scholarly journals Moroccan Propolis: A Natural Antioxidant, Antibacterial, and Antibiofilm against Staphylococcus aureus with No Induction of Resistance after Continuous Exposure

2018 ◽  
Vol 2018 ◽  
pp. 1-19 ◽  
Author(s):  
Soukaïna El-Guendouz ◽  
Smail Aazza ◽  
Badiaa Lyoussi ◽  
Vassya Bankova ◽  
Milena Popova ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Quorum Sensing ◽  
Galleria Mellonella ◽  
Antioxidant Activities ◽  
Bacterial Biofilm ◽  
Continuous Exposure ◽  
Dependent Manner ◽  
Propolis Extract ◽  
Two Samples ◽  
The Impact

This study was performed to evaluate the total phenols, flavonoids, and antioxidant activities of twenty-four propolis samples from different regions of Morocco. In addition, two samples were screened regarding the antibacterial effect against four Staphylococcus aureus strains. Gas chromatography coupled to mass spectra (GC-MS) analysis was done for propolis samples used in antibacterial tests. The minimum inhibitory and minimum bactericidal concentration (MIC, MBC) were determined. The potential to acquire the resistance after sequential exposure of bacterial strains and the impact of adaptation to propolis on virulence using the Galleria mellonella were evaluated. Additionally, the effects of propolis extract on the bacterial adherence ability and its ability to inhibit the quorum sensing activity were also examined. Among the twenty-four extracts studied, the samples from Sefrou, Outat el Haj, and the two samples marketed in Morocco were the best for scavenging DPPH, ABTS, NO, peroxyl, and superoxide radicals as well as in scavenging of hydrogen peroxide. A strong correlation was found between the amounts of phenols, flavonoids, and antioxidant activities. Propolis extract at the MIC value (0.36 mg/mL) significantly reduced (p < 0.001) the virulence potential of S. aureus ATCC 6538 and the MRSA strains without leading to the development of resistance in the sequence of continuous exposure. It was able to impair the bacterial biofilm formation. The results have revealed that sample 1 reduces violacein production in a concentration dependent manner, indicating inhibition of quorum sensing. This extract has as main group of secondary metabolites flavonoids (31.9%), diterpenes (21.5%), and phenolic acid esters (16.5%).

scholarly journals Surface charge modulation of rifampicin-loaded PLA nanoparticles to improve antibiotic delivery in Staphylococcus aureus biofilms

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
David Da Costa ◽  
Chloé Exbrayat-Héritier ◽  
Basile Rambaud ◽  
Simon Megy ◽  
Raphaël Terreux ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Surface Charge ◽  
Treatment Efficacy ◽  
Particle Migration ◽  
Bacterial Biofilm ◽  
Poly Lactic Acid ◽  
Retention Capacity ◽  
The Impact ◽  
Positively Charged ◽  
Antibiotic Delivery

Abstract Background After the golden age of antibiotic discovery, bacterial infections still represent a major challenge for public health worldwide. The biofilm mode of growth is mostly responsible for chronic infections that current therapeutics fail to cure and it is well-established that novel strategies must be investigated. Particulate drug delivery systems are considered as a promising strategy to face issues related to antibiotic treatments in a biofilm context. Particularly, poly-lactic acid (PLA) nanoparticles present a great interest due to their ability to migrate into biofilms thanks to their submicronic size. However, questions still remain unresolved about their mode of action in biofilms depending on their surface properties. In the current study, we have investigated the impact of their surface charge, firstly on their behavior within a bacterial biofilm, and secondly on the antibiotic delivery and the treatment efficacy. Results Rifampicin-loaded PLA nanoparticles were synthetized by nanoprecipitation and characterized. A high and superficial loading of rifampicin, confirmed by an in silico simulation, enabled to deliver effective antibiotic doses with a two-phase release, appropriate for biofilm-associated treatments. These nanoparticles were functionalized with poly-l-lysine, a cationic peptide, by surface coating inducing charge reversal without altering the other physicochemical properties of these particles. Positively charged nanoparticles were able to interact stronger than negative ones with Staphylococcus aureus, under planktonic and biofilm modes of growth, leading to a slowed particle migration in the biofilm thickness and to an improved retention of these cationic particles in biofilms. While rifampicin was totally ineffective in biofilms after washing, the increased retention capacity of poly-l-lysine-coated rifampicin-loaded PLA nanoparticles has been associated with a better antibiotic efficacy than uncoated negatively charged ones. Conclusions Correlating the carrier retention capacity in biofilms with the treatment efficacy, positively charged rifampicin-loaded PLA nanoparticles are therefore proposed as an adapted and promising approach to improve antibiotic delivery in S. aureus biofilms.

