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1.
Staphylococcus aureus and Staphylococcus epidermidis are a frequent cause of biofilm-associated infections that are a tremendous burden on our healthcare system. Staphylococcal biofilms exhibit extraordinary resistance to antimicrobial killing, limiting the efficacy of antibiotic therapy, and surgical intervention is often required to remove infected tissues or implanted devices. Recent work has provided new insight into the molecular basis of biofilm development in these opportunistic pathogens. Extracellular bacterial products, environmental conditions, and polymicrobial interactions have all been shown to influence profoundly the ability of these bacteria to colonize and disperse from clinically relevant surfaces. We review new developments in staphylococcal biofilm disassembly and set them in the context of potential strategies to control biofilm infections.  相似文献   

2.
Biofilms play an important role in many chronic bacterial infections. Production of an extracellular mixture of sugar polymers called exopolysaccharide is characteristic and critical for biofilm formation. However, there is limited information about the mechanisms involved in the biosynthesis and modification of exopolysaccharide components and how these processes influence bacterial pathogenesis. Staphylococcus epidermidis is an important human pathogen that frequently causes persistent infections by biofilm formation on indwelling medical devices. It produces a poly-N-acetylglucosamine molecule that emerges as an exopolysaccharide component of many bacterial pathogens. Using a novel method based on size exclusion chromatography-mass spectrometry, we demonstrate that the surface-attached protein IcaB is responsible for deacetylation of the poly-N-acetylglucosamine molecule. Most likely due to the loss of its cationic character, non-deacetylated poly-acetylglucosamine in an isogenic icaB mutant strain was devoid of the ability to attach to the bacterial cell surface. Importantly, deacetylation of the polymer was essential for key virulence mechanisms of S. epidermidis, namely biofilm formation, colonization, and resistance to neutrophil phagocytosis and human antibacterial peptides. Furthermore, persistence of the icaB mutant strain was significantly impaired in a murine model of device-related infection. This is the first study to describe a mechanism of exopolysaccharide modification that is indispensable for the development of biofilm-associated human disease. Notably, this general virulence mechanism is likely similar for other pathogenic bacteria and constitutes an excellent target for therapeutic maneuvers aimed at combating biofilm-associated infection.  相似文献   

3.
Staphylococcus aureus biofilm infections of indwelling medical devices are a major medical challenge because of their high prevalence and antibiotic resistance. As fibrin plays an important role in S. aureus biofilm formation, we hypothesize that coating of the implant surface with fibrinolytic agents can be used as a new method of antibiofilm prophylaxis. The effect of tissue plasminogen activator (tPA) coating on S. aureus biofilm formation was tested with in vitro microplate biofilm assays and an in vivo mouse model of biofilm infection. tPA coating efficiently inhibited biofilm formation by various S. aureus strains. The effect was dependent on plasminogen activation by tPA, leading to subsequent local fibrin cleavage. A tPA coating on implant surfaces prevented both early adhesion and later biomass accumulation. Furthermore, tPA coating increased the susceptibility of biofilm infections to antibiotics. In vivo, significantly fewer bacteria were detected on the surfaces of implants coated with tPA than on control implants from mice treated with cloxacillin. Fibrinolytic coatings (e.g., with tPA) reduce S. aureus biofilm formation both in vitro and in vivo, suggesting a novel way to prevent bacterial biofilm infections of indwelling medical devices.  相似文献   

4.
Staphylococcal infections are often associated with the use of implantable medical devices. Such infections are difficult to treat because of biofilm resistance to antibiotics and are common causes of morbidity and mortality. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2x10(7) colony-forming units of bacterial strains. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and five contaminated groups that received intraperitoneal vancomycin, Pal-Lys-Lys-NH(2) and Pal-Lys-Lys-soacked graft, and vancomycin plus Pal-Lys-Lys-NH(2) or Pal-Lys-Lys-soacked graft, respectively. The infection was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro antibiotic susceptibility assay for Staphylococcus aureus biofilms was performed to elucidate the same activity. When tested alone, vancomycin and lipopeptides showed comparable efficacies. All combinations showed efficacies significantly higher than that of each single compound. Vancomycin combined to Pal-Lys-Lys-NH(2) exerted the strongest anti-staphylococcal efficacies. The in vitro studies showed, that MIC and MBC values for vancomycin were lower in presence of lipopeptides. They reduce the bacterial load and to enhance the effect of vancomycin in the prevention of vascular graft staphylococcal infections.  相似文献   

