Bismuth-based drugs sensitize Pseudomonas aeruginosa to multiple antibiotics by disrupting iron homeostasis.

Pseudomonas aeruginosa infections are difficult to treat due to rapid development of antibiotic drug resistance. The synergistic combination of already-in-use drugs is an alternative to developing new antibiotics to combat antibiotic-resistant bacteria. Here we demonstrate that bismuth-based drugs (bismuth subsalicylate, colloidal bismuth subcitrate) in combination with different classes of antibiotics (tetracyclines, macrolides, quinolones, rifamycins and so on) can eliminate multidrug-resistant P.

Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance.

The rapid emergence of antimicrobial resistance (AMR) pathogens highlights the urgent need to approach this global burden with alternative strategies. Cefiderocol (Fetroja®) is a clinically-used sideromycin, that is utilized for the treatment of severe drug-resistant infections, caused by Gram-negative bacteria; there is evidence of cefiderocol-resistance occurring in bacterial strains however. To increase the efficacy and extend the life-span of sideromycins, we demonstrate strong synergisms between cefiderocol and metallodrugs (e.

Pseudomonas aeruginosa Citrate Synthase GltA Influences Antibiotic Tolerance and the Type III Secretion System through the Stringent Response.

Carbohydrate metabolism plays essential roles in energy generation and providing carbon skeletons for amino acid syntheses. In addition, carbohydrate metabolism has been shown to influence bacterial susceptibility to antibiotics and virulence. In this study, we demonstrate that citrate synthase mutation can increase the expression of the type III secretion system (T3SS) genes and antibiotic tolerance in Pseudomonas aeruginosa.

A prognostic nomogram to predict survival in elderly patients with small-cell lung cancer: a large population-based cohort study and external validation.

Background: Age is an independent prognostic factor for small cell lung cancer (SCLC). We aimed to construct a nomogram survival prediction for elderly SCLC patients based on the Surveillance, Epidemiology, and End Results (SEER) database.

Methods: A total of 2851 elderly SCLC patients from the SEER database were selected as a primary cohort, which were randomly divided into a training cohort and an internal validation cohort.

Dihydrolipoamide Acetyltransferase AceF Influences the Type III Secretion System and Resistance to Oxidative Stresses through RsmY/Z in .

Carbon metabolism plays an important role in bacterial physiology and pathogenesis. The type III secretion system (T3SS) of is a virulence factor that contributes to acute infections. It has been demonstrated that bacterial metabolism affects the T3SS.

RplI interacts with 5' UTR of exsA to repress its translation and type III secretion system in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an important opportunistic pathogen capable of causing variety of infections in humans. The type III secretion system (T3SS) is a critical virulence determinant of P. aeruginosa in the host infections.

The cathelicidin-derived close-to-nature peptide D-11 sensitises Klebsiella pneumoniae to a range of antibiotics in vitro, ex vivo and in vivo.

The outer membrane of Gram-negative bacteria constitutes a permeability barrier that prevents certain antibiotics reaching their target, thus conferring a high tolerance to a wide range of antibiotics. Combined therapies of antibiotics and outer membrane-perturbing drugs have been proposed as an alternative treatment to extend the use of antibiotics active against Gram-positive bacteria to Gram-negative bacteria. Among the outer membrane-active compounds, the outer membrane-permeabilising peptides play a prominent role.

Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics.

The emergence and rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to the global healthcare. There is an urgent need for new antibacterial substances or new treatment strategies to deal with the infections by MDR bacterial pathogens, especially the Gram-negative pathogens. In this study, we show that a number of synthetic cationic peptides display strong synergistic antimicrobial effects with multiple antibiotics against the Gram-negative pathogen Pseudomonas aeruginosa.

Establishment and Verification of a Nomogram for Predicting Survival in Patients with Small Intestinal Gastrointestinal Stromal Tumors.

Background: This study aimed to develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in small intestinal gastrointestinal stromal tumors (SI GISTs).

Methods: Patients diagnosed with SI GISTs were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and further randomly divided into training and validating cohorts. Univariate and multivariate Cox analyses were conducted in the training set to determine independent prognostic factors to build nomograms for predicting 3- and 5-year OS and CSS.

YbeY controls the type III and type VI secretion systems and biofilm formation through RetS in .

YbeY is a highly conserved RNase in bacteria and plays essential roles in the maturation of 16S rRNA, regulation of small RNAs (sRNAs) and bacterial responses to environmental stresses. Previously, we verified the role of YbeY in rRNA processing and ribosome maturation in and demonstrated YbeY-mediated regulation of through a sRNA ReaL. In this study, we demonstrate that mutation of the gene results in upregulation of the type III secretion system (T3SS) genes as well as downregulation of the type VI secretion system (T6SS) genes and reduction of biofilm formation.

Endoribonuclease YbeY Is Essential for RNA Processing and Virulence in Pseudomonas aeruginosa.

Posttranscriptional regulation plays an essential role in the quick adaptation of pathogenic bacteria to host environments, and RNases play key roles in this process by modifying small RNAs and mRNAs. We find that the endonuclease YbeY is required for rRNA processing and the bacterial virulence in a murine acute pneumonia model. Transcriptomic analyses reveal that knocking out the gene results in downregulation of oxidative stress response genes, including the catalase genes and Consistently, the mutant is more susceptible to HO and neutrophil-mediated killing.

TpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in Pseudomonas aeruginosa.

Carbon metabolism plays an essential role in bacterial pathogenesis and susceptibility to antibiotics. In , Crc, Hfq, and a small RNA, CrcZ, are central regulators of carbon metabolism. By screening mutants of genes involved in carbon metabolism, we found that mutation of the gene reduces the expression of the type III secretion system (T3SS) and bacterial resistance to aminoglycoside antibiotics.

Identification of novel genes that promote persister formation by repressing transcription and cell division in Pseudomonas aeruginosa.

Objectives: Bacterial persisters are a small subpopulation of cells that are highly tolerant of antibiotics and contribute to chronic and recalcitrant infections. Global gene expression in Pseudomonas aeruginosa persister cells and genes contributing to persister formation remain largely unknown. The objective of this study was to examine the gene expression profiles of the persister cells and those that regained growth in fresh medium, as well as to identify novel genes related to persister formation.

Identification of a small RNA that directly controls the translation of the quorum sensing signal synthase gene rhlI in Pseudomonas aeruginosa.

The biofilm formation by Pseudomonas aeruginosa highly increases the bacterial resistance to antimicrobial agents and host immune clearance. The biofilm formation is positively regulated by two small RNAs, RsmY and RsmZ. Previously, we reported that mutation in the polynucleotide phosphorylase (PNPase) coding gene pnp increases the levels of RsmY/Z.

Oligoribonuclease Contributes to Tolerance to Aminoglycoside and β-Lactam Antibiotics by Regulating KatA in Pseudomonas aeruginosa.

is an opportunistic bacterial pathogen and is intrinsically resistant to a variety of antibiotics. Oligoribonuclease (Orn) is a 3'-to-5' exonuclease that degrades nanoRNAs. The Orn controls biofilm formation by influencing the homeostasis of cyclic-di-GMP.