An Alanine-Rich Peptide Attenuates Quorum Sensing-Regulated Virulence and Biofilm Formation in Staphylococcus aureus

2019 ◽  
Vol 102 (4) ◽  
pp. 1228-1234 ◽  
Author(s):  
Raid Al Akeel ◽  
Ayesha Mateen ◽  
Rabbani Syed
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Bacterial Attachment ◽  
The Body ◽  
Dependent Manner ◽  
Virulence Determinants ◽  
Microarray Gene Expression ◽  
Concentration Dependent Manner

Abstract Background: Alanine-rich proteins/peptides (ARP), with bioactivity of up to 20 amino acid residues, can be observed by the body easily during gastrointestinal digestion. Objective: Populus trichocarpa extract’s capability to attenuate quorum sensing-regulated virulence and biofilm formation in Staphylococcus aureus is described. Methods: PT13, an ARP obtained from P. trichocarpa, was tested for its activity against S. aureus using the broth microdilution test; a crystal-violet biofilm assay was performed under a scanning electron microscope. The production of various virulence factors was estimated with PT13 treatment. Microarray gene expression profiling of PT13-treated S. aureus was conducted and compared with an untreated control. Exopolysaccharides (EPS) was estimated to observe the PT13 inhibition activity. Results: PT13 was antimicrobial toward S. aureus at different concentrations and showed a similar growth rate in the presence and absence of PT13 at concentrations ≤8 μg/mL. Biofilm production was interrupted even at low concentrations, and biofilm-related genes were down-regulated when exposed to PT13. The genes encoding cell adhesion and bacterial attachment protein were the major genes suppressed by PT13. In addition, hemolysins, clumping activity, and EPS production of S. aureus decreased after treatment in a concentration-dependent manner. Conclusions: A long-chain PT13 with effective actions that, even at low concentration levels, not only regulated the gene expression in the producer organism but also blocked the virulence gene expression in this Gram-positive human pathogen is described. Highlights: We identified a PT13 as a potential antivirulence agent that regulated production of bacterial virulence determinants (e.g., toxins, enzymes and biofilm), downwards and it may be a promising anti-virulence agent to be further developed as an anti-infective agent.

scholarly journals Horizontally Acquired Quorum-Sensing Regulators Recruited by the PhoP Regulatory Network Expand the Host Adaptation Repertoire in the Phytopathogen Pectobacterium brasiliense

mSystems ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Daniel Bellieny-Rabelo ◽  
Ntombikayise Precious Nkomo ◽  
Divine Yufetar Shyntum ◽  
Lucy Novungayo Moleleki
Keyword(s):  
Quorum Sensing ◽  
Carbohydrate Metabolism ◽  
Plant Cell ◽  
Horizontal Transfer ◽  
Regulatory Network ◽  
Host Adaptation ◽  
Secretion System ◽  
Dependent Manner ◽  
Transcriptional Pattern ◽  
The Impact