5.
Staphylococci are a major cause of infections associated with indwelling medical devices. Biofilm formation on these devices adds to the antibiotic resistance seen among clinical isolates. RNAIII-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal pathogenesis, including biofilm formation, by obstructing quorum sensing mechanisms. Bismuth ethanedithiol (BisEDT) also prevents biofilm formation at subinhibitory concentrations. RIP and BisEDT were combined to prevent infections in a rat graft model, using antibiotic sensitive and resistant strains of Staphylococcus aureus and Staphylococcus epidermidis. BisEDT, RIP, or rifampin, or their combinations reduced the graft associated bacterial load over seven days. BisEDT–RIP was the best combination, reducing bacterial load to undetectable levels. BisEDT–RIP may prove useful for coating medical devices to prevent staphylococcal infections.  相似文献   

6.
Infections associated to microbial biofilms are involved in 80% of human infections and became a challenge concerning public health. Infections related to Staphylococcus epidermidis biofilms are presently commonly associated to medical devices, increasing treatment costs for this type of infection. Alternatives to eliminate this kind of disease have been employed in screening programs using diverse marine-derived fungi source of bioactive compounds capable to combat biofilm formation. In this work was isolated the dipeptide cis-cyclo(Leucyl-Tyrosyl) from a sponge associated Penicillium sp. possessing a remarkable inhibition up to 85% of biofilm formation without interfering with bacterial growth, confirmed by scanning electron microscopy. This is the first demonstration that cis-cyclo(Leucyl-Tyrosyl) is able to specifically inhibit biofilm formation adding another aspect to the broad spectrum of bioactivities of cyclic dipeptides.  相似文献   

7.
Staphylococcus aureus and coagulase-negative staphylococci, primarily Staphylococcus epidermidis, are recognized as a major cause of nosocomial infections associated with the use of implanted medical devices. The capacity of S. epidermidis to form biofilms, allowing it to evade host immune defence mechanisms and antibiotic therapy, is considered to be crucial in colonizing the surfaces of medical implants and dissemination of infection. It has previously been demonstrated that the biofilm of a model strain S. epidermidis RP62A comprises two carbohydrate-containing moieties, a polysaccharide having a structure of a linear poly-N-acetyl-(1-->6)-beta-D-glucosamine and teichoic acid. In the present paper we show that, unlike this model strain, certain clinical isolates of coagulase-negative staphylococci produce biofilms that do not contain detectable amounts of poly-N-acetyl-(1-->6)-beta-D-glucosamine. In contrast to that of S. epidermidis RP62A, these biofilms are not detached with metaperiodate, while proteinase K causes their partial dispersal.  相似文献   

8.
Staphylococcus epidermidis and Staphylococcus aureus are currently considered two of the most important pathogens in nosocomial infections associated with catheters and other medical implants and are also the main contaminants of medical instruments. However because these species of Staphylococcus are part of the normal bacterial flora of human skin and mucosal surfaces, it is difficult to discern when a microbial isolate is the cause of infection or is detected on samples as a consequence of contamination. Rapid identification of invasive strains of Staphylococcus infections is crucial for correctly diagnosing and treating infections. The aim of the present study was to identify specific genes to distinguish between invasive and contaminating S. epidermidis and S. aureus strains isolated on medical devices; the majority of our samples were collected from breast prostheses. As a first step, we compared the adhesion ability of these samples with their efficacy in forming biofilms; second, we explored whether it is possible to determine if isolated pathogens were more virulent compared with international controls. In addition, this work may provide additional information on these pathogens, which are traditionally considered harmful bacteria in humans, and may increase our knowledge of virulence factors for these types of infections.  相似文献   

