[Advances in mechanisms of biofilm formation and drug resistance of ].
Sheng wu gong cheng xue bao = Chinese journal of biotechnology
is a common pathogenic bacterium. However, due to the abuse of antibiotics, multiple drug-resistant . (DR . ) has emerged in a large number, which seriously threatens human health. DR . usually forms biofilms by attaching on contact surfaces and secreting macromolecules including polysaccharides, proteins, and lipids, thus encasing themselves in a self-generated polymeric matrix. A biofilm provides an efficacious barrier that protects bacteria from detrimental environmental factors. Simultaneously, it protects DR . from the host immune system and attenuates the penetration and killing effects of drugs, serving as a key structure for the development of drug resistance. Therefore, gaining an in-depth understanding of the DR . biofilm is crucial for treating related infectious diseases. In this paper, we summarize recent research progress in the biofilm formation mechanism, drug resistance mechanism, and measures for inhibition and clearance of DR . and provide an outlook on the future research directions.
10.13345/j.cjb.230803
Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model.
Mihu Mircea Radu,Cabral Vitor,Pattabhi Rodney,Tar Moses T,Davies Kelvin P,Friedman Adam J,Martinez Luis R,Nosanchuk Joshua D
Antimicrobial agents and chemotherapy
Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial numbers compared to those of control biofilms in vitro and in vivo, respectively. Although both phenotypes, planktonic and biofilm-associated staphylococci, of multiple clinical strains were susceptible to NO-np, bacteria within biofilms were more resistant to killing than their planktonic counterparts. Furthermore, chitosan, a biopolymer found in the exoskeleton of crustaceans and structurally integrated into the nanoparticles, seems to add considerable antimicrobial activity to the technology. Our findings suggest promising development and translational potential of NO-np for use as a prophylactic or therapeutic against bacterial biofilms on CVCs and other medical devices.
10.1128/AAC.02020-16
Rupture of Lipid Membranes Induced by Amphiphilic Janus Nanoparticles.
Lee Kwahun,Zhang Liuyang,Yi Yi,Wang Xianqiao,Yu Yan
ACS nano
The surface coatings of nanoparticles determine their interaction with biomembranes, but studies have been limited almost exclusively to nanoparticles with a uniform surface chemistry. Although nanoparticles are increasingly made with complex surface chemistries to achieve multifunctionalities, our understanding of how a heterogeneous surface coating affects particle-biomembrane interaction has been lagging far behind. Here we report an investigation of this question in an experimental system consisting of amphiphilic "two-faced" Janus nanoparticles and supported lipid membranes. We show that amphiphilic Janus nanoparticles at picomolar concentrations induce defects in zwitterionic lipid bilayers. In addition to revealing the various effects of hydrophobicity and charge in particle-bilayer interactions, we demonstrate that the Janus geometry-the spatial segregation of hydrophobicity and charges on particle surface-causes nanoparticles to bind more strongly to bilayers and induce defects more effectively than particles with uniformly mixed surface functionalities. We combine experiments with computational simulation to further elucidate how amphiphilic Janus nanoparticles extract lipids to rupture intact lipid bilayers. This study provides direct evidence that the spatial arrangement of surface functionalities on a nanoparticle, rather than just its overall surface chemistry, plays a crucial role in determining how it interacts with biological membranes.
10.1021/acsnano.8b00759
Regulation of Virulence.
Microbiology spectrum
is a Gram-positive opportunistic pathogen that has evolved a complex regulatory network to control virulence. One of the main functions of this interconnected network is to sense various environmental cues and respond by altering the production of virulence factors necessary for survival in the host, including cell surface adhesins and extracellular enzymes and toxins. Of these regulatory systems, one of the best studied is the accessory gene regulator (), which is a quorum-sensing system that senses the local concentration of a cyclic peptide signaling molecule. This system allows to sense its own population density and translate this information into a specific gene expression pattern. Besides , this pathogen uses other two-component systems to sense specific cues and coordinates responses with cytoplasmic regulators of the SarA protein family and alternative sigma factors. These divergent regulatory systems integrate the various environmental and host-derived signals into a network that ensures optimal pathogen response to the changing conditions. This article gives an overview of the most important and best-studied regulatory systems and summarizes the functions of these regulators during host interactions. The regulatory systems discussed include the quorum-sensing system; the SaeRS, SrrAB, and ArlRS two-component systems, the cytoplasmic SarA-family regulators (SarA, Rot, and MgrA); and the alternative sigma factors (SigB and SigH).
