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Interactions of Gold and Silver Nanoparticles with Bacterial Biofilms: Molecular Interactions behind Inhibition and Resistance.
Joshi, AS, Singh, P, Mijakovic, I
International journal of molecular sciences. 2020;(20)
Abstract
Many bacteria have the capability to form a three-dimensional, strongly adherent network called 'biofilm'. Biofilms provide adherence, resourcing nutrients and offer protection to bacterial cells. They are involved in pathogenesis, disease progression and resistance to almost all classical antibiotics. The need for new antimicrobial therapies has led to exploring applications of gold and silver nanoparticles against bacterial biofilms. These nanoparticles and their respective ions exert antimicrobial action by damaging the biofilm structure, biofilm components and hampering bacterial metabolism via various mechanisms. While exerting the antimicrobial activity, these nanoparticles approach the biofilm, penetrate it, migrate internally and interact with key components of biofilm such as polysaccharides, proteins, nucleic acids and lipids via electrostatic, hydrophobic, hydrogen-bonding, Van der Waals and ionic interactions. Few bacterial biofilms also show resistance to these nanoparticles through similar interactions. The nature of these interactions and overall antimicrobial effect depend on the physicochemical properties of biofilm and nanoparticles. Hence, study of these interactions and participating molecular players is of prime importance, with which one can modulate properties of nanoparticles to get maximal antibacterial effects against a wide spectrum of bacterial pathogens. This article provides a comprehensive review of research specifically directed to understand the molecular interactions of gold and silver nanoparticles with various bacterial biofilms.
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Synergy between induction heating, antibiotics, and N-acetylcysteine eradicates Staphylococcus aureus from biofilm.
Pijls, BG, Sanders, IMJG, Kuijper, EJ, Nelissen, RGHH
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2020;(1):130-136
Abstract
Background: Non-contact induction heating (NCIH) is a noninvasive treatment modality that can be used to cause thermal damage to bacterial biofilms on a metal implant surface in the context of a prosthetic joint infection. The purpose of this study was (1) to determine the effectiveness of NCIH on killing Staphylococcus aureus from biofilm and (2) to determine the possible synergistic effect of NCIH and cocktails of antibiotics and N-acetylcysteine (NAC).Methods:Staphylococcus aureus biofilms were grown on titanium alloy (Ti6Al4V) coupons. These coupons were heated to 50 °C, 60 °C, 70 °C, 80 °C, and 90 °C for 3.5 min and subsequently exposed to cocktails of vancomycin, rifampicin and NAC at clinically relevant concentrations over 24 h.Results: In the control group without induction heating, 2.2*107 colony forming units (CFU)/cm2 were observed. At 50 °C, 60 °C, 70 °C, 80 °C, and 90 °C, a reduction of 0.3-log, 3.9-log, 4.2-log, 4.3-log, and 6.6-log CFU/cm2 were observed, respectively. There was synergy between antibiotics and induction heating that resulted in less than 100 CFU/cm2 remaining after 3.5 min at 60 °C, and exposure to vancomycin and rifampicin. Total eradication was observed at 80 °C. Total eradication was also observed at 60 °C and a cocktail of antibiotics with NAC.Conclusion: Induction heating of titanium alloy coupons is effective for the reduction of bacterial load in vitro in S. aureus biofilms. Induction heating and cocktails of antibiotics and NAC have a synergistic effect that results in the total eradication of the biofilm at 60 °C and higher for clinically relevant concentrations of vancomycin, rifampicin and NAC.
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Novel bis(pyrazole-benzofuran) hybrids possessing piperazine linker: Synthesis of potent bacterial biofilm and MurB inhibitors.