9.
Streptococcus pneumoniae (pneumococcus) is able to form biofilms in vivo and previous studies propose that pneumococcal biofilms play a relevant role both in colonization and infection. Additionally, pneumococci recovered from human infections are characterized by a high prevalence of lysogenic bacteriophages (phages) residing quiescently in their host chromosome. We investigated a possible link between lysogeny and biofilm formation. Considering that extracellular DNA (eDNA) is a key factor in the biofilm matrix, we reasoned that prophage spontaneous activation with the consequent bacterial host lysis could provide a source of eDNA, enhancing pneumococcal biofilm development. Monitoring biofilm growth of lysogenic and non-lysogenic pneumococcal strains indicated that phage-infected bacteria are more proficient at forming biofilms, that is their biofilms are characterized by a higher biomass and cell viability. The presence of phage particles throughout the lysogenic strains biofilm development implicated prophage spontaneous induction in this effect. Analysis of lysogens deficient for phage lysin and the bacterial major autolysin revealed that the absence of either lytic activity impaired biofilm development and the addition of DNA restored the ability of mutant strains to form robust biofilms. These findings establish that limited phage-mediated host lysis of a fraction of the bacterial population, due to spontaneous phage induction, constitutes an important source of eDNA for the S. pneumoniae biofilm matrix and that this localized release of eDNA favors biofilm formation by the remaining bacterial population.  相似文献   

10.
Staphylococcus epidermidis is a significant nosocomial pathogen in predisposed hosts because of its capability of forming a biofilm on indwelling medical devices. The initial stage of biofilm formation has a key role in S. epidermidis abiotic surface colonization. Recently, many strategies have been developed to create new anti-biofilm surfaces able to control bacterial adhesion mechanisms. In this work, the self-assembled amphiphilic layers formed by two fungal hydrophobins (Vmh2 and Pac3) have proven to be able to reduce the biofilm formed by different strains of S. epidermidis on polystyrene surfaces. The reduction in the biofilm thickness on the coated surfaces and the preservation of cell vitality have been demonstrated through confocal laser scanning microscope analysis. Moreover, the anti-biofilm efficiency of the self-assembled layers on different medically relevant materials has also been demonstrated using a CDC biofilm reactor.  相似文献   

11.
Biofilms are complex communities of bacteria encased in a matrix composed primarily of polysaccharides, extracellular DNA, and protein. Staphylococcus aureus can form biofilm infections, which are often debilitating due to their chronicity and recalcitrance to antibiotic therapy. Currently, the immune mechanisms elicited during biofilm growth and their impact on bacterial clearance remain to be defined. We used a mouse model of catheter-associated biofilm infection to assess the functional importance of TLR2 and TLR9 in the host immune response during biofilm formation, because ligands for both receptors are present within the biofilm. Interestingly, neither TLR2 nor TLR9 impacted bacterial density or inflammatory mediator secretion during biofilm growth in vivo, suggesting that S. aureus biofilms circumvent these traditional bacterial recognition pathways. Several potential mechanisms were identified to account for biofilm evasion of innate immunity, including significant reductions in IL-1β, TNF-α, CXCL2, and CCL2 expression during biofilm infection compared with the wound healing response elicited by sterile catheters, limited macrophage invasion into biofilms in vivo, and a skewing of the immune response away from a microbicidal phenotype as evidenced by decreases in inducible NO synthase expression concomitant with robust arginase-1 induction. Coculture studies of macrophages with S. aureus biofilms in vitro revealed that macrophages successful at biofilm invasion displayed limited phagocytosis and gene expression patterns reminiscent of alternatively activated M2 macrophages. Collectively, these findings demonstrate that S. aureus biofilms are capable of attenuating traditional host proinflammatory responses, which may explain why biofilm infections persist in an immunocompetent host.  相似文献   