10.1128/microbiolspec.GPP3-0031-2018
Repurposing niclosamide as a versatile antimicrobial surface coating against device-associated, hospital-acquired bacterial infections.
Gwisai Tinotenda,Hollingsworth Nisha Rosita,Cowles Sarah,Tharmalingam Nagendran,Mylonakis Eleftherios,Fuchs Beth Burgwyn,Shukla Anita
Biomedical materials (Bristol, England)
Device-associated and hospital-acquired infections remain amongst the greatest challenges in regenerative medicine. Furthermore, the rapid emergence of antibiotic resistance and lack of new classes of antibiotics has made the treatment of these bacterial infections increasingly difficult. The repurposing of Food and Drug Administration approved drugs for antimicrobial therapies is a powerful means of reducing the time and cost associated with drug discovery and development. In this work, niclosamide, a commercially available anthelmintic drug with recently identified antimicrobial properties, was found to prevent the formation of, and combat existing biofilms of, several relevant Gram-positive bacteria, namely strains of Staphylococcus aureus, including methicillin resistant S. aureus (MRSA), and Staphylococcus epidermidis, all common causes of hospital-acquired and device-associated infections. This anti-biofilm activity was demonstrated at niclosamide concentrations as low as 0.01 μg ml. We then assessed niclosamide activity as an antibacterial coating, which could potentially be applied to medical device surfaces. We developed solvent cast niclosamide coatings on a variety of surfaces common amongst medical devices including glass, titanium, stainless steel, and aluminum. Niclosamide-coated surfaces exhibited potent in vitro activity against S. aureus, MRSA, and S. epidermidis. At niclosamide surface concentrations as low as 1.6 × 10 μg mm, the coatings prevented attachment of these bacteria. The coatings also cleared bacteria inoculated suspensions at niclosamide surface concentrations of 3.1 × 10 μg mm. Hemolysis was not observed at any of the antimicrobial coating concentrations tested. We report a facile, effective means of coating devices with niclosamide to both clear and prevent biofilm formation of common bacteria encountered in hospital-acquired and device-associated infections.
10.1088/1748-605X/aa7105
SarA and not sigmaB is essential for biofilm development by Staphylococcus aureus.
Valle Jaione,Toledo-Arana Alejandro,Berasain Carmen,Ghigo Jean-Marc,Amorena Beatriz,Penadés José R,Lasa Iñigo
Molecular microbiology
Staphylococcus aureus biofilm formation is associated with the production of the polysaccharide intercellular adhesin (PIA/PNAG), the product of the ica operon. The staphylococcal accessory regulator, SarA, is a central regulatory element that controls the production of S. aureus virulence factors. By screening a library of Tn917 insertions in a clinical S. aureus strain, we identified SarA as being essential for biofilm development. Non-polar mutations of sarA in four genetically unrelated S. aureus strains decreased PIA/PNAG production and completely impaired biofilm development, both in steady state and flow conditions via an agr-independent mechanism. Accordingly, real-time PCR showed that the mutation in the sarA gene resulted in downregulation of the ica operon transcription. We also demonstrated that complete deletion of sigmaB did not affect PIA/PNAG production and biofilm formation, although it slightly decreased ica operon transcription. Furthermore, the sarA-sigmaB double mutant showed a significant decrease of ica expression but an increase of PIA/PNAG production and biofilm formation compared to the sarA single mutant. We propose that SarA activates S. aureus development of biofilm by both enhancing the ica operon transcription and suppressing the transcription of either a protein involved in the turnover of PIA/PNAG or a repressor of its synthesis, whose expression would be sigmaB-dependent.
Screening a repurposing library for potentiators of antibiotics against Staphylococcus aureus biofilms.