ABSTRACT In this study, we examine the impact of transcriptional network rearrangements driven by horizontal gene acquisition in PhoP and SlyA regulons using as a case study a phytopathosystem comprised of potato tubers and the soft-rot pathogen Pectobacterium brasiliense 1692 (Pb1692). Genome simulations and statistical analyses uncovered the tendency of PhoP and SlyA networks to mobilize lineage-specific traits predicted as horizontal gene transfer at late infection, highlighting the prominence of regulatory network rearrangements in this stage of infection. The evidence further supports the circumscription of two horizontally acquired quorum-sensing regulators (carR and expR1) by the PhoP network. By recruiting carR and expR1, the PhoP network also impacts certain host adaptation- and bacterial competition-related systems, seemingly in a quorum sensing-dependent manner, such as the type VI secretion system, carbapenem biosynthesis, and plant cell wall-degrading enzymes (PCWDE) like cellulases and pectate lyases. Conversely, polygalacturonases and the type III secretion system (T3SS) exhibit a transcriptional pattern that suggests quorum-sensing-independent regulation by the PhoP network. This includes an uncharacterized novel phage-related gene family within the T3SS gene cluster that has been recently acquired by two Pectobacterium species. The evidence further suggests a PhoP-dependent regulation of carbapenem- and PCWDE-encoding genes based on the synthesized products’ optimum pH. The PhoP network also controls slyA expression in planta, which seems to impact carbohydrate metabolism regulation, especially at early infection, when 76.2% of the SlyA-regulated genes from that category also require PhoP to achieve normal expression levels. IMPORTANCE Exchanging genetic material through horizontal transfer is a critical mechanism that drives bacteria to efficiently adapt to host defenses. In this report, we demonstrate that a specific plant-pathogenic species (from the Pectobacterium genus) successfully integrated a population density-based behavior system (quorum sensing) acquired through horizontal transfer into a resident stress-response gene regulatory network controlled by the PhoP protein. Evidence found here underscores that subsets of bacterial weaponry critical for colonization, typically known to respond to quorum sensing, are also controlled by PhoP. Some of these traits include different types of enzymes that can efficiently break down plant cell walls depending on the environmental acidity level. Thus, we hypothesize that PhoP’s ability to elicit regulatory responses based on acidity and nutrient availability fluctuations has strongly impacted the fixation of its regulatory connection with quorum sensing. In addition, another global gene regulator, known as SlyA, was found under the PhoP regulatory network. The SlyA regulator controls a series of carbohydrate metabolism-related traits, which also seem to be regulated by PhoP. By centralizing quorum sensing and slyA under PhoP scrutiny, Pectobacterium cells added an advantageous layer of control over those two networks that potentially enhances colonization efficiency.

scholarly journals PYED-1 Inhibits Biofilm Formation and Disrupts the Preformed Biofilm of Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 240 ◽  
Author(s):  
Adriana Vollaro ◽  
Anna Esposito ◽  
Eliana Pia Esposito ◽  
Raffaele Zarrilli ◽  
Annalisa Guaragna ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Surface Proteins ◽  
Transcriptional Analysis ◽  
Capsular Polysaccharides ◽  
Dependent Manner ◽  
Chronic Infections ◽  
Concentration Dependent Manner ◽  
Expression Of Genes

Pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1 (PYED-1), a heterocyclic corticosteroid derivative of deflazacort, exhibits broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria. Here, we investigated the effect of PYED-1 on the biofilms of Staphylococcus aureus, an etiological agent of biofilm-based chronic infections such as osteomyelitis, indwelling medical device infections, periodontitis, chronic wound infections, and endocarditis. PYED-1 caused a strong reduction in biofilm formation in a concentration dependent manner. Furthermore, it was also able to completely remove the preformed biofilm. Transcriptional analysis performed on the established biofilm revealed that PYED-1 downregulates the expression of genes related to quorum sensing (agrA, RNAIII, hld, psm, and sarA), surface proteins (clfB and fnbB), secreted toxins (hla, hlb, and lukD), and capsular polysaccharides (capC). The expression of genes that encode two main global regulators, sigB and saeR, was also significantly inhibited after treatment with PYED-1. In conclusion, PYED-1 not only effectively inhibited biofilm formation, but also eradicated preformed biofilms of S. aureus, modulating the expression of genes related to quorum sensing, surface and secreted proteins, and capsular polysaccharides. These results indicated that PYED-1 may have great potential as an effective antibiofilm agent to prevent S. aureus biofilm-associated infections.

Staphylococcus aureus adheres avidly to decellularised cardiac homograft tissue in vitro in the fibrinogen-dependent manner

2020 ◽  
Vol 30 (12) ◽  
pp. 1783-1787
Author(s):  
Bartosz Ditkowski ◽  
Kirsten Leeten ◽  
Ramadan Jashari ◽  
Elizabeth Jones ◽  
Ruth Heying
Keyword(s):  
Staphylococcus Aureus ◽  
Valve Replacement ◽  
Bacterial Adhesion ◽  
Surface Composition ◽  
Bacterial Attachment ◽  
High Morbidity ◽  
Dependent Manner ◽  
Parallel Plates ◽  
Fibrinogen Binding ◽  
The Impact

