Quorum sensing inhibition by marine bacteria

Antibiotic resistance has been increasingly reported for a wide variety of bacteria of clinical significance. This widespread problem constitutes one of the greatest challenges of the twenty-first century. Faced with this issue, clinicians and researchers have been persuaded to design novel strategies in order to try to control pathogenic bacteria. Therefore, the discovery and elucidation of the mechanisms underlying bacterial pathogenesis and intercellular communication have opened new perspectives for the development of alternative approaches. Antipathogenic and/or antivirulence therapies based on the interruption of quorum sensing pathways are one of several such promising strategies aimed at disarming rather than at eradicating bacterial pathogens during the course of colonization and infection. This review describes mechanisms of bacterial communication involved in biofilm formation. An overview of the potential of marine bacteria and their bioactive components as QS inhibitors is further provided

Prevalence and Impact of Biofilms on Bloodstream and Urinary Tract Infections: A Systematic Review and Meta-Analysis

This study sought to assess the prevalence and impact of biofilms on two commonly biofilm-related infections, bloodstream and urinary tract infections (BSI and UTI). Separated systematic reviews and meta-analyses of observational studies were carried out in PubMed and Web of Sciences databases from January 2005 to May 2020, following PRISMA protocols. Studies were selected according to specific and defined inclusion/exclusion criteria. The obtained outcomes were grouped into biofilm production (BFP) prevalence, BFP in resistant vs. susceptible strains, persistent vs. non-persistent BSI, survivor vs. non-survivor patients with BSI, and catheter-associated UTI (CAUTI) vs. non-CAUTI. Single-arm and two-arm analyses were conducted for data analysis. In vitro BFP in BSI was highly related to resistant strains (odds ratio-OR: 2.68; 95% confidence intervals-CI: 1.60-4.47; p < 0.01), especially for methicillin-resistant Staphylococci. BFP was also highly linked to BSI persistence (OR: 2.65; 95% CI: 1.28-5.48; p < 0.01) and even to mortality (OR: 2.05; 95% CI: 1.53-2.74; p < 0.01). Candida spp. was the microorganism group where the highest associations were observed. Biofilms seem to impact Candida BSI independently from clinical differences, including treatment interventions. Regarding UTI, multi-drug resistant and extended-spectrum beta-lactamase-producing strains of Escherichia coli, were linked to a great BFP prevalence (OR: 2.92; 95% CI: 1.30-6.54; p < 0.01 and OR: 2.80; 95% CI: 1.33-5.86; p < 0.01). More in vitro BFP was shown in CAUTI compared to non-CAUTI, but with less statistical confidence (OR: 2.61; 95% CI: 0.67-10.17; p < 0.17). This study highlights that biofilms must be recognized as a BSI and UTI resistance factor as well as a BSI virulence factor

Biofilms in Surgical Site Infections: Recent Advances and Novel Prevention and Eradication Strategies

Surgical site infections (SSIs) are common postoperative occurrences due to contamination of the surgical wound or implanted medical devices with community or hospital-acquired microorganisms, as well as other endogenous opportunistic microbes. Despite numerous rules and guidelines applied to prevent these infections, SSI rates are considerably high, constituting a threat to the healthcare system in terms of morbidity, prolonged hospitalization, and death. Approximately 80% of human SSIs, including chronic wound infections, are related to biofilm-forming bacteria. Biofilm-associated SSIs are extremely difficult to treat with conventional antibiotics due to several tolerance mechanisms provided by the multidrug-resistant bacteria, usually arranged as polymicrobial communities. In this review, novel strategies to control, i.e., prevent and eradicate, biofilms in SSIs are presented and discussed, focusing mainly on two attractive approaches: the use of nanotechnology-based composites and natural plant-based products. An overview of new therapeutic agents and strategic approaches to control epidemic multidrug-resistant pathogenic microorganisms, particularly when biofilms are present, is provided alongside other combinatorial approaches as attempts to obtain synergistic effects with conventional antibiotics and restore their efficacy to treat biofilm-mediated SSIs. Some detection and real-time monitoring systems to improve biofilm control strategies and diagnosis of human infections are also discussed

Comparison of Techniques and Solvents on the Antimicrobial and Antioxidant Potential of Extracts from Acacia dealbata and Olea europaea

