Novel approaches to control biofilm infections.
ABSTRACT Biofilms are matrix-enclosed microbial aggregations that adhere to biological or non-biological surfaces. They represent a significant and incompletely understood mode of growth for bacteria and fungi. Biofilm infections cause many deaths and high health costs worldwide. Biofilm infections on indwelling devices or implants are difficult to eradicate because of their much better protection against macrophages and antibiotics, compared to free living cells, leading to severe clinical complications often with lethal outcome. One promising approach to combat biofilm infections independent from the conventional control by antibiotics is the generation of functional surfaces preventing the attachment of bacteria. Another aim is the communication machinery used by bacteria to establish a biofilm, the so called quorum-sensing. Here, small diffusible compounds are produced and sensed by the producing cells to measure their concentration and hence cell density. Natural compounds and synthetic analogues have been used successfully to prevent biofilm formation by quorum-quenching. These compounds are still in the preclinical phase, often struggling with toxicity. A principal problem of quorum-quenchers is their high species specificity, resulting in the control of only some pathogenic strains leaving other pathogens untouched. A field still in its infancy is the control of virulence factors expression not preventing the biofilm but suppressing its virulence. This review will give an overview over the pros and cons of the individual targets and an outlook of future developments.
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ABSTRACT: Psidium guajava L., a traditionally used medicinal plant was explored for anti-quorum sensing (QS) activity. Anti-QS activity of flavonoid fraction (FL) of P. guajava leaves was determined using biosensor bioassay with Chromobacterium violaceum CV026. Detailed investigation on the effect of FL-fraction on QS-regulated violacein production in C. violaceum ATCC12472 and pyocyanin production, proteolytic, elastolytic activities, swarming motility and biofilm formation in Pseudomonas aeruginosa PAO1 were carried out using standard methods. Possible mechanism of QS-inhibition was studied by assessing the violacein production in response to AHL synthesis in presence of FL-fraction in C. violaceum ATCC31532 and by evaluating the induction of violacein in the mutant C. violaceum CV026 by the AHL extracted from the culture supernatants of C. violaceum 31532. Active compounds in the FL-fraction were identified using LC-MS analysis. Inhibition of violacein production by FL-fraction in C. violaceum CV026 biosensor bioassay indicated the possible anti-QS activity. FL-fraction showed concentration-dependent decrease in the violacein production in C. violaceum 12472 and inhibited pyocyanin production, proteolytic, elastolytic activities, swarming motility and biofilm formation in P. aeruginosa PAO1. Interestingly, FL-fraction did not inhibit AHL synthesis as the AHL extracted from the cultures of C. violaceum 31532 grown in presence of FL-fraction could induce violacein in the mutant C. violaceum CV026. LC-MS analysis revealed the presence of quercetin and quercetin-3-O-arabinoside in the FL-fraction. Both quercetin and quercetin-3-O-arabinoside inhibited violacein production in C. violaceum 12472 at 50 µg/ml and 100 µg/ml respectively. Results of this study provide scope for further research to exploit these active molecules as anti-QS agents.Microbiology and Immunology 04/2014; 58(5). DOI:10.1111/1348-0421.12150 · 1.31 Impact Factor
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ABSTRACT: Staphylococcus epidermidis is recognized as cause of biofilm-associated infections and interest in the development of new approaches for S. epidermidis biofilm treatment has increased. In a previous paper we reported that the supernatant of Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 presents an anti-biofilm activity against S. epidermidis and preliminary physico-chemical characterization of the supernatant suggested that this activity is due to a polysaccharide. In this work we further investigated the chemical nature of the anti-biofilm P. haloplanktis TAC125 molecule. The production of the molecule was evaluated in different conditions, and reported data demonstrated that it is produced in all P. haloplanktis TAC125 biofilm growth stages, also in minimal medium and at different temperatures. By using a surface coating assay, the surfactant nature of the anti-biofilm compound was excluded. Moreover, a purification procedure was set up and the analysis of an enriched fraction demonstrated that the anti-biofilm activity is not due to a polysaccharide molecule but that it is due to small hydrophobic molecules that likely work as signal. The enriched fraction was also used to evaluate the effect on S. epidermidis biofilm formation in dynamic condition by BioFlux system. © The Author(s) 2015.International journal of immunopathology and pharmacology 03/2015; 28(1):104-13. DOI:10.1177/0394632015572751 · 2.51 Impact Factor
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ABSTRACT: Biofilms are microbial sessile communities characterized by cells that are attached to a substratum or interface or to each other, are embedded in a self-produced matrix of extracellular polymeric substances and exhibit an altered phenotype compared to planktonic cells. Biofilms are estimated to be associated with 80% of microbial infections and it is currently common knowledge that growth of micro-organisms in biofilms can enhance their resistance to antimicrobial agents. As a consequence antimicrobial therapy often fails to eradicate biofilms from the site of infection. For this reason, innovative anti-biofilm agents with novel targets and modes of action are needed. One alternative approach is targeting the bacterial communication system (quorum sensing, QS). QS is a process by which bacteria produce and detect signal molecules and thereby coordinate their behavior in a cell-density dependent manner. Three main QS systems can be distinguished: the acylhomoserine lactone (AHL) QS system in Gram-negative bacteria, the autoinducing peptide (AIP) QS system in Gram-positive bacteria and the autoinducer-2 (AI-2) QS system in both Gram-negative and -positive bacteria. Although much remains to be learned about the involvement of QS in biofilm formation, maintenance, and dispersal, QS inhibitors (QSI) have been proposed as promising antibiofilm agents. In this article we will give an overview of QS inhibitors which have been shown to play a role in biofilm formation and/or maturation.Current Pharmaceutical Design 09/2014; DOI:10.2174/1381612820666140905114627 · 3.29 Impact Factor