12.
The role of bacterial biofilms in ocular infections   总被引:7,自引:0,他引:7  
There is increasing evidence that bacterial biofilms play a role in a variety of ocular infections. Bacterial growth is characterized as a biofilm when bacteria attach to a surface and/or to each other. This is distinguished from a planktonic or free-living mode of bacterial growth where these interactions are not present. Biofilm formation is a genetically controlled process in the life cycle of bacteria resulting in numerous changes in the cellular physiology of the organism, often including increased antibiotic resistance compared to growth under planktonic conditions. The presence of bacterial biofilms has been demonstrated on many medical devices including intravenous catheters, as well as materials relevant to the eye such as contact lenses, scleral buckles, suture material, and intraocular lenses. Many ocular infections often occur when such prosthetic devices come in contact with or are implanted in the eye. For instance, 56% of corneal ulcers in the United States are associated with contact lens wear. Bacterial biofilms may participate in ocular infections by allowing bacteria to persist on abiotic surfaces that come in contact with, or are implanted in the eye, and by direct biofilm formation on the biotic surfaces of the eye. An understanding of the role of bacterial biofilm formation in ocular infections may aid in the development of future antimicrobial strategies in ophthalmology. We review the current literature and concepts relating to biofilm formation and infections of the eye.  相似文献   

13.
The use of indwelling medical devices is rapidly growing and is often complicated by infections with biofilm-forming microbes that are resistant to antimicrobial agents and host defense mechanisms. Fungal biofilms have emerged as a clinical problem associated with these medical device infections, causing significant morbidity and mortality. This review discusses the recent advances in the understanding of fungal biofilms, including the role of fungal surface components in adherence, gene expression, and quorum sensing in biofilm formation. We propose novel strategies for the prevention or eradication of microbial colonization of medical prosthetic devices.  相似文献   

14.
Staphylococcus aureus and Staphylococcus epidermidis are recognized as the most frequent cause of biofilm-associated nosocomial and indwelling medical device infections. Biofilm-associated infections are known to be highly resistant to our current arsenal of clinically used antibiotics and antibacterial agents. To exacerbate this problem, no therapeutic option exists that targets biofilm-dependent machinery critical to Staphylococcal biofilm formation and maintenance. Here, we describe the discovery of a series of quinoline small molecules that demonstrate potent biofilm dispersal activity against methicillin-resistant S. aureus and S. epidermidis using a scaffold hopping strategy. This interesting class of quinolines also has select synthetic analogues that demonstrate potent antibacterial activity and biofilm inhibition against S. aureus and S. epidermidis.  相似文献   

15.
16.
Staphylococcus aureus is a leading cause of catheter-related bloodstream infections and endocarditis. Both involve (i) biofilm formation, (ii) exposure to fluid shear, and (iii) high rates of dissemination. We found that viscoelasticity allowed S. aureus biofilms to resist detachment due to increased fluid shear by deformation, while remaining attached to a surface. Further, we report that S. aureus microcolonies moved downstream by rolling along the lumen walls of a glass flow cell, driven by the flow of the overlying fluid. The rolling appeared to be controlled by viscoelastic tethers. This tethered rolling may be important for the surface colonization of medical devices by nonmotile bacteria.  相似文献   

17.
Biofilms play a pivotal role in medical device-related infections. However, epidemiological analysis of biofilm formation and genotyping among clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with orthopaedic infections has rarely been reported. A total of 168 MRSA strains were examined: 23 strains from patients with device-related infection (the device group); 55 from patients with device-non-related infection (the nondevice group); and 90 from asymptomatic nasal carriers (the colonization group). Pulsed-field gel electrophoresis analysis and five genotyping methods including agr typing were performed. Biofilm formation was quantified using a microtitre plate assay. The device group had a significantly higher incidence of agr-2 than the colonization group (78.3% vs. 34.4%, P=0.001). The biofilm index of the agr-2 (0.523 ± 0.572) strains was significantly higher than those of agr-1 (0.260 ± 0.418, P<0.0001) and agr-3 (0.379 ± 0.557, P=0.045). The prevalence of strong biofilm formers in the device group (43.5%) was significantly higher than that in the nondevice group (12.7%, P=0.003) and the colonization group (20.0%, P=0.020). agr-2 MRSA strains may be more likely to cause orthopaedic device infection because of their strong biofilm formation ability.  相似文献   

