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PneumoPhageColor - development of a colorimetric biodetection kit for Pseudomonas aeruginosa based on phage particles

Abstract

Infectious diseases kill between 17-20 million people a year worldwide, and about 10 million people acquire hospital infections (HI) and, from this universe, almost 300,000 die. HIs increase both the length of permanence in the hospital and treatment costs, besides contributing significantly to the morbidity and mortality in hospitalized patients. In Brazil, the exact prevalence of HIs is still unknown, however, a national survey conducted by the Ministry of Health revealed, among several institutions evaluated, a rate of nosocomial infections ranging from 13% to 15%. The rate of HIs in Brazil presents high values and is considered almost the double when compared to other countries. Thus, hospital acquired infections represents a major challenge to be faced by the government and society for the implementation of prevention and control of infection in hospitals. Among the microorganisms that cause HIs one can highlight the multidrug-resistant Pseudomonas aeruginosa, which represents a major threat to patients in health care services. Data from 2007 points to P. aeruginosa as the most frequently isolated pathogen in patients with nosocomial pneumonia, a common cause of urinary tract infections, surgical wound and burn infections, being also present in bloodstream infections. The bacterium P. aeruginosa has been highlighted in the social media in Brazil about seven years ago, following the death of the 20 year-old model Mariana Bridi, on January 24th 2009, at Dorio Silva Hospital in the city of Serra (ES). According to a spokesperson of the state government, the death was due to complications from a generalized serious infection, originated from a urinary tract infection. In recent years, nosocomial infections caused by multiresistant Gram-negative microorganisms has increased consistently in Brazilian hospitals, and the bacterium P. aeruginosa was responsible for 10% of all nosocomial infections. It is intended that PneumoPhageColor will be a rapid detection (> 2 hours <5h) and low-cost kit for the high precision biodetection of P. aeruginosa, based on the use of a hydrogel sensitive to color changes, fixed on a support material, containing phage particles (or a cocktail of phage particles) specific and strictly lytic against P. aeruginosa. The proposed concept is not new, existing from about 3.5 billion years, having been initiated when bacteria and bacteriophages established a predator-prey balance. Bacteriophages are the most abundant organisms on our planet (are estimated at more than 10^31 particles) being completely safe for all organisms including humans, except for their target bacterial hosts. The idea embodied in PneumoPhageColor is unconventional and a highly creative approach, since it will join the solution (phage) with the problem (bacteria) in order to detect the latter. One intends to establish the proof-of-concept using a bacteriophage and a collection strain of P. aeruginosa. This research project will investigate the potential for the structural and functional stabilization of a lytic phage (or cocktail of lytic phage particles) with broad-spectrum, capable of