Mekky, AEM, Sanad, SMH
Bioorganic chemistry. 2020;:104094
Abstract
Novel 1,4-bis[(2-(3-(dimethylamino)-1-oxoprop-2-en-1-yl)benzofuran-5-yl)methyl]piperazine was prepared and used as a key synthon for the this study. Therefore, 1,3-dipolar cycloaddition of this synthon with the appropriate hydrazonyl chlorides afforded a new series of bis(1,3,4-trisubstituted pyrazoles), linked via piperazine moiety. Furthermore, it reacted with hydrazine hydrate and phenyl hydrazine individually to afford the corresponding 1,4-bis[(2-(1H-pyrazolyl)benzofuran-5-yl)methyl]piperazines. Different bacterial strains and cell lines were selected to study the in-vitro antibacterial and cytotoxic activities for the new derivatives. 1,4-Bis[((2-(3-acetyl-1-(4-nitrophenyl)-1H-pyrazole-4-yl)carbonyl)benzofuran-5-yl)methyl]piperazine 5e showed the best antibacterial efficacies with MIC/MBC values of 1.2/1.2, 1.2/2.4 and 1.2/2.4 μM against each of E. coli, S. aureus and S. mutans strains, respectively. In addition, the inhibitory activity of some new bis(pyrazoles) as MRSA and VRE inhibitors were studied. Compound 5e gave the best inhibitory activity with MIC/MBC values of 18.1/36.2, 9.0/18.1 and 18.1/18.1 µM, respectively, against MRSA (ATCC:33591 and ATCC43300) and VRE (ATCC:51575) bacterial strains, respectively. Compound 5e showed more effective biofilm inhibition activities than the reference Ciprofloxacin. It showed IC50 values of 3.0 ± 0.05, 3.2 ± 0.08 and 3.3 ± 0.07 μM against S. aureus, S. mutans and E. coli strains, respectively. Furthermore, experimental study showed excellent inhibitory activities of 1,4-bis[((2-(3-substituted-1-aryl-1H-pyrazole-4-yl)carbonyl)benzofuran-5-yl)methyl]piperazine derivatives, attached to p-NO2 or p-Cl groups, against MurB enzyme. Compound 5e gave the best MurB inhibitory activity with IC50 value of 3.1 μM. The in-silico study was performed to predict the capability of new derivatives as potential inhibitors of MurB enzyme.
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Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde.
da Nóbrega Alves, D, Monteiro, AFM, Andrade, PN, Lazarini, JG, Abílio, GMF, Guerra, FQS, Scotti, MT, Scotti, L, Rosalen, PL, Castro, RD
Molecules (Basel, Switzerland). 2020;(24)
Abstract
OBJECTIVE This study evaluated the antifungal activity of cinnamaldehyde on Candida spp. In vitro and in situ assays were carried out to test cinnamaldehyde for its anti-Candida effects, antibiofilm activity, effects on fungal micromorphology, antioxidant activity, and toxicity on keratinocytes and human erythrocytes. Statistical analysis was performed considering α = 5%. RESULTS The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of cinnamaldehyde ranged from 18.91 μM to 37.83 μM. MIC values did not change in the presence of 0.8 M sorbitol, whereas an 8-fold increase was observed in the presence of ergosterol, suggesting that cinnamaldehyde may act on the cell membrane, which was subsequently confirmed by docking analysis. The action of cinnamaldehyde likely includes binding to enzymes involved in the formation of the cytoplasmic membrane in yeast cells. Cinnamaldehyde-treated microcultures showed impaired cellular development, with an expression of rare pseudo-hyphae and absence of chlamydoconidia. Cinnamaldehyde reduced biofilm adherence by 64.52% to 33.75% (p < 0.0001) at low concentrations (378.3-151.3 µM). Cinnamaldehyde did not show antioxidant properties. CONCLUSIONS Cinnamaldehyde showed fungicidal activity through a mechanism of action likely related to ergosterol complexation; it was non-cytotoxic to keratinocytes and human erythrocytes and showed no antioxidant activity.
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3D biofilms: in search of the polysaccharides holding together lichen symbioses.
Spribille, T, Tagirdzhanova, G, Goyette, S, Tuovinen, V, Case, R, Zandberg, WF
FEMS microbiology letters. 2020;(5)
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Abstract
Stable, long-term interactions between fungi and algae or cyanobacteria, collectively known as lichens, have repeatedly evolved complex architectures with little resemblance to their component parts. Lacking any central scaffold, the shapes they assume are casts of secreted polymers that cement cells into place, determine the angle of phototropic exposure and regulate water relations. A growing body of evidence suggests that many lichen extracellular polymer matrices harbor unicellular, non-photosynthesizing organisms (UNPOs) not traditionally recognized as lichen symbionts. Understanding organismal input and uptake in this layer is key to interpreting the role UNPOs play in lichen biology. Here, we review both polysaccharide composition determined from whole, pulverized lichens and UNPOs reported from lichens to date. Most reported polysaccharides are thought to be structural cell wall components. The composition of the extracellular matrix is not definitively known. Several lines of evidence suggest some acidic polysaccharides have evaded detection in routine analysis of neutral sugars and may be involved in the extracellular matrix. UNPOs reported from lichens include diverse bacteria and yeasts for which secreted polysaccharides play important biological roles. We conclude by proposing testable hypotheses on the role that symbiont give-and-take in this layer could play in determining or modifying lichen symbiotic outcomes.