Ethnopharmacological use of plant natural extracts has been known since ancient times. The optimization of plant molecule extraction is fundamental in obtaining relevant extraction yields. The main purpose of this study was to understand the role of different extraction techniques (solid-liquid, ultrasound, Soxhlet, and microwave) and solvents (water, methanol, ethanol, acetone, dichloromethane, and hexane) on the antimicrobial and antioxidant activities of extracts from Olea europaea (olive) and Acacia dealbata (mimosa). Crude plant extracts were evaluated for their antimicrobial activity against Staphylococcus aureus and Escherichia coli by the disk diffusion method. The antioxidant capacity of the extracts was determined by ABTS (2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid)) and DPPH (2,2-diphenyl-1-picrylhydrazyl) methods. In terms of extraction yield, ultrasound extraction and the solvents methanol, acetone (O. europaea) or water (A. dealbata) were found to be the best options. However, ethanol and acetone proved to be the best solvents to extract compounds with antimicrobial activity and antioxidant capacity, respectively (regardless of the extraction method employed). Soxhlet and microwave were the best techniques to extract compounds with antimicrobial activity, whereas any of the tested techniques showed the ability to extract compounds with antioxidant capacity. In most of the cases, both plant extracts (mimosa and olive) were more efficient against S. aureus than E. coli. In the present study, both mimosa and olive leaf crude extracts proved to have antimicrobial and antioxidant activities, increasing the demand of these natural products as a source of compounds with health benefits.</jats:p

Beyond penicillin: the potential of filamentous fungi for drug discovery in the age of antibiotic resistance

Antibiotics are a staple in current medicine for the therapy of infectious diseases. However, their extensive use and misuse, combined with the high adaptability of bacteria, has dangerously increased the incidence of multi-drug-resistant (MDR) bacteria. This makes the treatment of infections challenging, especially when MDR bacteria form biofilms. The most recent antibiotics entering the market have very similar modes of action to the existing ones, so bacteria rapidly catch up to those as well. As such, it is very important to adopt effective measures to avoid the development of antibiotic resistance by pathogenic bacteria, but also to perform bioprospecting of new molecules from diverse sources to expand the arsenal of drugs that are available to fight these infectious bacteria. Filamentous fungi have a large and vastly unexplored secondary metabolome and are rich in bioactive molecules that can be potential novel antimicrobial drugs. Their production can be challenging, as the associated biosynthetic pathways may not be active under standard culture conditions. New techniques involving metabolic and genetic engineering can help boost antibiotic production. This study aims to review the bioprospection of fungi to produce new drugs to face the growing problem of MDR bacteria and biofilm-associated infections.This research was funded by LA/P/0045/2020 (ALiCE), UIDB/00511/2020, and UIDP/00511/2020 (LEPABE); funded by national funds through FCT/MCTES (PIDDAC), UIDB/04469/2020 (CEB), and LABBELS—Associate Laboratory in Biotechnology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020; Germirrad-POCI-01-0247-FEDER-072237 funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI) and by national funds (PIDDAC) through FCT/MCTES; and the FCT grant (2020.04773.BD).info:eu-repo/semantics/publishedVersio

Come out and play:Exploring bacterial cell wall synthesis and cell division

Bacteriën zijn eencellige organismen die over de hele wereld zijn verspreid. Normaal gesproken neemt de celgrootte van de bacterie toe voordat de bacteriecel opsplitst in twee identieke cellen. Voor deze bacteriële levenscyclus zijn twee verschillende, maar gerelateerde cellulaire processen nodig: de synthese en de deling van de celwand. Het celwandsynthese proces is erg belangrijk om er voor te zorgen dat de celwand goed gesynthetiseerd en georganiseerd wordt, aangezien het betrokken is bij de uiteindelijk grens en vorm van de bacterie. De synthese van de nieuwe celwand heeft verschillende eiwitten nodig die samenwerken om peptidoglycaan te maken, de belangrijkste component voor de celwand. Celwandsynthese is niet alleen nodig om de cel te laten groeien, maar ook om de cel zich goed te laten delen zonder dat de celwand breekt. Ook bij celdeling werken veel verschillende eiwitten samen, zodat uiteindelijk de cel gedeeld wordt in twee dochtercellen. Zowel de celwandsynthese als de celdeling zijn uitermate belangrijk en om die reden uitgebreid bestudeerd in de afgelopen decennia. Echter veel specifieke details zijn nog onbekend. Daarom wordt er in dit proefschrift een aantal verschillende manieren gebruikt om de complexiteit van de celwandsynthese en celdeling verder te ontrafelen. Verschillende aspecten zijn hierbij onderzocht: zowel de interne membraanorganisatie, als de chaperonne activiteit van het eiwit YidC en het antibacteriële effect van alkylgallaten. Deze studie onderstreept daarmee de nauw verweven relatie tussen de bacteriële celwandsynthese en de celdeling