18.
Human respiratory syncytial virus (HRSV) and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants hospitalized with bronchiolitis or pneumonia. It has been described that respiratory virus infections may predispose for bacterial superinfections, resulting in severe disease. However, studies on the influence of bacterial colonization of the upper respiratory tract on the pathogenesis of subsequent respiratory virus infections are scarce. Here, we have investigated whether pneumococcal colonization enhances subsequent HRSV infection. We used a newly generated recombinant subgroup B HRSV strain that expresses enhanced green fluorescent protein and pneumococcal isolates obtained from healthy children in disease-relevant in vitro and in vivo model systems. Three pneumococcal strains specifically enhanced in vitro HRSV infection of primary well-differentiated normal human bronchial epithelial cells grown at air-liquid interface, whereas two other strains did not. Since previous studies reported that bacterial neuraminidase enhanced HRSV infection in vitro, we measured pneumococcal neuraminidase activity in these cultures but found no correlation with the observed infection enhancement in our model. Subsequently, a selection of pneumococcal strains was used to induce nasal colonization of cotton rats, the best available small animal model for HRSV. Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo. One S. pneumoniae strain enhanced HRSV both in vitro and in vivo, and was also associated with enhanced syncytium formation in vivo. However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact. These results demonstrate that pneumococcal colonization can enhance subsequent HRSV infection, and provide tools for additional mechanistic and intervention studies.  相似文献   

19.
Pseudomonas aeruginosa is a Gram-negative bacterial species that causes several opportunistic human infections. This organism is also found in the environment, where it is renowned (like other Pseudomonads) for its ability to use a wide variety of compounds as carbon and energy sources. It is a model species for studying group-related behaviour in bacteria. Two types of group behaviour it engages in are intercellular signalling, or quorum sensing, and the formation of surface-associated communities called biofilms. Both quorum sensing and biofilm formation are important in the pathogenesis of P. aeruginosa infections. Quorum sensing regulates the expression of several secreted virulence factors and quorum sensing mutant strains are attenuated for virulence in animal models. Biofilms have been implicated in chronic infections. Two examples are the chronic lung infections afflicting people suffering from cystic fibrosis and colonization of indwelling medical devices. This review will discuss quorum sensing and biofilm formation and studies that link these two processes.  相似文献   

20.
Staphylococcus aureus is able to disseminate from vascular device biofilms to the blood and organs, resulting in life‐threatening infections such as endocarditis. The mechanisms behind spreading are largely unknown, especially how the bacterium escapes immune effectors and antibiotics in the process. Using an in vitro catheter infection model, we studied S. aureus biofilm growth, late‐stage dispersal, and reattachment to downstream endothelial cell layers. The ability of the released biofilm material to resist host response and disseminate in vivo was furthermore studied in whole blood and phagocyte survival assays and in a short‐term murine infection model. We found that S. aureus biofilms formed in flow of human plasma release biofilm thromboemboli with embedded bacteria and bacteria‐secreted polysaccharides. The emboli disseminate as antibiotic and immune resistant vehicles that hold the ability to adhere to and initiate colonisation of endothelial cell layers under flow. In vivo experiments showed that the released biofilm material reached the heart similarly as ordinary broth‐grown bacteria but also that clumps to some extend were trapped in the lungs. The clumping dispersal of S. aureus from in vivo‐like vascular biofilms and their specific properties demonstrated here help explain the pathophysiology associated with S. aureus bloodstream infections.  相似文献   

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