AbstractObjective:Infective endocarditis remains a severe complication associated with a high morbidity and mortality in patients after heart valve replacement. Exploration of the pathogenesis is of high demand and we, therefore, present a competent model that allows studying bacterial adherence and the role of plasma fibrinogen in this process using a new in-house designed low-volume flow chamber. Three cardiac graft tissues used for pulmonary valve replacement have been tested under shear conditions to investigate the impact of surface composition on the adhesion events.Methods:Tissue pieces of cryopreserved homograft (non-decellularised), decellularised homograft and bovine pericardium patch were investigated for fibrinogen binding. Adherence of Staphylococcus aureus to these graft tissues was studied quantitatively under flow conditions in our newly fabricated chamber based on a parallel plates’ modality. The method of counting colony-forming units was reliable and reproducible to assess the propensity of different graft materials for bacterial attachment under shear.Results:Bacterial perfusions over all plasma-precoated tissues identified cryopreserved homograft with the lowest affinity for S. aureus compared to decellularised homograft presenting a significantly higher bacterial adhesion (p < 0.05), which was linked to a more avid fibrinogen binding (p < 0.01). Bovine pericardial patch, as a reference tissue in this study, was confirmed to be the most susceptible tissue graft for the bacterial adhesion, which was in line with our previous work.Conclusion:The two studied homograft tissues showed different levels of bacterial attachment, which might be postulated by the involvement of fibrinogen in the adhesion mechanism(s) shown previously for bovine tissues.

scholarly journals New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

Marine Drugs ◽  
2018 ◽  
Vol 16 (8) ◽  
pp. 274 ◽  
Author(s):  
Anna Carbone ◽  
Barbara Parrino ◽  
Maria Cusimano ◽  
Virginia Spanò ◽  
Alessandra Montalbano ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Microbial Growth ◽  
Bacterial Biofilm ◽  
Dependent Manner ◽  
Gram Negative ◽  
Ic50 Values ◽  
Planktonic Form ◽  
New Compounds ◽  
Dose Dependent

New thiazole nortopsentin analogues were conveniently synthesized and evaluated for their activity as inhibitors of biofilm formation of relevant Gram-positive and Gram-negative pathogens. All compounds were able to interfere with the first step of biofilm formation in a dose-dependent manner, showing a selectivity against the staphylococcal strains. The most active derivatives elicited IC50 values against Staphylococcus aureus ATCC 25923, ranging from 0.40–2.03 µM. The new compounds showed a typical anti-virulence profile, being able to inhibit the biofilm formation without affecting the microbial growth in the planktonic form.

scholarly journals ω-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation

2015 ◽  
Vol 59 (4) ◽  
pp. 2223-2235 ◽  
Author(s):  
Seth M. Daly ◽  
Bradley O. Elmore ◽  
Jeffrey S. Kavanaugh ◽  
Kathleen D. Triplett ◽  
Mario Figueroa ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Quorum Sensing ◽  
Immune Cell ◽  
Solid Phase ◽  
Response Regulator ◽  
Dependent Manner ◽  
Accessory Gene ◽  
Antibiotic Resistant ◽  
Content Type

ABSTRACTAntibiotic-resistant pathogens are a global health threat. Small molecules that inhibit bacterial virulence have been suggested as alternatives or adjuncts to conventional antibiotics, as they may limit pathogenesis and increase bacterial susceptibility to host killing.Staphylococcus aureusis a major cause of invasive skin and soft tissue infections (SSTIs) in both the hospital and community settings, and it is also becoming increasingly antibiotic resistant. Quorum sensing (QS) mediated by the accessory gene regulator (agr) controls virulence factor production essential for causing SSTIs. We recently identified ω-hydroxyemodin (OHM), a polyhydroxyanthraquinone isolated from solid-phase cultures ofPenicillium restrictum, as a suppressor of QS and a compound sought for the further characterization of the mechanism of action. At concentrations that are nontoxic to eukaryotic cells and subinhibitory to bacterial growth, OHM preventedagrsignaling by all fourS. aureus agralleles. OHM inhibited QS by direct binding to AgrA, the response regulator encoded by theagroperon, preventing the interaction of AgrA with theagrP2 promoter. Importantly, OHM was efficacious in a mouse model ofS. aureusSSTI. Decreased dermonecrosis with OHM treatment was associated with enhanced bacterial clearance and reductions in inflammatory cytokine transcription and expression at the site of infection. Furthermore, OHM treatment enhanced the immune cell killing ofS. aureusin vitroin anagr-dependent manner. These data suggest that bacterial disarmament through the suppression ofS. aureusQS may bolster the host innate immune response and limit inflammation.

