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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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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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Abstract
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.
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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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Treating infections with ionizing radiation: a historical perspective and emerging techniques.
van Dijk, B, Lemans, JVC, Hoogendoorn, RM, Dadachova, E, de Klerk, JMH, Vogely, HC, Weinans, H, Lam, MGEH, van der Wal, BCH
Antimicrobial resistance and infection control. 2020;(1):121
Abstract
BACKGROUND Widespread use and misuse of antibiotics have led to a dramatic increase in the emergence of antibiotic resistant bacteria, while the discovery and development of new antibiotics is declining. This has made certain implant-associated infections such as periprosthetic joint infections, where a biofilm is formed, very difficult to treat. Alternative treatment modalities are needed to treat these types of infections in the future. One candidate that has been used extensively in the past, is the use of ionizing radiation. This review aims to provide a historical overview and future perspective of radiation therapy in infectious diseases with a focus on orthopedic infections. METHODS A systematic search strategy was designed to select studies that used radiation as treatment for bacterial or fungal infections. A total of 216 potentially relevant full-text publications were independently reviewed, of which 182 focused on external radiation and 34 on internal radiation. Due to the large number of studies, several topics were chosen. The main advantages, disadvantages, limitations, and implications of radiation treatment for infections were discussed. RESULTS In the pre-antibiotic era, high mortality rates were seen in different infections such as pneumonia, gas gangrene and otitis media. In some cases, external radiation therapy decreased the mortality significantly but long-term follow-up of the patients was often not performed so long term radiation effects, as well as potential increased risk of malignancies could not be investigated. Internal radiation using alpha and beta emitting radionuclides show great promise in treating fungal and bacterial infections when combined with selective targeting through antibodies, thus minimizing possible collateral damage to healthy tissue. CONCLUSION The novel prospects of radiation treatment strategies against planktonic and biofilm-related microbial infections seem feasible and are worth investigating further. However, potential risks involving radiation treatment must be considered in each individual patient.
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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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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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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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Arginine as an environmental and metabolic cue for cyclic diguanylate signalling and biofilm formation in Pseudomonas putida.
Barrientos-Moreno, L, Molina-Henares, MA, Ramos-González, MI, Espinosa-Urgel, M
Scientific reports. 2020;(1):13623
Abstract
Cyclic diguanylate (c-di-GMP) is a broadly conserved intracellular second messenger that influences different bacterial processes, including virulence, stress tolerance or social behaviours and biofilm development. Although in most cases the environmental cue that initiates the signal transduction cascade leading to changes in cellular c-di-GMP levels remains unknown, certain L- and D-amino acids have been described to modulate c-di-GMP turnover in some bacteria. In this work, we have analysed the influence of L-amino acids on c-di-GMP levels in the plant-beneficial bacterium Pseudomonas putida KT2440, identifying L-arginine as the main one causing a significant increase in c-di-GMP. Both exogenous (environmental) and endogenous (biosynthetic) L-arginine influence biofilm formation by P. putida through changes in c-di-GMP content and altered expression of structural elements of the biofilm extracellular matrix. The contribution of periplasmic binding proteins forming part of amino acid transport systems to the response to environmental L-arginine was also studied. Contrary to what has been described in other bacteria, in P. putida these proteins seem not to be directly responsible for signal transduction. Rather, their contribution to global L-arginine pools appears to determine changes in c-di-GMP turnover. We propose that arginine plays a connecting role between cellular metabolism and c-di-GMP signalling in P. putida.
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Antimicrobial photodynamic therapy effectiveness against susceptible and methicillin-resistant Staphylococcus aureus biofilms.
Teixeira, CGS, Sanitá, PV, Ribeiro, APD, Dias, LM, Jorge, JH, Pavarina, AC
Photodiagnosis and photodynamic therapy. 2020;:101760
Abstract
BACKGROUND Staphylococcus aureus have a great ability to become rapidly resistant to conventional antimicrobial therapies. This study evaluated the efficacy of antimicrobial photodynamic therapy (aPDT) mediated by Curcumin (Cur) and light-emitting diode (LED) in the inactivation of biofilms of methicillin susceptible and resistant S. aureus (MSSA and MRSA, respectively). METHODS Biofilms were treated with Cur (20, 40 or 80 μM) and illuminated with LED source (455 ± 3 nm; 5.28 J/cm2) (aPDT groups), or treated either with Cur or LED only. Other samples were not exposed to Cur or LED (negative control). The biofilms viability after all experimental conditions were evaluated by counting the number of colonies (CFU/mL) and XTT assay. Additional samples were also evaluated by LIVE/DEAD® staining using confocal laser scanning microscopy (CLSM). Data were analyzed by ANOVAs followed by the Games-Howell post hoc test (α = 0.05). RESULTS For both strains, all aPDT groups significantly reduced both CFU/mL and metabolic activity of biofilms compared to the negative control (p < 0.001). The results were enhanced when 80 μM of Cur was used. CLSM images showed that both bacteria biofilms submitted to aPDT had a large number of red-stained colonies, especially at aPDT80. In general, MRSA biofilms tended to be less susceptible to aPDT than MSSA biofilms. CONCLUSIONS It can be concluded that aPDT mediated by Cur and LED was an efficient method to inactivate 48 -h biofilms of both S. aureus strains.
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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.