Secondary metabolite from <em>Pseudomonas aeruginosa</em> LV strain exhibits antibacterial activity against <em>Staphylococcus aureus</em>

Abstract

This study aimed to evaluate the antibacterial activity of the dichloromethane/ethyl acetate fraction (named F4a), obtained from the culture of Pseudomonas aeruginosa LV strain in presence of copper chloride, against planktonic and sessile cells of Staphylococcus aureus, including those presenting multidrug resistance. First, the minimal inhibitory concentrations (MIC) of F4a for twenty-six clinical isolates were determined and the values ranged from 1.56 to 6.25 µg/mL. Minimal bactericidal concentration (MBC) of 3.13 µg/mL was detected in 84.6% of the isolates. The time-kill curve analysis revealed a significant decreased in colony-forming unit counts after 4 h of treatment with the MIC/MBC of F4a. Moreover, the MIC/MBC of the fluopsin C, a copper-containing compound present in F4a, were 1.56/3.13 µg/mL, indicating that this compound seems to be one of the active components related to the antibacterial activity against S. aureus. Images of transmission electron microscopy showed significant ultrastructural alterations in planktonic cells treated with the MIC/MBC of F4a. A significant reduction in the metabolic activity of established biofilms of all S. aureus isolates was observed after treatment with F4a. No hemolytic activity to human erythrocytes was detected for F4a, and the cytotoxic concentration to LLC-MK2 cells was 3.44 µg/mL. In conclusion, F4a exhibited a bactericidal activity against planktonic cells and inhibited the metabolic activity of biofilms of S. aureus. F4a can be promising for the development of new strategies for the treatment of infections caused by S. aureus.

Synergistic Antifungal Interaction between Pseudomonas aeruginosa LV Strain Metabolites and Biogenic Silver Nanoparticles against Candida auris

“…Previous studies have shown that the cytotoxic concentration of F4a and fluopsin C able to inhibit the viability of 50% (CC 50 ) of the LLC-MK2 cells (kidney epithelial cells from Macaca mulatta) was equal to 3.44 and 2.0 µg/mL, respectively, which was close to the MIC values determined for planktonic cells of C. auris in the present study. Moreover, at concentrations greater than 6.25 µg/mL of bacterial metabolites, no viable LLC-MK2 cells were detected [29,30]. In the present study, the CC 50 of indolin-3-one for LLC-MK2 cells was 71.69 µg/mL, and at the MIC value (100.0 µg/mL), approximately 42.0% of the cells were viable (data not shown).…”

“…The YC 73 also inhibited the growth of several fungal species, including one C. albicans isolate (MIC = 3.12 µg/mL) [31]. Regarding fluopsin C purified from P. aeruginosa LV strain, previous studies only reported the inhibition of planktonic cell growth of the multi-drug resistant bacteria, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-K. pneumoniae) [29,30].…”

“…Once inside the cell, AgNP can lead to increased intracellular reactive oxygen species (ROS) [56], and alterations in multiple targets such as cell wall integrity, membrane permeability and Studies on the mechanisms of action of F4a and fluopsin C, as well as AgNPs alone, have been described in the literature. Navarro et al [54] reported that the plasma membrane of Gram-positive and Gram-negative bacteria had been identified as the primary target of F4a and fluopsin C. The treatment of bacterial cells with these compounds affected the cell wall compaction, cell membrane permeabilization, and divisional septum and decreased the cytoplasmic electron density [29,30].…”

“…Kerbauy et al [28] reported a significant reduction in the biomass of 24-h biofilms of the bacterium KPC-K. pneumoniae, after treatment with the planktonic cells MIC value (62.5 µg/mL) of F3d (a dichloromethane fraction enriched with phenazine-1-carboxyamide and fluopsin C, and other minor components [23]). In addition, an antibiofilm activity was also observed in 24-h biofilms of Staphylococcus aureus, including those exhibiting methicillin-resistance, with F4a SMIC50 ranging from 12.5 to 25.0 µg/mL [30]. Next, the effects of F4a alone and combined with bioAgNP were evaluated on 24-h biofilms of C. auris strains.…”

“…These bacteria produce a wide range of secondary metabolites, some of which have a broad spectrum of antimicrobial activity, which may give them a selective advantage in natural environments [20,21]. Previous studies have shown that secondary metabolites from the culture of Pseudomonas aeruginosa LV strain, a bacterium isolated from a foliar lesion of Citrus sinensis var Valencia [22], have potent antibacterial activity against phytopathogens [23][24][25][26] and human multidrugresistant pathogens [27][28][29][30]. Secondary metabolites obtained from Pseudomonas spp.…”