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1.
Approaches to Targeting Bacterial Biofilms in Cystic Fibrosis Airways.
Martin, I, Waters, V, Grasemann, H
International journal of molecular sciences. 2021;(4)
Abstract
The treatment of lung infection in the context of cystic fibrosis (CF) is limited by a biofilm mode of growth of pathogenic organisms. When compared to planktonically grown bacteria, bacterial biofilms can survive extremely high levels of antimicrobials. Within the lung, bacterial biofilms are aggregates of microorganisms suspended in a matrix of self-secreted proteins within the sputum. These structures offer both physical protection from antibiotics as well as a heterogeneous population of metabolically and phenotypically distinct bacteria. The bacteria themselves and the components of the extracellular matrix, in addition to the signaling pathways that direct their behaviour, are all potential targets for therapeutic intervention discussed in this review. This review touches on the successes and failures of current anti-biofilm strategies, before looking at emerging therapies and the mechanisms by which it is hoped they will overcome current limitations.
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2.
Comparative Biofilm Assays Using Enterococcus faecalis OG1RF Identify New Determinants of Biofilm Formation.
Willett, JLE, Dale, JL, Kwiatkowski, LM, Powers, JL, Korir, ML, Kohli, R, Barnes, AMT, Dunny, GM
mBio. 2021;(3):e0101121
Abstract
Enterococcus faecalis is a common commensal organism and a prolific nosocomial pathogen that causes biofilm-associated infections. Numerous E. faecalis OG1RF genes required for biofilm formation have been identified, but few studies have compared genetic determinants of biofilm formation and biofilm morphology across multiple conditions. Here, we cultured transposon (Tn) libraries in CDC biofilm reactors in two different media and used Tn sequencing (TnSeq) to identify core and accessory biofilm determinants, including many genes that are poorly characterized or annotated as hypothetical. Multiple secondary assays (96-well plates, submerged Aclar discs, and MultiRep biofilm reactors) were used to validate phenotypes of new biofilm determinants. We quantified biofilm cells and used fluorescence microscopy to visualize biofilms formed by six Tn mutants identified using TnSeq and found that disrupting these genes (OG1RF_10350, prsA, tig, OG1RF_10576, OG1RF_11288, and OG1RF_11456) leads to significant time- and medium-dependent changes in biofilm architecture. Structural predictions revealed potential roles in cell wall homeostasis for OG1RF_10350 and OG1RF_11288 and signaling for OG1RF_11456. Additionally, we identified growth medium-specific hallmarks of OG1RF biofilm morphology. This study demonstrates how E. faecalis biofilm architecture is modulated by growth medium and experimental conditions and identifies multiple new genetic determinants of biofilm formation. IMPORTANCE E. faecalis is an opportunistic pathogen and a leading cause of hospital-acquired infections, in part due to its ability to form biofilms. A complete understanding of the genes required for E. faecalis biofilm formation as well as specific features of biofilm morphology related to nutrient availability and growth conditions is crucial for understanding how E. faecalis biofilm-associated infections develop and resist treatment in patients. We employed a comprehensive approach to analysis of biofilm determinants by combining TnSeq primary screens with secondary phenotypic validation using diverse biofilm assays. This enabled identification of numerous core (important under many conditions) and accessory (important under specific conditions) biofilm determinants in E. faecalis OG1RF. We found multiple genes whose disruption results in drastic changes to OG1RF biofilm morphology. These results expand our understanding of the genetic requirements for biofilm formation in E. faecalis that affect the time course of biofilm development as well as the response to specific nutritional conditions.
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3.
The effect of the combined use of silver diamine fluoride and potassium iodide in disrupting the plaque biofilm microbiome and alleviating tooth discoloration: A systematic review.
