
Remote daily monitoring of symptoms and spirometry had a poor uptake among CF patients. For those who completed the study, this method early detected P Exs that were treated with oral antibiotics that might otherwise required IV antibiotics.
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