Phenazines as potential biomarkers of Pseudomonas aeruginosa infections: synthesis regulation, pathogenesis and analytical methods for their detection

Vilaplana, Lluı̈sa; Marco, Marı́a Pilar

doi:10.1007/s00216-020-02696-4

Cited by 33 publications

(36 citation statements)

References 119 publications

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“…Therefore, it is essential to have appropriate diagnostic strategies to detect infections at early stages (acute infections). This early detection will allow applying more specific antibiotic treatments, preventing chronification of the infections and the appearance of resistant strains ( Vilaplana and Marco, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Diagnosis and Stratification of Pseudomonas aeruginosa Infected Patients by Immunochemical Quantitative Determination of Pyocyanin From Clinical Bacterial Isolates

Rodriguez-Urretavizcaya

Pascual

Pastells

et al. 2021

Front. Cell. Infect. Microbiol.

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The development of a highly sensitive, specific, and reliable immunochemical assay to detect pyocyanin (PYO), one of the most important virulence factors (VFs) of Pseudomonas aeruginosa, is here reported. The assay uses a high-affinity monoclonal antibody (mAb; C.9.1.9.1.1.2.2.) raised against 1-hydroxyphenazine (1-OHphz) hapten derivatives (PC1; a 1:1 mixture of 9-hydroxy- and 6-hydroxy-phenazine-2-carobxylic acids). Selective screening using PYO and 1-OHphz on several cloning cycles allowed the selection of a clone able to detect PYO at low concentration levels. The microplate-based ELISA developed is able to achieve a limit of detection (LoD) of 0.07 nM, which is much lower than the concentrations reported to be found in clinical samples (130 μM in sputa and 2.8 μM in ear secretions). The ELISA has allowed the investigation of the release kinetics of PYO and 1-OHphz (the main metabolite of PYO) of clinical isolates obtained from P. aeruginosa-infected patients and cultured in Mueller–Hinton medium. Significant differences have been found between clinical isolates obtained from patients with an acute or a chronic infection (~6,000 nM vs. ~8 nM of PYO content, respectively) corroborated by the analysis of PYO/1-OHphz levels released by 37 clinical isolates obtained from infected patients at different stages. In all cases, the levels of 1-OHphz were much lower than those of PYO (at the highest levels 6,000 nM vs. 300 nM for PYO vs. 1-OHphz, respectively). The results found point to a real potential of PYO as a biomarker of P. aeruginosa infection and the possibility to use such VF also as a biomarker for patient stratification[2] and for an effective management of these kinds of infections.

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Section: Discussionmentioning

confidence: 99%

Diagnosis and Stratification of Pseudomonas aeruginosa Infected Patients by Immunochemical Quantitative Determination of Pyocyanin From Clinical Bacterial Isolates

Rodriguez-Urretavizcaya

Pascual

Pastells

et al. 2021

Front. Cell. Infect. Microbiol.

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“…However, all strains were found as phenotypically sensitive to colistin. Both XDR strains were involved in chronic respiratory system infections as P. aeruginosa is the main pathogen with a role in chronic respiratory infections and pulmonary complications [20].…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Resistance and Genomic Characterization of Six New Sequence Types in Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates from Pakistan

et al. 2021

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Pseudomonas aeruginosa (P. aeruginosa) is a major bacterial pathogen associated with a variety of infections with high mortality rates. Most of the clinical P. aeruginosa isolates belong to a limited number of genetic subgroups characterized by multiple housekeeping genes’ sequences (usually 5–7) through the Multi-Locus Sequence Typing (MLST) scheme. The emergence and dissemination of novel multidrug-resistant (MDR) sequence types (ST) in P. aeruginosa pose serious clinical concerns. We performed whole-genome sequencing on a cohort (n = 160) of MDR P. aeruginosa isolates collected from a tertiary care hospital lab in Pakistan and found six isolates belonging to six unique MLST allelic profiles. The genomes were submitted to the PubMLST database and new ST numbers (ST3493, ST3494, ST3472, ST3489, ST3491, and ST3492) were assigned to the respective allele combinations. MLST and core-genome-based phylogenetic analysis confirmed the divergence of these isolates and positioned them in separate branches. Analysis of the resistome of the new STs isolates revealed the presence of genes blaOXA-50, blaPAO, blaPDC, blaVIM-2, aph(3′)-IIb, aac(6′)-II, aac(3)-Id, fosA, catB7, dfrB2, crpP, merP and a number of missense and frame-shift mutations in chromosomal genes conferring resistance to various antipseudomonal antibiotics. The exoS, exoT, pvdE, rhlI, rhlR, lasA, lasB, lasI, and lasR genes were the most prevalent virulence-related genes among the new ST isolates. The different genotypic features revealed the adaptation of these new clones to a variety of infections by various mutations in genes affecting antimicrobial resistance, quorum sensing and biofilm formation. Close monitoring of these antibiotic-resistant pathogens and surveillance mechanisms needs to be adopted to reduce their spread to the healthcare facilities of Pakistan. We believe that these strains can be used as reference strains for future comparative analysis of isolates belonging to the same STs.