Haiat, A, Ngo, HC, Samaranayake, LP, Fakhruddin, KS
PloS one. 2021;(6):e0252734
Abstract
Silver diamine fluoride (SDF) is used in minimally invasive dentistry for arresting dental caries. However, discoloration of teeth is a significant side effect that has limited the use of SDF. Hence, the application of potassium iodide (KI) following SDF has been proposed to ameliorate the staining. Although antimicrobial activity is one of the major mechanisms of the caries-arresting effect of SDF, the antimicrobial potency of SDF/KI combination is unclear. Thus, the primary objective of this systematic review was to appraise the studies on the antimicrobial efficacy of SDF/KI combination on cariogenic microbes. The secondary objective was to summarize the evidence on the potential of KI in reducing the discoloration associated with the application of SDF. Electronic databases of Medline via PubMed, Cochrane Library, Web of Science, and EBSCO host were searched for English language manuscripts from January 2005 to 15th November 2020. The reference lists of these manuscripts were manually searched for additional studies. Twelve studies were included in the final analysis, seven of which have investigated the antimicrobial efficacy of SDF/KI, and the rest have examined the anti-staining potential of KI. The exploratory findings from the reviewed articles revealed the promising antimicrobial potential of SDF/KI on cariogenic microbes associated with dentine caries. There is, however, contradictory evidence on the effect of SDF/KI on tooth color. The reviewed in-vitro studies indicated significant effectiveness of KI in preventing staining. A clinical trial on primary dentition showed 25% reduction in the incidence of staining by SDF after applying KI, while a clinical study on root caries in adults showed no significant effect. Within the methodological limitations of this review, we conclude that for arresting dental caries, SDF could be combined with KI, as there may be a lower likelihood of staining. Further, well-designed clinical trials on the antimicrobial and anti-staining effect of SDF/KI are needed to obtain more robust evidence.
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4.
Interactive effects of discharge reduction and fine sediments on stream biofilm metabolism.
Pérez-Calpe, AV, Larrañaga, A, von Schiller, D, Elosegi, A
PloS one. 2021;(2):e0246719
Abstract
Discharge reduction, as caused by water diversion for hydropower, and fine sediments deposition, are prevalent stressors that may affect multiple ecosystem functions in streams. Periphytic biofilms play a key role in stream ecosystem functioning and are potentially affected by these stressors and their interaction. We experimentally assessed the interactive effects of discharge and fine sediments on biofilm metabolism in artificial indoor channels using a factorial split-plot design with two explanatory variables: water discharge (20, 39, 62, 141 and 174 cm3 s-1) and fine sediments (no sediment or 1100 mg L-1 of sediments). We incubated artificial tiles for 25 days in an unpolluted stream to allow biofilm colonization, and then placed them into the indoor channels for acclimation for 18 days. Subsequently, we manipulated water discharge and fine sediments and, after 17 days, we measured biofilm chlorophyll-a concentration and metabolism. Water velocity (range, 0.5 to 3.0 cm s-1) and sediment deposition (range, 6.1 to 16.6 mg cm-2) increased with discharge, the latter showing that the effect of increased inputs prevailed over sloughing. In the no-sediment treatments, discharge did not affect biofilm metabolism, but reduced chlorophyll-a. Sediments, probably as a consequence of nutrients released, promoted metabolism of biofilm and chlorophyll-a, which became independent of water discharge. Our results indicate that pulses of fine sediments can promote biofilm algal biomass and metabolism, but show interactive effects with discharge. Although discharge reduction can affect the abundance of basal resources for food webs, its complex interactions with fine sediments make it difficult to forecast the extent and direction of the changes.
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5.
Combinatorial therapy of chitosan hydrogel-based zinc oxide nanocomposite attenuates the virulence of Streptococcus mutans.
