Secondary Metabolites of Pseudomonas aeruginosa LV Strain Decrease Asian Soybean Rust Severity in Experimentally Infected Plants.

Asian Soybean Rust (ASR), a disease caused by Phakopsora pachyrhizi, causing yield losses up to 90%. The control is based on the fungicides which may generate resistant fungi. The activation of the plant defense system, should help on ASR control. In this study, secondary metabolites of Pseudomonas aeruginosa LV strain were applied on spore germination and the expression of defense genes in infected soybean plants. The F4A fraction and the pure metabolites were used. In vitro, 10 µg mL-1 of F4A reduced spore germination by 54%, while 100 µg mL-1 completely inhibited. Overexpression of phenylalanine ammonia lyase (PAL), O-methyltransferase (OMT) and pathogenesis related protein-2 (PR-2; glucanases) defense-related genes were detected 24 and 72 h after soybean sprouts were sprayed with an organocopper antimicrobial compound (OAC). Under greenhouse conditions, the best control was observed in plants treated with 60 µg mL-1 of PCA, which reduced ASR severity and lesion frequency by 75% and 43%, respectively. Plants sprayed with 2 and 20 µg mL-1 of F4A also decreased severity (41%) and lesion frequency (32%). The significant reduction in spore germination ASR in plant suggested that the strain of these metabolites are effective against P. pachyrhizi, and they can be used for ASR control.

Corrigendum: Determining the Targets of Fluopsin C Action on Gram-Negative and Gram-Positive Bacteria.

[This corrects the article DOI: 10.3389/fmicb.2020.01076.].

Determining the Targets of Fluopsin C Action on Gram-Negative and Gram-Positive Bacteria.

The antibiotic activity of metalloantibiotic compounds has been evaluated since the 90s, and many different modes of action were characterized. In the last decade, the effects of secondary metabolites produced by Pseudomonas aeruginosa LV strain, including a cupric compound identified as Fluopsin C, were tested against many pathogenic bacteria strains, proving their high antibiotic activity. In the present study, the bactericidal mechanisms of action of Fluopsin C and the semi-purified fraction F4A were elucidated. The results found in electron microscopy [scanning electron microscopy (SEM) and transmission electronic microscopy (TEM)] demonstrated that both Fluopsin C and F4A are affecting the cytoplasmatic membrane of Gram-positive and Gram-negative bacteria. These results were confirmed by fluorescence microscopy, where these bacteria presented permeabilization of their cytoplasmatic membranes after contact with the semi-purified fraction and pure compound. Using electronic and fluorescence microscopy, along with bacterial mutant strains with marked divisional septum, the membrane was defined as the primary target of Fluopsin C in the tested bacteria.

Fluopsin C for Treating Multidrug-Resistant Infections: In vitro Activity Against Clinically Important Strains and in vivo Efficacy Against Carbapenemase-Producing Klebsiella pneumoniae.

The increasing emergence of multidrug-resistant (MDR) organisms in hospital infections is causing a global public health crisis. The development of drugs with effective antibiotic action against such agents is of the highest priority. In the present study, the action of Fluopsin C against MDR clinical isolates was evaluated under in vitro and in vivo conditions. Fluopsin C was produced in cell suspension culture of Pseudomonas aeruginosa LV strain, purified by liquid adsorption chromatography and identified by mass spectrometric analysis. Bioactivity, bacterial resistance development risk against clinically important pathogenic strains and toxicity in mammalian cell were initially determined by in vitro models. In vivo toxicity was evaluated in Tenebrio molitor larvae and mice. The therapeutic efficacy of intravenous Fluopsin C administration was evaluated in a murine model of Klebsiella pneumoniae (KPC) acute sepsis, using six different treatments. The in vitro results indicated MIC and MBC below 2 µg/mL and low bacterial resistance development frequency. Electron microscopy showed that Fluopsin C may have altered the exopolysaccharide matrix and caused disruption of the cell wall of MDR bacteria. Best therapeutic results were achieved in mice treated with a single dose of 2 mg/kg and in mice treated with two doses of 1 mg/kg, 8 h apart. Furthermore, acute and chronic histopathological studies demonstrated absent nephrotoxicity and moderate hepatotoxicity. The results demonstrated the efficacy of Fluopsin C against MDR organisms in in vitro and in vivo models, and hence it can be a novel therapeutic agent for the control of severe MDR infections.