Van den Driessche Freija,Brackman Gilles,Swimberghe Rosalie,Rigole Petra,Coenye Tom
International journal of antimicrobial agents
Staphylococcus aureus biofilms are involved in a wide range of infections that are extremely difficult to treat with conventional antibiotic therapy. We aimed to identify potentiators of antibiotics against mature biofilms of S. aureus Mu50, a methicillin-resistant and vancomycin-intermediate-resistant strain. Over 700 off-patent drugs from a repurposing library were screened in combination with vancomycin in a microtitre plate (MTP)-based biofilm model system. This led to the identification of 25 hit compounds, including four phenothiazines among which thioridazine was the most potent. Their activity was evaluated in combination with other antibiotics both against planktonic and biofilm-grown S. aureus cells. The most promising combinations were subsequently tested in an in vitro chronic wound biofilm infection model. Although no synergistic activity was observed against planktonic cells, thioridazine potentiated the activity of tobramycin, linezolid and flucloxacillin against S. aureus biofilm cells. However, this effect was only observed in a general biofilm model and not in a chronic wound model of biofilm infection. Several drug compounds were identified that potentiated the activity of vancomycin against biofilms formed in a MTP-based biofilm model. A selected hit compound lost its potentiating activity in a model that mimics specific aspects of wound biofilms. This study provides a platform for discovering and evaluating potentiators against bacterial biofilms and highlights the necessity of using relevant in vitro biofilm model systems.
10.1016/j.ijantimicag.2016.11.023
Anti-infective therapy using species-specific activators of Staphylococcus aureus ClpP.
Nature communications
The emergence of methicillin-resistant Staphylococcus aureus isolates highlights the urgent need to develop more antibiotics. ClpP is a highly conserved protease regulated by ATPases in bacteria and in mitochondria. Aberrant activation of bacterial ClpP is an alternative method of discovering antibiotics, while it remains difficult to develop selective Staphylococcus aureus ClpP activators that can avoid disturbing Homo sapiens ClpP functions. Here, we use a structure-based design to identify (R)- and (S)-ZG197 as highly selective Staphylococcus aureus ClpP activators. The key structural elements in Homo sapiens ClpP, particularly W146 and its joint action with the C-terminal motif, significantly contribute to the discrimination of the activators. Our selective activators display wide antibiotic properties towards an array of multidrug-resistant staphylococcal strains in vitro, and demonstrate promising antibiotic efficacy in zebrafish and murine skin infection models. Our findings indicate that the species-specific activators of Staphylococcus aureus ClpP are exciting therapeutic agents to treat staphylococcal infections.
10.1038/s41467-022-34753-0
Activities of Combinations of Antistaphylococcal Antibiotics with Fusidic Acid against Staphylococcal Biofilms in Static and Dynamic Models.
Siala Wafi,Rodriguez-Villalobos Hector,Fernandes Prabhavathi,Tulkens Paul M,Van Bambeke Françoise
Antimicrobial agents and chemotherapy
Staphylococcal biofilms are a major cause of therapeutic failure, especially when caused by multiresistant strains. Oral fusidic acid is currently being redeveloped in the United States for skin, skin structure, and orthopedic infections, in which biofilms play a major role. The aim of this study was to examine the activity of fusidic acid alone or combined with other antistaphylococcal drugs against biofilms made by a reference strain and five clinical isolates of or in static and dynamic models (microtiter plates and a CDC reactor) exposed to clinically relevant concentrations. In microtiter plates, antibiotics alone were poorly active, with marked differences among strains. At concentrations mimicking the free-drug human maximum concentration of drug in serum (), the combination of fusidic acid with linezolid, daptomycin, or vancomycin resulted in increased activity against 4 to 5 strains, while the combination with doxycycline, rifampin, or moxifloxacin increased activity against 1 to 3 strains only. In the CDC reactor, biofilms were grown under constant flow and antibiotic concentrations decreased over time according to human elimination rates. A bactericidal effect was obtained when fusidic acid was combined with daptomycin or linezolid, but not with vancomycin. The higher tolerance of biofilms to antibiotics in the CDC reactor is probably attributable to the more complex architecture they adopt when growing under constant flow. Because biofilms grown in the CDC reactor are considered more similar to those developing , the data support further testing of combinations of fusidic acid with daptomycin or linezolid in models pertinent to chronic skin, skin structure, or orthopedic infections.
10.1128/AAC.00598-18
Staphylococcus quorum sensing in biofilm formation and infection.