Afrasiabi, S, Bahador, A, Partoazar, A
BMC microbiology. 2021;(1):62
Abstract
BACKGROUND Biofilm formation is an important causative factor in the expansion of the carious lesions in the enamel. Hence, new approaches to efficient antibacterial agents are highly demanded. This study was conducted to evaluate the antimicrobial-biofilm activity of chitosan hydrogel (CS gel), zinc oxide/ zeolite nanocomposite (ZnONC) either separately or combined together [ZnONC / CS gel (ZnONC-CS)] against Streptococcus mutans biofilm. RESULTS MTT assay demonstrated that the ZnONC-CS exhibits a non-cytotoxic effect (> 90% cell viability) toward human gingival fibroblast cells at different dosages (78.1-625 μg/mL) within 72 h. In comparison with CS gel and ZnONC, ZnONC-CS was superior at biofilm formation and metabolic activity reduction by 33 and 45%, respectively; (P < 0.05). The field emission scanning electron microscopy micrographs of the biofilms grown on the enamel slabs were largely in concordance with the quantitative biofilm assay results. Consistent with the reducing effect of ZnONC-CS on biofilm formation, the expression levels of gtfB, gtfC, and ftf significantly decreased. CONCLUSIONS Taken together, excellent compatibility coupled with an enhanced antimicrobial effect against S. mutans biofilm has equipped ZnONC-CS as a promising candidate for dental biofilm control.
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6.
Iron metabolism in Pseudomonas aeruginosa biofilm and the involved iron-targeted anti-biofilm strategies.
Zhang, Y, Pan, X, Wang, L, Chen, L
Journal of drug targeting. 2021;(3):249-258
Abstract
Pseudomonas aeruginosa is a gram-negative bacterium that exists in various ecosystems, causing severe infections in patients with AIDS or cystic fibrosis. P. aeruginosa can form biofilm on a variety of surfaces, whereby the bacteria produce defensive substances and enhance antibiotic-resistance, making themselves more adaptable to hostile environments. P. aeruginosa resistance represents one of the main causes of infection-related morbidity and mortality at a global level. Iron is required for the growth of P. aeruginosa biofilm. This review summarises how the iron metabolism contributes to develop biofilm, and more importantly, it may provide some references for the clinic to achieve novel anti-biofilm therapeutics by targeting iron activities.
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7.
Extracellular Metabolism Sets the Table for Microbial Cross-Feeding.
Fritts, RK, McCully, AL, McKinlay, JB
Microbiology and molecular biology reviews : MMBR. 2021;(1)
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Free full text
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Abstract
The transfer of nutrients between cells, or cross-feeding, is a ubiquitous feature of microbial communities with emergent properties that influence our health and orchestrate global biogeochemical cycles. Cross-feeding inevitably involves the externalization of molecules. Some of these molecules directly serve as cross-fed nutrients, while others can facilitate cross-feeding. Altogether, externalized molecules that promote cross-feeding are diverse in structure, ranging from small molecules to macromolecules. The functions of these molecules are equally diverse, encompassing waste products, enzymes, toxins, signaling molecules, biofilm components, and nutrients of high value to most microbes, including the producer cell. As diverse as the externalized and transferred molecules are the cross-feeding relationships that can be derived from them. Many cross-feeding relationships can be summarized as cooperative but are also subject to exploitation. Even those relationships that appear to be cooperative exhibit some level of competition between partners. In this review, we summarize the major types of actively secreted, passively excreted, and directly transferred molecules that either form the basis of cross-feeding relationships or facilitate them. Drawing on examples from both natural and synthetic communities, we explore how the interplay between microbial physiology, environmental parameters, and the diverse functional attributes of extracellular molecules can influence cross-feeding dynamics. Though microbial cross-feeding interactions represent a burgeoning field of interest, we may have only begun to scratch the surface.
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The role of biofilm in the development and dissemination of ubiquitous pathogens in drinking water distribution systems: an overview of surveillance, outbreaks, and prevention.
