In the new antibiotic era, the exponential increase in multiresistant bacterial strains has become the main global health problem. Many researchers have focused their efforts on exploring novel or combined strategies for combating bacterial resistance. Good knowledge of the molecular mechanisms of resistance and bacterial virulence factors as key targets provides us with a good basis for resolving the problem. One particularly attractive and promising strategy is to attack the main regulatory “network” of bacterial virulence determinants known as quorum sensing (QS). The inhibition of QS signals will be a novel means of screening more effective quorum-sensing inhibitors (QSIs) and will play a key role in the use of next-generation antimicrobials in the battle against resistance. This motivated the present review to provide a comprehensive clarification of the regulatory mechanisms of quorum-sensing signaling pathways in Chromobacterium violaceum and the discovery of potential plant quorum-sensing inhibitors.
Biofilm formation is considered one of the primary virulence mechanisms in Gram-positive and Gram-negative pathogenic species, particularly those responsible for chronic infections and promoting bacterial survival within the host. In recent years, there has been a growing interest in discovering new compounds capable of inhibiting biofilm formation. This is considered a promising antivirulence strategy that could potentially overcome antibiotic resistance issues. Effective antibiofilm agents should possess distinctive properties. They should be structurally unique, enable easy entry into cells, influence quorum sensing signaling, and synergize with other antibacterial agents. Many of these properties are found in both natural systems that are isolated from plants and in synthetic systems like nanoparticles and nanocomposites. In this review, we discuss the clinical nature of biofilm-associated infections and some of the mechanisms associated with their antibiotic tolerance. We focus on the advantages and efficacy of various natural and synthetic compounds as a new therapeutic approach to control bacterial biofilms and address multidrug resistance in bacteria.
The existence of biofilms as heterogeneous structures, comprising bacterial cells embedded in a self-synthesized polymeric matrix and adhered to biotic and abiotic surfaces, exhibiting high antibiotic tolerance, is a fact that, in recent years, has exerted selective pressure on healthcare systems with the emergence of numerous infections. This review provides a historical overview of the emergence of biofilms, the latest insights into their functionality and distribution, as well as data on innovative strategies to combat them. Special attention is given to significant diseases caused by biofilms, alongside current data on the molecular mechanisms underpinning their tolerance and resistance.
In the new antibiotic era, the exponential increase of multiresistant bacterial strains become the main global health problem. Many researchers focused their efforts to explore novel or combined strategies for combating bacterial resistance. The good knowledge of molecular mechanisms of resistance and bacterial virulence factors as key targets gives us a good scenario to resolve the problem. One particularly attractive and promising way is to attack the main regulatory “network” of bacterial virulence determinants known as Quorum sensing (QS). The inhibition of QS signals will be a novel way for screening more effective Quorum sensing inhibitors (QSIs) and will put a key role in next-generation antimicrobials in the resistance battle. This determined the aim of the present review: comprehensive clarification of the regulatory mechanisms of quorum-sensing signaling pathways in Chromobacterium violaceum and discovery of potential plant quorum sensing inhibitors.
Quercetin (QUE) is a bioactive flavonoid that is naturally present in various fruits and possesses many pharmacological activities. Despite its health benefits, the bioavailability of quercetin is relatively low due to its crystalline form and hydrophobic structure. An approach to overcoming these drawbacks is its incorporation into amorphous polymer matrices. PLA and PLA/PEG fibrous materials loaded with QUE were obtained by electrospinning. The XRD analysis revealed a visible decrease in the crystallinity of QUE after its incorporation into PLA and PLA/PEG fibers. The obtained fibrous materials and, especially, the PLA/PEG mat loaded with the flavonoid exhibited high antioxidant activity due to the better wettability and higher release rate of the bioactive compound. Moreover, the PLA/QUE and PLA/PEG/QUE mats possessed antibacterial properties against Staphylococcus aureus and Pseudomonas aeruginosa. Furthermore, the antitumor activity of the prepared mats was tested against SH-4 cancer cells and HaCaT keratinocytes. The obtained results reveal that the QUE-loaded fibrous mats exhibited high anticancer activity against cancer cells but lower toxicity to normal keratinocytes. The combined antioxidant, antibacterial and in vitro antitumor activities render these novel PLA-based materials loaded with QUE promising candidates for wound dressing applications and for application in local tumor treatment.
Biofilms are a well-known multifactorial virulence factor with a pivotal role in chronic bacterial infections. Their pathogenicity is determined by the combination of strain-specific mechanisms of virulence and the biofilm extracellular matrix (ECM) protecting the bacteria from the host immune defense and the action of antibacterials. The successful antibiofilm agents should combine antibacterial activity and good biocompatibility with the capacity to penetrate through the ECM. The objective of the study is the elaboration of biofilm-ECM-destructive drug delivery systems: mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA35-b-PCL70-b-PDMAEMA35) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO100-b-PPO65-b-PEO100) triblock copolymers, loaded with ciprofloxacin or azithromycin. The MPMs were applied on 24 h pre-formed biofilms of Escherichia coli and Pseudomonas aeruginosa (laboratory strains and clinical isolates). The results showed that the MPMs were able to destruct the biofilms, and the viability experiments supported drug delivery. The biofilm response to the MPMs loaded with the two antibiotics revealed two distinct patterns of action. These were registered on the level of both bacterial cell-structural alterations (demonstrated by scanning electron microscopy) and the interaction with host tissues (ex vivo biofilm infection model on skin samples with tests on nitric oxide and interleukin (IL)-17A production).