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“…This species is ubiquitous in nature and has been found inhabiting soil and water, and colonizing humans, sometimes acting as an opportunistic pathogen (1). In immunosuppressed, burnt, and hospitalized patients, P. aeruginosa is responsible for a broad spectrum of serious diseases ranging from acute to chronic infections, such as bloodstream infections in intensive care units (ICU), surgical site infections, hospital-acquired pneumonia, respiratory and urinary tract infections, and burn and chronic dermal wound infections (1, 2). P. aeruginosa also chronically infects the lungs of people with underlying pulmonary diseases, as cystic fibrosis (CF).…”

Section: Introductionmentioning

confidence: 99%

“…Phenazines are nitrogen-containing colored aromatic molecules, which constitute a large group of secondary metabolites (SM) produced by bacteria with broad physiological functions, acting as antibiotics (2) and antifungals (24, 25, 26, 27), involved in biofilm formation (28), and regulation of gene expression (29). Several phenazines are produced by P. aeruginosa , such as pyocyanin (PYO); phenazine-1-carboxamide (PCN); phenazine-1-carboxylic acid (PCA); 1-hydroxyphenazine (1-OHphz), and 5-methyl-phenazine-1-carboxylic acid (5-Me-PCA).…”

Section: Introductionmentioning

confidence: 99%

Secondary metabolites produced during Aspergillus fumigatus and Pseudomonas aeruginosa biofilm formation

Bastos

Akiyama

Reis

et al. 2022

Preprint

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In Cystic Fibrosis (CF), mucus plaques are formed in the patient’s lung, creating a hypoxic condition and a propitious environment for colonization and persistence of many microorganisms. There is clinical evidence showing that Aspergillus fumigatus can co-colonize CF patients with Pseudomonas aeruginosa, which has been associated with lung function decline. P. aeruginosa produces several compounds with inhibitory and anti-biofilm effects against A. fumigatus in vitro; however, little is known about the fungal compounds produced in counterattack. Here, we annotated fungal and bacterial secondary metabolites (SM) produced in mixed biofilms in normoxia and hypoxia conditions. We detected nine SMs produced by P. aeruginosa. Phenazines and different analogs of pyoverdin were the main compounds produced by P. aeruginosa, and their secretion were increased by the fungal presence. The roles of the two operons responsible for phenazines production (phzA1 and phzA2) were also investigated showing both mutants are able to produce partial sets of phenazines. We detected a total of 20 SMs secreted by A. fumigatus either in monoculture or in co-culture with P. aeruginosa. All these compounds are secreted during biofilm formation either in normoxia or hypoxia. However, only eight compounds (demethoxyfumitremorgin C, fumitremorgin, ferrichrome, ferricrocin, tricetylfusigen, gliotoxin, gliotoxin E, and pyripyropene A) were detected during the biofilm formation by the co-culture of A. fumigatus and P. aeruginosa upon both normoxia and hypoxia conditions. Overall, we showed how diverse is SM secretion during A. fumigatus and P. aeruginosa mixed culture and how this can affect biofilm formation both in normoxia and hypoxia.Author SummaryThe interaction between Pseudomonas aeruginosa and Aspergillus fumigatus has been well-characterized in vitro. In this scenario, the bacterium exerts a strong inhibitory effect against the fungus. However, little is known about the metabolites produced by the fungus to counterattack the bacteria. Our work aimed to annotate secondary metabolites (SM) secreted during co-culture between P. aeruginosa and A. fumigatus during biofilm formation in both normoxia and hypoxia. The bacterium produces several different types of phenazines and pyoverdins, in response to the fungus presence. In contrast, we were able to annotate 29 metabolites produced during A. fumigatus biofilm formation but only eight compounds were detected during biofilm formation by the co-culture of A. fumigatus and P. aeruginosa upon both normoxia and hypoxia. In conclusion, we have detected many SMs secreted during A. fumigatus and P. aeruginosa biofilm formation. This analysis can provide several opportunities to understand the interaction between these two species.

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Phenazines as potential biomarkers of Pseudomonas aeruginosa infections: synthesis regulation, pathogenesis and analytical methods for their detection

Cited by 33 publications

References 119 publications

Diagnosis and Stratification of Pseudomonas aeruginosa Infected Patients by Immunochemical Quantitative Determination of Pyocyanin From Clinical Bacterial Isolates

Diagnosis and Stratification of Pseudomonas aeruginosa Infected Patients by Immunochemical Quantitative Determination of Pyocyanin From Clinical Bacterial Isolates

Antimicrobial Resistance and Genomic Characterization of Six New Sequence Types in Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates from Pakistan

Secondary metabolites produced during Aspergillus fumigatus and Pseudomonas aeruginosa biofilm formation

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