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Metabolic Heterogeneity and Cross-Feeding in Bacterial Multicellular Systems.
Evans, CR, Kempes, CP, Price-Whelan, A, Dietrich, LEP
Trends in microbiology. 2020;(9):732-743
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Abstract
Cells in assemblages differentiate and perform distinct roles. Though many pathways of differentiation are understood at the molecular level in multicellular eukaryotes, the elucidation of similar processes in bacterial assemblages is recent and ongoing. Here, we discuss examples of bacterial differentiation, focusing on cases in which distinct metabolisms coexist and those that exhibit cross-feeding, with one subpopulation producing substrates that are metabolized by a second subpopulation. We describe several studies of single-species systems, then segue to studies of multispecies metabolic heterogeneity and cross-feeding in the clinical setting. Many of the studies described exemplify the application of new techniques and modeling approaches that provide insights into metabolic interactions relevant for bacterial growth outside the laboratory.
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Addressing the challenges in antisepsis: focus on povidone iodine.
Barreto, R, Barrois, B, Lambert, J, Malhotra-Kumar, S, Santos-Fernandes, V, Monstrey, S
International journal of antimicrobial agents. 2020;(3):106064
Abstract
OBJECTIVES Using antiseptics in wound care can promote healing by preventing and treating infection. However, using antiseptics can present many challenges, including issues with tolerability, inactivation by organic matter and the emergence of antimicrobial resistance/cross-resistance. This review discussed the key challenges in antisepsis, focusing on povidone-iodine (PVP-I) antiseptic. METHODS Literature searches were conducted in PubMed, in January 2019, with a filter for the previous 5 years. Searches were based on the antimicrobial efficacy, antiseptic resistance, wound healing properties, and skin tolerability for the commonly used antiseptics PVP-I, chlorhexidine gluconate (CHG), polyhexanide (PHMB), and octenidine (OCT). Additional papers were identified based on author expertise. RESULTS When compared with CHG, PHMB and OCT, PVP-I had a broader spectrum of antimicrobial activity against Gram-negative bacteria, actinobacteria, bacterial spores, fungi and viruses, and a similar and broad spectrum of activity against Gram-positive bacteria. PVP-I was also highly effective at eradicating bacterial biofilms, which is a vitally important consideration for wound care and infection control. Despite a long history of extensive use, no resistance or cross-resistance to PVP-I has been recorded, which is in contrast with other antiseptics. Despite previous misconceptions, it has been shown that PVP-I has low allergenic properties, low cytotoxicity and can promote wound healing through increased expression of transforming growth factor beta. CONCLUSION With increased understanding of the importance of tackling antimicrobial resistance and bacterial biofilms in acute and chronic wound care, alongside improved understanding of the challenges of antiseptic use, PVP-I remains a promising agent for the management of antisepsis.
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Alterocin, an Antibiofilm Protein Secreted by Pseudoalteromonas sp. Strain 3J6.