infecting P. aeruginosa, within a hydrogel with chromogenic characteristics. Specific reagents will be incorporated into the optimized hydrogel in varying concentrations, in order to produce signal (color) if it is present in the gel a certain intracytoplasmic enzyme, released by phage lysis should bacterial cells of P. aeruginosa become into contact with the hydrogel. The intensity of the color produced in the hydrogel will give an idea of the bacterial load present, and this intensity will be measured by an optical sensor coupled to a signal transducer. (AU)

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Scientific publications (25)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SILVA, ERICA C.; OLIVEIRA, THAIS J.; MORELI, FERNANDA C.; HARADA, LILIAM K.; VILA, MARTA M. D. C.; BALCAO, VICTOR M.. Newly isolated lytic bacteriophages for Staphylococcus intermedius, structurally and functionally stabilized in a hydroxyethylcellulose gel containing choline geranate: Potential for transdermal permeation in veterinary phage therapy. Research in Veterinary Science, v. 135, p. 42-58, . (16/12234-4, 16/08884-3, 18/05522-9)
HERNANDES, AUDREY N.; BOSCARIOL, RODRIGO; BALCAO, VICTOR M.; VILA, MARTA M. D. C.. Transdermal Permeation of Caffeine Aided by Ionic Liquids: Potential for Enhanced Treatment of Cellulitis. AAPS PHARMSCITECH, v. 22, n. 3, . (18/05522-9, 16/12234-4, 16/08884-3)
BOSCARIOL, RODRIGO; CAETANO, ERIKA A.; SILVA, ERICA C.; OLIVEIRA, THAIS J.; ROSA-CASTRO, RAQUEL M.; VILA, MARTA M. D. C.; BALCAO, VICTOR M.. Performance of Choline Geranate Deep Eutectic Solvent as Transdermal Permeation Enhancer: An In Vitro Skin Histological Study. PHARMACEUTICS, v. 13, n. 4, . (16/12234-4, 16/08884-3, 18/05522-9)
HARADA, LILIAM K.; JUNIOR, WALDEMAR BONVENTI; SILVA, ERICA C.; OLIVEIRA, THAIS J.; MORELI, FERNANDA C.; JUNIOR, JOSE M. OLIVEIRA; TUBINO, MATTHIEU; VILA, MARTA M. D. C.; BALCAO, VICTOR M.. Bacteriophage-Based Biosensing of Pseudomonas aeruginosa: An Integrated Approach for the Putative Real-Time Detection of Multi-Drug-Resistant Strains. BIOSENSORS-BASEL, v. 11, n. 4, . (16/08884-3, 16/12234-4, 18/05522-9)
CAMPOS, WELIDA F.; SILVA, ERICA C.; OLIVEIRA, THAIS J.; OLIVEIRA, JR., JOSE M.; TUBINO, MATTHIEU; PEREIRA, CARLA; VILA, MARTA M. D. C.; BALCAO, VICTOR M.. Transdermal permeation of bacteriophage particles by choline oleate: potential for treatment of soft-tissue infections. FUTURE MICROBIOLOGY, v. 15, n. 10, p. 881-896, . (16/08884-3, 18/05522-9, 16/12234-4)
LIMA, RENATA; DEL FIOL, FERNANDO SA; BALCAO, VICTOR M.. Prospects for the Use of New Technologies to Combat Multidrug-Resistant Bacteria. FRONTIERS IN PHARMACOLOGY, v. 10, . (16/12234-4, 17/13328-5, 16/08884-3, 18/05522-9)
FABIANA CRISTINA ROSA MITELMÃO; SALVADOR MANGINI FILHO; MARCO VINÍCIUS CHAUD; MARTA MARIA DUARTE CARVALHO VILA; VICTOR MANUEL CARDOSO FIGUEIREDO BALCÃO; JOSÉ MARTINS DE OLIVEIRA JUNIOR. Caracterização física de Cateteres Centrais de Inserção Periférica (CCIP). MATERIA-RIO DE JANEIRO, v. 25, n. 1, . (18/05522-9, 13/03181-6, 12/15651-4, 16/08884-3)
FAVARO, LAURA I. L.; BALCAO, VICTOR M.; ROCHA, LILIAM K. H.; SILVA, ERICA C.; OLIVEIRA JR, JOSE M.; VILA, MARTA M. D. C.; TUBINO, MATTHIEU. Physicochemical Characterization of a Crude Anthocyanin Extract from the Fruits of Jussara (Euterpe edulis Martius): Potential for Food and Pharmaceutical Applications. Journal of the Brazilian Chemical Society, v. 29, n. 10, p. 2072-2088, . (16/16641-3, 16/12234-4, 16/08884-3)