scholarly journals Indoor Dust as a Source of Virulent Strains of the Agents of Cryptococcosis in the Rio Negro Micro-Region of the Brazilian Amazon

2020 ◽  
Vol 8 (5) ◽  
pp. 682
Author(s):  
Fábio Brito-Santos ◽  
Luciana Trilles ◽  
Carolina Firacative ◽  
Bodo Wanke ◽  
Filipe Anibal Carvalho-Costa ◽  
...  
Keyword(s):  
Galleria Mellonella ◽  
Brazilian Amazon ◽  
Vancouver Island ◽  
Indoor Dust ◽  
Continuous Exposure ◽  
Pathogenic Potential ◽  
Rio Negro ◽  
Species Complexes ◽  
Virulent Strains ◽  
The Impact

Cryptococcosis, a potentially fatal mycosis in humans, is acquired via exposure to exogenous environmental sources. This study aimed to investigate the frequency, genetic diversity, and virulence of cryptococcal strains isolated from indoor dust in the Rio Negro micro-region of the Brazilian Amazon. A total of 8.9% of the studied houses were positive, recovering nine Cryptococcus neoformans VNI and 16 C. gattii VGII isolates, revealing an endemic pattern in domestic microenvironments. The International Society for Human and Animal Mycology (ISHAM) consensus multilocus sequence typing (MLST) scheme for the C. neoformans/C. gattii species complexes identified two sequence types (STs), ST93 and ST5, amongst C. neoformans isolates and six STs amongst C. gattii isolates, including the Vancouver Island Outbreak ST7 (VGIIa) and ST20 (VGIIb), the Australian ST5, and ST264, ST268 and ST445, being unique to the studied region. Virulence studies in the Galleria mellonella model showed that five C. gattii strains and one C. neoformans strain showed a similar pathogenic potential to the highly virulent Vancouver Island outbreak strain CDR265 (VGIIa). The findings of this study indicate that humans can be exposed to the agents of cryptococcosis via house dust, forming the basis for future studies to analyze the impact of early and continuous exposure to indoor dust on the development of subclinical or clinical infections.

scholarly journals Evolution of resistance mechanisms and biological characteristics of rifampicin-resistant Staphylococcus aureus strains selected in vitro

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chong Wang ◽  
Renchi Fang ◽  
Beibei Zhou ◽  
Xuebin Tian ◽  
Xiucai Zhang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Galleria Mellonella ◽  
Resistance Mechanisms ◽  
Fitness Cost ◽  
Rifampicin Resistance ◽  
Infection Model ◽  
Resistance Mutations ◽  
Evolution Of Resistance ◽  
The Impact

Abstract Background We aimed to determine the evolutionary pathways of rifampicin resistance in Staphylococcus aureus, and the impact of resistance mutations in the rpoB gene on fitness. Methods Three clinical strains and one reference strain were used to select for rifampicin-resistant S. aureus variants. The mutations responsible for rifampicin resistance in all of the selected isolates in vitro were investigated by polymerase chain reaction (PCR) and DNA sequencing. To compare the fitness cost of rpoB mutations against their corresponding original isolates, we performed bacterial growth curve assays, static biofilm assays, in vitro competition experiments and an infection model of Galleria mellonella larvae. Results We obtained four rifampicin-resistant S. aureus isolates that showed high levels of resistance to rifampicin with a minimal inhibitory concentration (MIC) of 128 mg/L, and all isolates had a mutation at position 481 (H481F/Y) in RpoB. A broth microdilution assay indicated that mutation of H481F/Y did not affect susceptibility to common antibacterial drugs but slightly increased the vancomycin MIC. To identify the pathways involved in the development of rifampicin resistance, 32 variants (eight mutants for each strain) and four original isolates were selected for gene sequencing. Different generations of isolates were found to harbor various mutations sites. Compared with the corresponding original isolates, an in vitro fitness assay of the variant isolates showed that growth and virulence were reduced, with a statistically significantly decreased fitness, whereas the capacity for biofilm formation was elevated. Conclusions Our findings suggested that the acquisition of rifampicin resistance in S. aureus was dynamic and was associated with a significant fitness cost.

Sign in / Sign up

Export Citation Format

Share Document