Kong Kok-Fai,Vuong Cuong,Otto Michael
International journal of medical microbiology : IJMM
Cell population density-dependent regulation of gene expression is an important determinant of bacterial pathogenesis. Staphylococci have two quorum-sensing (QS) systems. The accessory gene regulator (agr) is genus specific and uses a post-translationally modified peptide as an autoinducing signal. In the pathogens Staphylococcus aureus and Staphylococcus epidermidis, agr controls the expression of a series of toxins and virulence factors and the interaction with the innate immune system. However, the role of agr during infection is controversial. A possible second QS system of staphylococci, luxS, is found in a variety of Gram-positive and Gram-negative bacteria. Importantly, unlike many QS systems described in Gram-negative bacteria, agr and luxS of staphylococci reduce rather than induce biofilm formation and virulence during biofilm-associated infection. agr enhances biofilm detachment by up-regulation of the expression of detergent-like peptides, whereas luxS reduces cell-to-cell adhesion by down-regulating expression of biofilm exopolysaccharide. Significant QS activity in staphylococci is observed for actively growing cells at a high cell density, such as during the initial stages of an infection and under optimal environmental conditions. In contrast, the metabolically quiescent biofilm mode of growth appears to be characterized by an overall low activity of the staphylococcal QS systems. It remains to be shown whether QS control in staphylococci represents a promising target for the development of novel antibacterial agents.
10.1016/j.ijmm.2006.01.042
Quorum-sensing regulation in staphylococci-an overview.
Le Katherine Y,Otto Michael
Frontiers in microbiology
Staphylococci are frequent human commensals and some species can cause disease. Staphylococcus aureus in particular is a dangerous human pathogen. In staphylococci, the ability to sense the bacterial cell density, or quorum, and to respond with genetic adaptations is due to one main system, which is called accessory gene regulator (Agr). The extracellular signal of Agr is a post-translationally modified peptide containing a thiolactone structure. Under conditions of high cell density, Agr is responsible for the increased expression of many toxins and degradative exoenzymes, and decreased expression of several colonization factors. This regulation is important for the timing of virulence factor expression during infection and the development of acute disease, while low activity of Agr is associated with chronic staphylococcal infections, such as those involving biofilm formation. Accordingly, drugs inhibiting Agr are being evaluated for their capacity to control acute forms of S. aureus infection.
10.3389/fmicb.2015.01174
Staphylococcal infections: mechanisms of biofilm maturation and detachment as critical determinants of pathogenicity.
Otto Michael
Annual review of medicine
Biofilm-associated infections are a significant cause of morbidity and death. Staphylococci, above all Staphylococcus aureus and S. epidermidis, are the most frequent causes of biofilm-associated infections on indwelling medical devices. Although the mechanistic basis for the agglomeration of staphylococcal cells in biofilms has been investigated in great detail, we lack understanding of the forces and molecular determinants behind the structuring of biofilms and the detachment of cellular clusters from biofilms. These processes are of key importance for the formation of vital biofilms in vivo with the capacity of bacterial dissemination to secondary sites of infection. Recent studies showed that the phenol-soluble modulins, surfactant peptides secreted by staphylococci in a quorum-sensing controlled fashion, structure biofilms in vitro and in vivo and lead to biofilm detachment with the in vivo consequence of bacterial dissemination. These findings substantiate that quorum sensing and surfactants have widespread importance for biofilm maturation processes in bacteria and establish a novel theory of the molecular determinants driving dissemination of biofilm-associated infection.
10.1146/annurev-med-042711-140023
Combined an acoustic pressure simulation of ultrasonic radiation and experimental studies to evaluate control efficacy of high-intensity ultrasound against Staphylococcus aureus biofilm.
Ultrasonics sonochemistry
This study evaluated efficacy of high-intensity ultrasound (HIU) on controlling or stimulating Staphylococcus aureus biofilm. Acoustic pressure distribution on the surface of glass slide cultivated S. aureus biofilm was first simulated as a standardized parameter to reflect sono-effect. When the power of HIU was 240 W with acoustic pressure of -1.38×10 Pa, a reasonably high clearance rate of S. aureus biofilm was achieved (96.02%). As an all-or-nothing technique, the HIU did not cause sublethal or injury of S. aureus but inactivate the cell directly. A further evaluation of HIU-induced stimulation of biofilm was conducted at a low power level (i.e. 60 W with acoustic pressure of -6.91×10 Pa). The low-power-long-duration HIU treatment promoted the formation of S. aureus biofilm and enhanced its resistance as proved by transcriptional changes of genes in S. aureus, including up-regulations of rbf, sigB, lrgA, icaA, icaD, and down-regulation of icaR. These results indicate that the choose of input power is determined during the HIU-based cleaning and processing. Otherwise, the growth of S. aureus and biofilm formation are stimulated when treats by an insufficiently high power of HIU.