LILIAN VIEIRA VAZ; VICTOR MANUEL BALCÃO; JOSÉ MARTINS OLIVEIRA JR; MATTHIEU TUBINO; ANGELA JOZALA; VALQUÍRIA MIWA HANAI YOSHIDA; MARTA MARIA DUARTE CARVALHO VILA. Development and Characterization of a Hydrogel Containing Silver Sulfadiazine for Antimicrobial Topical Applications. Part II: Stability, Cytotoxicity and Silver Release Patterns. Brazilian Journal of Pharmaceutical Sciences, v. 58, . (16/12234-4, 18/05522-9, 16/08884-3)
RIOS, ALESSANDRA C.; VILA, MARTA M. D. C.; LIMA, RENATA; DEL FIOL, FERNANDO S.; TUBINO, MATTHIEU; TEIXEIRA, JOSE A.; BALCAO, VICTOR M.. Structural and functional stabilization of bacteriophage particles within the aqueous core of a W/O/W multiple emulsion: A potential biotherapeutic system for the inhalational treatment of bacterial pneumonia. Process Biochemistry, v. 64, p. 177-192, . (13/03181-6, 16/08884-3, 16/12234-4)
JORGE, LUDMILLA R.; HARADA, LILIAM K.; SILVA, ERICA C.; CAMPOS, WELIDA F.; MORELLI, FERNANDA C.; SHIMAMOTO, GUSTAVO; PEREIRA, JORGE F. B.; OLIVEIRA JR, JOSE M.; TUBINO, MATTHIEU; VILA, MARTA M. D. C.; et al. Non-invasive Transdermal Delivery of Human Insulin Using Ionic Liquids: In vitro Studies. FRONTIERS IN PHARMACOLOGY, v. 11, . (16/08884-3, 18/05522-9, 16/12234-4)
LUDMILLA R. JORGE; LILIAM K. HARADA; ERICA C. SILVA; WELIDA F. CAMPOS; JOSÉ M. OLIVEIRA JR.; MARTA M. D. C. VILA; MATTHIEU TUBINO; VICTOR M. BALCÃO. BACTERIAL NANOCELLULOSE BIOMEMBRANE AS A SUPPORT FOR HUMAN INSULIN AIMING AT TRANSDERMAL PERMEATION. Química Nova, v. 43, n. 5, p. 572-578, . (16/12234-4, 18/05522-9, 16/16641-3, 16/08884-3)
ROCHA, LILIAM K. H.; FAVARO, LAURA I. L.; RIOS, ALESSANDRA C.; SILVA, ERICA C.; SILVA, WELIDA F.; STIGLIANI, TATIANE P.; GUNGER, MARIANA; LIMA, RENATA; OLIVEIRA, JR., JOSE M.; ARANHA, NORBERTO; et al. Sericin from Bombyx mori cocoons. Part I: Extraction and physicochemical-biological characterization for biopharmaceutical applications. Process Biochemistry, v. 61, p. 163-177, . (16/16641-3, 16/12234-4, 16/08884-3)
BALCAO, VICTOR M.; BELLINE, BIANCA G.; SILVA, ERICA C.; ALMEIDA, PABLO F. F. B.; BALDO, DENICEZAR A.; AMORIM, LARA R. P.; OLIVEIRA JUNIOR, JOSE M.; VILA, MARTA M. D. C.; DEL FIOL, FERNANDO S.. Isolation and Molecular Characterization of Two Novel Lytic Bacteriophages for the Biocontrol of Escherichia coli in Uterine Infections: In Vitro and Ex Vivo Preliminary Studies in Veterinary Medicine. PHARMACEUTICS, v. 14, n. 11, p. 40-pg., . (16/12234-4, 21/11716-3, 16/08884-3, 18/05522-9)
VILA, MARTA M. D. C.; BOSCARIOL, RODRIGO; BALCAO, VICTOR M.. NANOSTRUCTURED CURCUMIN WITH CHOLINE AND GERANIC ACID IONIC LIQUID (CAGE-IL): POTENTIAL FOR INCORPORATION INTO PHARMACEUTICAL GEL FORMULATIONS. Química Nova, v. N/A, p. 7-pg., . (16/12234-4, 16/08884-3, 18/05522-9)
HARADA, LILIAM K.; SILVA, ERICA C.; ROSSI, FERNANDO P. N.; CIEZA, BASILIO; OLIVEIRA, THAIS J.; PEREIRA, CARLA; TOMAZETTO, GEIZECLER; SILVA, BIANCA B.; SQUINA, FABIO M.; VILA, MARTA M. D. C.; et al. Characterization and in vitro testing of newly isolated lytic bacteriophages for the biocontrol of Pseudomonas aeruginosa. FUTURE MICROBIOLOGY, v. 17, n. 2, p. 111-141, . (18/05522-9, 16/12234-4, 16/08884-3)