Quorum sensing architecture network in Escherichia coli virulence and pathogenesis

Escherichia coli is a Gram-negative commensal bacterium of the normal microbiota of humans and animals. However, several E. coli strains are opportunistic pathogens responsible for severe bacterial infections, including gastrointestinal and urinary tract infections. Due to the emergence of multidrug-resistant serotypes that can cause a wide spectrum of diseases, E. coli is considered one of the most troublesome human pathogens worldwide. Therefore, a more thorough understanding of its virulence control mechanisms is essential for the development of new anti-pathogenic strategies. Numerous bacteria rely on a cell density-dependent communication system known as quorum sensing (QS) to regulate several bacterial functions, including the expression of virulence factors. The QS systems described for E. coli include the orphan SdiA regulator, an autoinducer-2 (AI-2), an autoinducer-3 (AI-3) system, and indole, which allow E. coli to establish different communication processes to sense and respond to the surrounding environment. This review aims to summarise the current knowledge of the global QS network in E. coli and its influence on virulence and pathogenesis. This understanding will help to improve anti-virulence strategies with the E. coli QS network in focus. This review highlights the latest findings in the field of cell-to-cell communication systems in Escherichia coli and discusses the relevance of this complicated signalling network for the virulence and pathogenesis of this bacterium

Use of phenyl isothiocyanate for biofilm prevention and control

The purpose of the present study was to assess the antibacterial activity of phenyl isothiocyanate (PITC), a synthetic isothiocyanate, on biofilms of Escherichia coli and Staphylococcus aureus. The effects of PITC on bacterial free energy of adhesion and motility were also investigated. Biofilm formation in 96-well polystyrene microtiter plates was quantified by crystal violet staining and the metabolic activity of those biofilms was assessed with alamar blue. The viability and culturability of the biofilm bacteria after exposure to PITC were determined. The highest removal and metabolic activity reduction of biofilms with PITC was around 90% for both bacteria. Treatment with PITC enabled 4.5 and 4.0 log(10) reductions of the number of viable cells for E. coli and S. aureus, respectively; and no colony forming units (CFUs) were detected. PITC also affected the adhesion process and motility of bacteria, greatly preventing biofilm formation. In conclusion, PITC enabled both biofilm prevention and control, promoting high biofilm removal and inactivation activities, suggesting that this compound is a promising disinfectant

2-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with Staphylococcus aureus Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against Biofilms

Quorum sensing (QS) plays an essential role in the production of virulence factors, in biofilm formation and antimicrobial resistance. Consequently, inhibiting QS is being considered a promising target for antipathogenic/anti-virulence therapies. This study aims to screen 2-nitrovinylfuran derivatives structurally related to Furvina (a broad-spectrum antibiotic already used for therapeutic purposes) for their effects on QS and in biofilm prevention/control. Furvina and four 2-nitrovinylfuran derivatives (compounds 1-4) were tested to assess the ability to interfere with QS of Staphylococcus aureus using bioreporter strains (S. aureus ALC1742 and ALC1743). The activity of Furvina and the most promising quorum-sensing inhibitor (QSI) was evaluated in biofilm prevention and in biofilm control (combined with fusidic acid). The biofilms were further characterized in terms of biofilm mass, viability and membrane integrity. Compound 2 caused the most significant QS inhibition with reductions between 60% and 80%. Molecular docking simulations indicate that this compound interacts preferentially with the protein hydrophobic cleft in the LytTR domain of AgrA pocket. Metabolic inactivations of 40% for S. aureus ALC1742 and 20% for S. aureus ALC1743 were reached. A 24 h-old biofilm formed in the presence of the QSI increased the metabolic inactivation by fusidic acid to 80%, for both strains. The overall results highlight the effects of compound 2 as well as the potential of combining QSI with in-use antibiotics for the management of skin and soft tissues infections