10.1016/j.ultsonch.2021.105764
Visible Light-Activated Carbon Dots for Inhibiting Biofilm Formation and Inactivating Biofilm-Associated Bacterial Cells.
Dong Xiuli,Overton Christopher M,Tang Yongan,Darby Jasmine P,Sun Ya-Ping,Yang Liju
Frontiers in bioengineering and biotechnology
This study aimed to address the significant problems of bacterial biofilms found in medical fields and many industries. It explores the potential of classic photoactive carbon dots (CDots), with 2,2'-(ethylenedioxy)bis (ethylamine) (EDA) for dot surface functionalization (thus, EDA-CDots) for their inhibitory effect on biofilm formation and the inactivation of cells within established biofilm. The EDA-CDots were synthesized by chemical functionalization of selected small carbon nanoparticles with EDA molecules in amidation reactions. The inhibitory efficacy of CDots with visible light against biofilm formation was dependent significantly on the time point when CDots were added; the earlier the CDots were added, the better the inhibitory effect on the biofilm formation. The evaluation of antibacterial action of light-activated EDA-CDots against planktonic cells the cells in biofilm indicate that CDots are highly effective for inactivating planktonic cells but barely inactivate cells in established biofilms. However, when coupling with chelating agents (e.g., EDTA) to target the biofilm architecture by breaking or weakening the EPS protection, much enhanced photoinactivation of biofilm-associated cells by CDots was achieved. The study demonstrates the potential of CDots to prevent the initiation of biofilm formation and to inhibit biofilm growth at an early stage. Strategic combination treatment could enhance the effectiveness of photoinactivation by CDots to biofilm-associated cells.
10.3389/fbioe.2021.786077
Broad impact of extracellular DNA on biofilm formation by clinically isolated Methicillin-resistant and -sensitive strains of Staphylococcus aureus.
Sugimoto Shinya,Sato Fumiya,Miyakawa Reina,Chiba Akio,Onodera Shoichi,Hori Seiji,Mizunoe Yoshimitsu
Scientific reports
Staphylococcus aureus is a major causative agent for biofilm-associated infections. Inside biofilms, S. aureus cells are embedded in an extracellular matrix (ECM) composed of polysaccharide-intercellular adhesins (PIA), proteins, and/or extracellular DNA (eDNA). However, the importance of each component and the relationship among them in biofilms of diverse strains are largely unclear. Here, we characterised biofilms formed by 47 S. aureus clinical isolates. In most (42/47) of the strains, biofilm formation was augmented by glucose supplementation. Sodium chloride (NaCl)-triggered biofilm formation was more prevalent in methicillin-sensitive S. aureus (15/24) than in methicillin-resistant strain (1/23). DNase I most effectively inhibited and disrupted massive biofilms, and Proteinase K was also effective. Anti-biofilm effects of Dispersin B, which cleaves PIA, were restricted to PIA-dependent biofilms formed by specific strains and showed significant negative correlations with those of Proteinase K, suggesting independent roles of PIA and proteins in each biofilm. ECM profiling demonstrated that eDNA was present in all strains, although its level differed among strains and culture conditions. These results indicate that eDNA is the most common component in S. aureus biofilms, whereas PIA is important for a small number of isolates. Therefore, eDNA can be a primary target for developing eradication strategies against S. aureus biofilms.
10.1038/s41598-018-20485-z
New approaches to the treatment of biofilm-related infections.
Wilkins Matthew,Hall-Stoodley Luanne,Allan Raymond N,Faust Saul N
The Journal of infection
Bacteria causing chronic infections predominately grow as surface-attached, sessile communities known as biofilms. Biofilm-related infections including cystic fibrosis lung infection, chronic and recurrent otitis media, chronic wounds and implant- and catheter-associated infections, are a significant cause of morbidity and mortality and financial cost. Chronic biofilm-based infections are recalcitrant to conventional antibiotic therapy and are often unperturbed by host immune responses such as phagocytosis, despite a sustained presence of host inflammation. The diagnosis of clinically important biofilm infections is often difficult as Koch's postulates are rarely met. If treatment is required, surgical removal of the infected implant, or debridement of wound or bone, is the most efficient means of eradicating a clinically significant biofilm. New approaches to treatment are under investigation.
