New Insights about Antibiotic Production by Pseudomonas aeruginosa: A Gene Expression Analysis

Abstract

The bacterial resistance for antibiotics is one of the most important problems in public health and only a small number of new products are in development. Antagonistic microorganisms from soil are a promising source of new candidate molecules. Products of secondary metabolism confer adaptive advantages for their producer, in the competition for nutrients in the microbial community. The biosynthesis process of compounds with antibiotic activity is the key to optimize their production and the transcriptomic study of microorganisms is of great benefit for the discovery of these metabolic pathways. Pseudomonas aeruginosa LV strain growing in the presence of copper chloride produces a bioactive organometallic compound, which has a potent antimicrobial activity against various microorganisms. The objective of this study was to verify overexpressed genes and evaluate their relation to the organometallic biosynthesis in this microorganism. P. aeruginosa LV strain was cultured in presence and absence of copper chloride. Two methods were used for transcriptomic analysis, genome reference-guided assembly and de novo assembly. The genome referenced analysis identified nine upregulated genes when bacteria were exposed to copper chloride, while the De Novo Assembly identified 12 upregulated genes. Nineteen genes can be related to an increased microbial metabolism for the extrusion process of exceeding intracellular copper. Two important genes are related to the biosynthesis of phenazine and tetrapyrroles compounds, which can be involved in the bioremediation of intracellular copper and we suggesting that may involve in the biosynthesis of the organometallic compound. Additional studies are being carried out to further prove the function of the described genes and relate them to the biosynthetic pathway of the organometallic compound.

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

“…The Fluopsin C was produced by P. aeruginosa LV strain (GenBank: QBLE00000000.1). These microorganisms were isolated from a citrus canker lesion on an orange ( Citrus sinensis cv.Valence) at Astorga, Paraná, Brazil (Gionco et al, 2017). The pathogens K. pneumoniae ATCC 10031 and Enterococcus faecium ATCC 6569 were used as susceptible strains.…”

“…Indeed, our research group demonstrated the strong antibiotic activity of these semi-purified fractions against planktonic cells and biofilm formation of MDR isolates (Kerbauy et al, 2016). The gene expression analysis of P. aeruginosa LV strain showed that, when it is cultured in the presence of copper chloride, the bioremediation of intracellular excess copper forms a compound with high antimicrobial activity (Gionco et al, 2017). This bioactive compound was identified as a metalloantibiotic (organocopper compound), which is a great candidate for the development of new antibiotics to control infections caused by MRSA, CRE, VRE, and KPC-producing strains (Cardozo et al, 2013; Kerbauy et al, 2016).…”

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

“…The development of metalloantibiotics as potential antimicrobial agents has been pursued since the 90s (Sekhon, 2010). The gene expression analysis of Pseudomonas aeruginosa LV strain cultured in the presence of copper chloride suggested that the intracellular excess of copper forms a compound with antimicrobial activity (Gionco et al, 2017). Other studies demonstrated that a specific fraction extracted from the supernatant of P. aeruginosa LV strain culture (F4A) presents high microbicidal activity against many pathogenic bacteria (de Oliveira et al, 2011Oliveira et al, , 2016Cardozo et al, 2013;Murate et al, 2015;Kerbauy et al, 2016;Munhoz et al, 2017).…”

Growth inhibition of pathogenic microorganisms by Pseudomonas protegens EMM-1 and partial characterization of inhibitory substances

“…protegens EMM-1 revealed an estimated molecular mass of 3 to 10 kDa. Although we cannot exclude the possibility that other inhibitory substances can be obtained by other methodologies as reported in other Pseudomonas species [ 54 , 55 ]. The inhibitory activity remained active at low pH and was not affected by heat treatment.…”