BOSCARIOL, RODRIGO; OLIVEIRA JUNIOR, JOSE M.; BALDO, DENICEZAR A.; BALCAO, VICTOR M.; VILA, MARTA M. D. C.. Transdermal permeation of curcumin promoted by choline geranate ionic liquid: Potential for the treatment of skin diseases. SAUDI PHARMACEUTICAL JOURNAL, v. 30, n. 4, p. 16-pg., . (16/12234-4, 18/05522-9, 16/08884-3)
BOSCARIOL, RODRIGO; CAETANO, ERIKA A.; GROTTO, DENISE; ROSA-CASTRO, RAQUEL M.; OLIVEIRA JUNIOR, JOSE M.; VILA, MARTA M. D. C.; BALCAO, VICTOR M.. Transdermal Permeation Assays of Curcumin Aided by CAGE-IL: In Vivo Control of Psoriasis. PHARMACEUTICS, v. 14, n. 4, p. 21-pg., . (16/12234-4, 16/08884-3, 18/05522-9)
BALCAO, VICTOR M.; HARADA, LILIAM K.; JORGE, LUDMILLA R.; OLIVEIRA JR, JOSE M.; TUBINO, MATTHIEU; VILA, MARTA M. D. C.. Structural and Functional Stabilization of Sericin from Bombyx mori Cocoons in a Biopolysaccharide Film: Bioorigami for Skin Regeneration. Journal of the Brazilian Chemical Society, v. 31, n. 4, p. 833-848, . (16/16641-3, 18/05522-9, 16/12234-4, 16/08884-3)
BALCAO, VICTOR M.; BASU, AAKASH; CIEZA, BASILIO; ROSSI, FERNANDO N.; PEREIRA, CARLA; VILA, MARTA M. D. C.; SETUBAL, JOAO C.; HA, TAEKJIP; DA SILVA, ALINE M.. Pseudomonas-tailed lytic phages: genome mechanical analysis and putative correlation with virion morphogenesis yield. FUTURE MICROBIOLOGY, v. 17, n. 13, p. 18-pg., . (16/08884-3, 18/05522-9, 16/12234-4)
BALCAO, VICTOR M.; MORELI, FERNANDA C.; SILVA, ERICA C.; BELLINE, BIANCA G.; MARTINS, LAYLA F.; ROSSI, FERNANDO P. N.; PEREIRA, CARLA; VILA, MARTA M. D. C.; DA SILVA, ALINE M.. Isolation and Molecular Characterization of a Novel Lytic Bacteriophage That Inactivates MDR Klebsiella pneumoniae Strains. PHARMACEUTICS, v. 14, n. 7, p. 21-pg., . (16/08884-3, 18/05522-9, 16/12234-4)
PEREIRA, ARTHUR O.; BARROS, NICOLE M. A.; GUERRERO, BRUNA R.; EMENCHETA, STEPHEN C.; BALDO, DENICEZAR A.; OLIVEIRA JR., JOSE M.; VILA, MARTA M. D. C.; BALCAO, VICTOR M.. An Edible Biopolymeric Microcapsular Wrapping Integrating Lytic Bacteriophage Particles for Salmonella enterica: Potential for Integration into Poultry Feed. ANTIBIOTICS-BASEL, v. 12, n. 6, p. 33-pg., . (18/05522-9, 22/10775-9, 16/12234-4, 16/08884-3)
ROSA MITELMAO, FABIANA CRISTINA; BERGAMASCHI, CRISTIANE DE CASSIA; GERENUTTI, MARLI; HACHEL, KARIN; SILVA, MARCUS TOLENTINO; BALCAO, VICTOR M.; DUARTE CARVALHO VILA, MARTA MARIA. The effect of probiotics on functional constipation in adults Double-blind, randomized, placebo-controlled study. MEDICINE, v. 100, n. 10, . (16/12234-4, 16/08884-3, 18/05522-9)
HARADA, LILIAM K.; SILVA, ERICA C.; CAMPOS, WELIDA F.; DEL FIOL, FERNANDO S.; VILA, MARTA; DABROWSKA, KRYSTYNA; KRYLOV, VICTOR N.; BALCAO, VICTOR M.. Biotechnological applications of bacteriophages: State of the art. MICROBIOLOGICAL RESEARCH, v. 212, p. 38-58, . (16/08884-3, 16/16641-3, 16/12234-4)
HARADA, LILIAM K.; PEREIRA, JORGE F. B.; CAMPOS, WELIDA F.; SILVA, ERICA C.; MOUTINHO, CARLA G.; VILA, MARTA M. D. C.; OLIVEIRA, JR., JOSE M.; TEIXEIRA, JOSE A.; BALCAO, VICTOR M.; TUBINO, MATTHIEU. Insights into Protein-Ionic Liquid Interactions Aiming at Macromolecule Delivery Systems. Journal of the Brazilian Chemical Society, v. 29, n. 10, p. 1983-1998, . (16/16641-3, 16/12234-4, 16/08884-3)

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