10.1016/j.jinf.2014.07.014
Staphylococcus aureus biofilms: recent developments in biofilm dispersal.
Lister Jessica L,Horswill Alexander R
Frontiers in cellular and infection microbiology
Staphylococcus aureus is a major cause of nosocomial and community-acquired infections and represents a significant burden on the healthcare system. S. aureus attachment to medical implants and host tissue, and the establishment of a mature biofilm, play an important role in the persistence of chronic infections. The formation of a biofilm, and encasement of cells in a polymer-based matrix, decreases the susceptibility to antimicrobials and immune defenses, making these infections difficult to eradicate. During infection, dispersal of cells from the biofilm can result in spread to secondary sites and worsening of the infection. In this review, we discuss the current understanding of the pathways behind biofilm dispersal in S. aureus, with a focus on enzymatic and newly described broad-spectrum dispersal mechanisms. Additionally, we explore potential applications of dispersal in the treatment of biofilm-mediated infections.
10.3389/fcimb.2014.00178
The influence of cell and substratum surface hydrophobicities on microbial attachment.
Liu Yu,Yang Shu-Fang,Li Yong,Xu Hui,Qin Lei,Tay Joo-Hwa
Journal of biotechnology
This study investigated the role of hydrophobic/hydrophilic interaction between bacterial and support surfaces in microbial adhesion, and a model that correlates microbial adhesion and relative cell-hydrophobicity defined as the ratio of cell-support surface hydrophobicity over cell-support hydrophilicity was derived. This model quantitatively describes how cell hydrophobic and hydrophilic interactions affect microbial adhesion, and offers deep insights into the thermodynamic mechanisms of microbial adhesion. The proposed model was verified by literature data. It appears that a high cell-hydrophobicity strongly facilitates microbial adhesion on both hydrophobic and hydrophilic support surfaces.
10.1016/j.jbiotec.2004.02.012
Bacterial biofilms and quorum sensing: fidelity in bioremediation technology.
Mangwani Neelam,Kumari Supriya,Das Surajit
Biotechnology & genetic engineering reviews
Increased contamination of the environment with toxic pollutants has paved the way for efficient strategies which can be implemented for environmental restoration. The major problem with conventional methods used for cleaning of pollutants is inefficiency and high economic costs. Bioremediation is a growing technology having advanced potential of cleaning pollutants. Biofilm formed by various micro-organisms potentially provide a suitable microenvironment for efficient bioremediation processes. High cell density and stress resistance properties of the biofilm environment provide opportunities for efficient metabolism of number of hydrophobic and toxic compounds. Bacterial biofilm formation is often regulated by quorum sensing (QS) which is a population density-based cell-cell communication process via signaling molecules. Numerous signaling molecules such as acyl homoserine lactones, peptides, autoinducer-2, diffusion signaling factors, and α-hydroxyketones have been studied in bacteria. Genetic alteration of QS machinery can be useful to modulate vital characters valuable for environmental applications such as biofilm formation, biosurfactant production, exopolysaccharide synthesis, horizontal gene transfer, catabolic gene expression, motility, and chemotaxis. These qualities are imperative for bacteria during degradation or detoxification of any pollutant. QS signals can be used for the fabrication of engineered biofilms with enhanced degradation kinetics. This review discusses the connection between QS and biofilm formation by bacteria in relation to bioremediation technology.
10.1080/02648725.2016.1196554
Micrococcal Nuclease stimulates Biofilm Formation in a Murine Implant Infection Model.
Forson Abigail M,Rosman Colin W K,van Kooten Theo G,van der Mei Henny C,Sjollema Jelmer
Frontiers in cellular and infection microbiology
Advancements in contemporary medicine have led to an increasing life expectancy which has broadened the application of biomaterial implants. As each implant procedure has an innate risk of infection, the number of biomaterial-associated infections keeps rising. causes 34% of such infections and is known as a potent biofilm producer. By secreting micrococcal nuclease is able to escape neutrophil extracellular traps by cleaving their DNA-backbone. Also, micrococcal nuclease potentially limits biofilm growth and adhesion by cleaving extracellular DNA, an important constituent of biofilms. This study aimed to evaluate the impact of micrococcal nuclease on infection persistence and biofilm formation in a murine biomaterial-associated infection-model with polyvinylidene-fluoride mesh implants inoculated with bioluminescent . or its isogenic micrococcal nuclease deficient mutant. Supported by results based on bioluminescence imaging, colony forming unit counts, and histological analysis it was found that production of micrococcal nuclease enables bacteria to evade the immune response around an implant resulting in a persistent infection. As a novel finding, histological analysis provided clear indications that the production of micrococcal nuclease stimulates to form biofilms, the presence of which extended neutrophil extracellular trap formation up to 13 days after mesh implantation. Since micrococcal nuclease production appeared vital for the persistence of biomaterial-associated infection, targeting its production could be a novel strategy in preventing biomaterial-associated infection.