Jouault, A, Gobet, A, Simon, M, Portier, E, Perennou, M, Corre, E, Gaillard, F, Vallenet, D, Michel, G, Fleury, Y, et al
Applied and environmental microbiology. 2020;(20)
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Abstract
We sought to identify and study the antibiofilm protein secreted by the marine bacterium Pseudoalteromonas sp. strain 3J6. The latter is active against marine and terrestrial bacteria, including Pseudomonas aeruginosa clinical strains forming different biofilm types. Several amino acid sequences were obtained from the partially purified antibiofilm protein, named alterocin. The Pseudoalteromonas sp. 3J6 genome was sequenced, and a candidate alt gene was identified by comparing the genome-encoded proteins to the sequences from purified alterocin. Expressing the alt gene in another nonactive Pseudoalteromonas sp. strain, 3J3, demonstrated that it is responsible for the antibiofilm activity. Alterocin is a 139-residue protein that includes a predicted 20-residue signal sequence, which would be cleaved off upon export by the general secretion system. No sequence homology was found between alterocin and proteins of known functions. The alt gene is not part of an operon and adjacent genes do not seem related to alterocin production, immunity, or regulation, suggesting that these functions are not fulfilled by devoted proteins. During growth in liquid medium, the alt mRNA level peaked during the stationary phase. A single promoter was experimentally identified, and several inverted repeats could be binding sites for regulators. alt genes were found in about 30% of the Pseudoalteromonas genomes and in only a few instances of other marine bacteria of the Hahella and Paraglaciecola genera. Comparative genomics yielded the hypothesis that alt gene losses occurred within the Pseudoalteromonas genus. Overall, alterocin is a novel kind of antibiofilm protein of ecological and biotechnological interest.IMPORTANCE Biofilms are microbial communities that develop on solid surfaces or interfaces and are detrimental in a number of fields, including for example food industry, aquaculture, and medicine. In the latter, antibiotics are insufficient to clear biofilm infections, leading to chronic infections such as in the case of infection by Pseudomonas aeruginosa of the lungs of cystic fibrosis patients. Antibiofilm molecules are thus urgently needed to be used in conjunction with conventional antibiotics, as well as in other fields of application, especially if they are environmentally friendly molecules. Here, we describe alterocin, a novel antibiofilm protein secreted by a marine bacterium belonging to the Pseudoalteromonas genus, and its gene. Alterocin homologs were found in about 30% of Pseudoalteromonas strains, indicating that this new family of antibiofilm proteins likely plays an important albeit nonessential function in the biology of these bacteria. This study opens up the possibility of a variety of applications.
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Plant Derived Natural Products against Pseudomonas aeruginosa and Staphylococcus aureus: Antibiofilm Activity and Molecular Mechanisms.
Guzzo, F, Scognamiglio, M, Fiorentino, A, Buommino, E, D'Abrosca, B
Molecules (Basel, Switzerland). 2020;(21)
Abstract
Bacteria are social organisms able to build complex structures, such as biofilms, that are highly organized surface-associated communities of microorganisms, encased within a self- produced extracellular matrix. Biofilm is commonly associated with many health problems since its formation increases resistance to antibiotics and antimicrobial agents, as in the case of Pseudomonas aeruginosa and Staphylococcus aureus, two human pathogens causing major concern. P. aeruginosa is responsible for severe nosocomial infections, the most frequent of which is ventilator-associated pneumonia, while S. aureus causes several problems, like skin infections, septic arthritis, and endocarditis, to name just a few. Literature data suggest that natural products from plants, bacteria, fungi, and marine organisms have proven to be effective as anti-biofilm agents, inhibiting the formation of the polymer matrix, suppressing cell adhesion and attachment, and decreasing the virulence factors' production, thereby blocking the quorum sensing network. Here, we focus on plant derived chemicals, and provide an updated literature review on the anti-biofilm properties of terpenes, flavonoids, alkaloids, and phenolic compounds. Moreover, whenever information is available, we also report the mechanisms of action.
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Nonuniform growth and surface friction determine bacterial biofilm morphology on soft substrates.
Fei, C, Mao, S, Yan, J, Alert, R, Stone, HA, Bassler, BL, Wingreen, NS, Košmrlj, A
Proceedings of the National Academy of Sciences of the United States of America. 2020;(14):7622-7632
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During development, organisms acquire three-dimensional (3D) shapes with important physiological consequences. While basic mechanisms underlying morphogenesis are known in eukaryotes, it is often difficult to manipulate them in vivo. To circumvent this issue, here we present a study of developing Vibrio cholerae biofilms grown on agar substrates in which the spatiotemporal morphological patterns were altered by varying the agar concentration. Expanding biofilms are initially flat but later undergo a mechanical instability and become wrinkled. To gain mechanistic insights into this dynamic pattern-formation process, we developed a model that considers diffusion of nutrients and their uptake by bacteria, bacterial growth/biofilm matrix production, mechanical deformation of both the biofilm and the substrate, and the friction between them. Our model shows quantitative agreement with experimental measurements of biofilm expansion dynamics, and it accurately predicts two distinct spatiotemporal patterns observed in the experiments-the wrinkles initially appear either in the peripheral region and propagate inward (soft substrate/low friction) or in the central region and propagate outward (stiff substrate/high friction). Our results, which establish that nonuniform growth and friction are fundamental determinants of stress anisotropy and hence biofilm morphology, are broadly applicable to bacterial biofilms with similar morphologies and also provide insight into how other bacterial biofilms form distinct wrinkle patterns. We discuss the implications of forming undulated biofilm morphologies, which may enhance the availability of nutrients and signaling molecules and serve as a "bet hedging" strategy.