Hemdan, BA, El-Taweel, GE, Goswami, P, Pant, D, Sevda, S
World journal of microbiology & biotechnology. 2021;(2):36
Abstract
A variety of pathogenic microorganisms can survive in the drinking water distribution systems (DWDS) by forming stable biofilms and, thus, continually disseminating their population through the system's dynamic water bodies. The ingestion of the pathogen-contaminated water could trigger a broad spectrum of illnesses and well-being-related obstacles. These waterborne diseases are a significant concern for babies, pregnant women, and significantly low-immune individuals. This review highlights the recent advances in understanding the microbiological aspects of drinking water quality, biofilm formation and its dynamics, health issues caused by the emerging microbes in biofilm, and approaches for biofilm investigation its prevention and suppression in DWDS.
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9.
Helicobacter pylori Biofilm and New Strategies to Combat it.
Moghadam, MT, Chegini, Z, Khoshbayan, A, Farahani, I, Shariati, A
Current molecular medicine. 2021;(7):549-561
Abstract
Helicobacter pylori, the most frequent pathogen worldwide that colonizes around 50% of the world's population, causes important diseases such as gastric adenocarcinoma, chronic gastritis, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In recent years, various studies have reported that H. pylori biofilm may be one of the critical barriers to the eradication of this bacterial infection. Biofilms inhibit the penetration of antibiotics, increase the expression of efflux pumps and mutations, multiple therapeutic failures, and chronic infections. Nanoparticles and natural products can demolish H. pylori biofilm by destroying the outer layers and inhibiting the initial binding of bacteria. Also, the use of combination therapies destroying extracellular polymeric substances decreases coccoid forms of bacteria and degrading polysaccharides in the outer matrix that lead to an increase in the permeability and performance of antibiotics. Different probiotics, antimicrobial peptides, chemical substances, and polysaccharides by inhibiting adhesion and colonization of H. pylori can prevent biofilm formation by this bacterium. Of note, many of the above are applicable to acidic pH and can be used to treat gastritis. Therefore, H. pylori biofilm may be one of the major causes of failure to eradication of infections caused by this bacterium, and antibiotics are not capable of destroying the biofilm. Thus, it is necessary to use new strategies to prevent recurrent and chronic infections by inhibiting biofilm formation.
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10.
Biofilm regulation in Clostridioides difficile: Novel systems linked to hypervirulence.
Taggart, MG, Snelling, WJ, Naughton, PJ, La Ragione, RM, Dooley, JSG, Ternan, NG
PLoS pathogens. 2021;(9):e1009817
Abstract
Clostridiodes difficile (C. difficile) was ranked an "urgent threat" by the Centers for Disease Control and Prevention (CDC) in 2019. C. difficile infection (CDI) is the most common healthcare-associated infection (HAI) in the United States of America as well as the leading cause of antibiotic-associated gastrointestinal disease. C. difficile is a gram-positive, rod-shaped, spore-forming, anaerobic bacterium that causes infection of the epithelial lining of the gut. CDI occurs most commonly after disruption of the human gut microflora following the prolonged use of broad-spectrum antibiotics. However, the recurrent nature of this disease has led to the hypothesis that biofilm formation may play a role in its pathogenesis. Biofilms are sessile communities of bacteria protected from extracellular stresses by a matrix of self-produced proteins, polysaccharides, and extracellular DNA. Biofilm regulation in C. difficile is still incompletely understood, and its role in disease recurrence has yet to be fully elucidated. However, many factors have been found to influence biofilm formation in C. difficile, including motility, adhesion, and hydrophobicity of the bacterial cells. Small changes in one of these systems can greatly influence biofilm formation. Therefore, the biofilm regulatory system would need to coordinate all these systems to create optimal biofilm-forming physiology under appropriate environmental conditions. The coordination of these systems is complex and multifactorial, and any analysis must take into consideration the influences of the stress response, quorum sensing (QS), and gene regulation by second messenger molecule cyclic diguanosine monophosphate (c-di-GMP). However, the differences in biofilm-forming ability between C. difficile strains such as 630 and the "hypervirulent" strain, R20291, make it difficult to assign a "one size fits all" mechanism to biofilm regulation in C. difficile. This review seeks to consolidate published data regarding the regulation of C. difficile biofilms in order to identify gaps in knowledge and propose directions for future study.