10.3389/fcimb.2021.799845
'Targeting' the search: An upgraded structural and functional repository of antimicrobial peptides for biofilm studies (B-AMP v2.0) with a focus on biofilm protein targets.
Frontiers in cellular and infection microbiology
Bacterial biofilms, often as multispecies communities, are recalcitrant to conventional antibiotics, making the treatment of biofilm infections a challenge. There is a push towards developing novel anti-biofilm approaches, such as antimicrobial peptides (AMPs), with activity against specific biofilm targets. In previous work, we developed Biofilm-AMP, a structural and functional repository of AMPs for biofilm studies (B-AMP v1.0) with more than 5000 structural models of AMPs and a vast library of AMP annotations to existing biofilm literature. In this study, we present an upgraded version of B-AMP, with a focus on existing and novel bacterial biofilm targets. B-AMP v2.0 hosts a curated collection of 2502 biofilm protein targets across 473 bacterial species, with structural protein models and functional annotations from PDB, UniProt, and PubMed databases. The biofilm targets can be searched for using the name of the source organism, and function and type of protein, and results include designated Target IDs (unique to B-AMP v2.0), UniProt IDs, 3D predicted protein structures, PDBQT files, pre-defined protein functions, and relevant scientific literature. To present an example of the combined applicability of both, the AMP and biofilm target libraries in the repository, we present two case studies. In the first case study, we expand an pipeline to evaluate AMPs against a single biofilm target in the multidrug resistant, bacterial pathogen , using 3D protein-peptide docking models from previous work and Molecular Dynamics simulations (~1.2µs). In the second case study, we build an pipeline to identify candidate AMPs (using AMPs with both anti-Gram positive and anti-Gram negative activity) against two biofilm targets with a common functional annotation in and , widely-encountered bacterial co-pathogens. With its enhanced structural and functional capabilities, B-AMP v2.0 serves as a comprehensive resource for AMP investigations related to biofilm studies. B-AMP v2.0 is freely available at https://b-amp.karishmakaushiklab.com and will be regularly updated with structural models of AMPs and biofilm targets, as well as 3D protein-peptide interaction models for key biofilm-forming pathogens.
10.3389/fcimb.2022.1020391
Staphylococcal Biofilm Development: Structure, Regulation, and Treatment Strategies.
Microbiology and molecular biology reviews : MMBR
In many natural and clinical settings, bacteria are associated with some type of biotic or abiotic surface that enables them to form biofilms, a multicellular lifestyle with bacteria embedded in an extracellular matrix. and , the most frequent causes of biofilm-associated infections on indwelling medical devices, can switch between an existence as single free-floating cells and multicellular biofilms. During biofilm formation, cells first attach to a surface and then multiply to form microcolonies. They subsequently produce the extracellular matrix, a hallmark of biofilm formation, which consists of polysaccharides, proteins, and extracellular DNA. After biofilm maturation into three-dimensional structures, the biofilm community undergoes a disassembly process that leads to the dissemination of staphylococcal cells. As biofilms are dynamic and complex biological systems, staphylococci have evolved a vast network of regulatory mechanisms to modify and fine-tune biofilm development upon changes in environmental conditions. Thus, biofilm formation is used as a strategy for survival and persistence in the human host and can serve as a reservoir for spreading to new infection sites. Moreover, staphylococcal biofilms provide enhanced resilience toward antibiotics and the immune response and impose remarkable therapeutic challenges in clinics worldwide. This review provides an overview and an updated perspective on staphylococcal biofilms, describing the characteristic features of biofilm formation, the structural and functional properties of the biofilm matrix, and the most important mechanisms involved in the regulation of staphylococcal biofilm formation. Finally, we highlight promising strategies and technologies, including multitargeted or combinational therapies, to eradicate staphylococcal biofilms.
10.1128/MMBR.00026-19