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junio 4, 2021

Extreme Acid Modulates Fitness Tradeoffs of Multidrug Efflux Pumps MdtEF-TolC and AcrAB-TolC in <em>Escherichia coli</em> K-12

Bacterial genomes encode various multidrug efflux pumps (MDR) whose specific conditions for fitness advantage are unknown. We show that the efflux pump MdtEF-TolC, in Escherichia coli, confers a fitness advantage during exposure to extreme acid (pH 2). Our flow cytometry method revealed pH-dependent fitness tradeoffs between bile acids (a major pump substrate) and salicylic acid, a membrane-permeant aromatic acid that induces a drug-resistance regulon but depletes proton motive force (PMF). The…

Synergism between Rifampicin and Cationic Polyurethanes Overcomes Intrinsic Resistance of <em>Escherichia coli</em>

Antibiotic-resistant Gram-negative bacteria are emergent pathogens, causing millions of infections worldwide. While there are several classes of antibiotics that are effective against Gram-positive bacteria, the outer membrane (OM) of Gram-negative bacteria excludes high-molecular-weight hydrophobic antibiotics, making these species intrinsically resistant to several classes of antibiotics, including polyketides, aminocoumarins, and macrolides. The overuse of antibiotics such as β-lactams has…

Glutathione-Activated NO-/ROS-Generation Nanoparticles to Modulate the Tumor Hypoxic Microenvironment for Enhancing the Effect of HIFU-Combined Chemotherapy

The combination of high-intensity focused ultrasound (HIFU) and chemotherapy has promising potential in the synergistic treatment of various types of solid tumors. However, the clinical efficacy of HIFU in combination chemotherapy is often impeded by the pre-existing hypoxia tumor microenvironment-induced multidrug resistance (MDR). Therefore, it is imperative for HIFU combined with chemotherapy to overcome MDR by improving the tumor hypoxic microenvironment. Hence, we developed highly stable…

LncRNA DINOR is a virulence factor and global regulator of stress responses in Candida auris

The emergent fungal pathogen Candida auris exhibits high resistance to antifungal drugs and environmental stresses, impeding treatment and decontamination^(1-3). The fungal factors mediating this stress tolerance are largely unknown. In the present study, we performed piggyBac, transposon-mediated, genome-wide mutagenesis and genetic screening in C. auris, and identified a mutant that grew constitutively in the filamentous form. Mapping the transposon insertion site revealed the disruption of a…

Candidalysin triggers epithelial cellular stresses that induce necrotic death

Candida albicans is a common opportunistic fungal pathogen that causes a wide range of infections from superficial mucosal to hematogenously disseminated candidiasis. The hyphal form plays an important role in the pathogenic process by invading epithelial cells and causing tissue damage. Notably, the secretion of the hyphal toxin candidalysin is essential for both epithelial cell damage and activation of mucosal immune responses. However, the mechanism of candidalysin-induced cell death remains…

Candida esophagitis incidentally detected by 18F-FDG PET/CT in a patient with CNS lymphoma

Corticosteroids are commonly used in lymphoma patients, and findings in favor of esophageal involvement in 18F-FDG PET-CT should be considered suspicious and definitely be confirmed by biopsy. We describe a 58-year-old lady with diffuse large B-cell lymphoma and central nervous system involvement having an increased metabolism in the distal esophagus with 18F-FDG PET/CT, which was consistent with esophageal candidiasis, most probably due to prolonged use of dexamethasone. Esophageal candidiasis…