45 research outputs found

    Common trust and personal safety issues: a systematic review on the acceptability of health and social interventions for persons with lived experience of homelessness

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    Background: Persons experiencing homelessness and vulnerable housing or those with lived experience of homelessness have worse health outcomes than individuals who are stably housed. Structural violence can dramatically affect their acceptance of interventions. We carried out a systematic review to understand the factors that influence the acceptability of social and health interventions among persons with lived experience of homelessness. Methods: We searched through eight bibliographic databases and selected grey literature sources for articles that were published between 1994 and 2019. We selected primary studies that reported on the experiences of homeless populations interacting with practitioners and service providers working in permanent supportive housing, case management, interventions for substance use, income assistance, and women- and youth-specific interventions. Each study was independently assessed for its methodological quality. We used a framework analysis to identify key findings and used the GRADE-CERQual approach to assess confidence in the key findings. Findings: Our search identified 11,017 citations of which 35 primary studies met our inclusion criteria. Our synthesis highlighted that individuals were marginalized, dehumanized and excluded by their lived homelessness experience. As a result, trust and personal safety were highly valued within human interactions. Lived experience of homelessness influenced attitudes toward health and social service professionals and sometimes led to reluctance to accept interventions. Physical and structural violence intersected with low self-esteem, depression and homeless-related stigma. Positive self-identity facilitated links to long-term and integrated services, peer support, and patient-centred engagement. Conclusions: Individuals with lived experience of homelessness face considerable marginalization, dehumanization and structural violence. Practitioners and social service providers should consider anti-oppressive approaches and provide, refer to, or advocate for health and structural interventions using the principles of trauma-informed care. Accepting and respecting others as they are, without judgment, may help practitioners navigate barriers to inclusiveness, equitability, and effectiveness for primary care that targets this marginalized population

    A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity

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    Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis. This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples

    Involvement of Iron in Biofilm Formation by Staphylococcus aureus

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    Staphylococcus aureus is a human pathogen that forms biofilm on catheters and medical implants. The authors' earlier study established that 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) inhibits biofilm formation by S. aureus by preventing the initial attachment of the cells to a solid surface and reducing the production of polysaccharide intercellular adhesin (PIA). Our cDNA microarray and MALDI-TOF mass spectrometric studies demonstrate that PGG treatment causes the expression of genes and proteins that are normally expressed under iron-limiting conditions. A chemical assay using ferrozine verifies that PGG is a strong iron chelator that depletes iron from the culture medium. This study finds that adding FeSO4 to a medium that contains PGG restores the biofilm formation and the production of PIA by S. aureus SA113. The requirement of iron for biofilm formation by S. aureus SA113 can also be verified using a semi-defined medium, BM, that contains an iron chelating agent, 2, 2′-dipyridyl (2-DP). Similar to the effect of PGG, the addition of 2-DP to BM medium inhibits biofilm formation and adding FeSO4 to BM medium that contains 2-DP restores biofilm formation. This study reveals an important mechanism of biofilm formation by S. aureus SA113

    Dispersion as an Important Step in the Candida albicans Biofilm Developmental Cycle

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    Biofilms are dynamic microbial communities in which transitions between planktonic and sessile modes of growth occur interchangeably in response to different environmental cues. In the last decade, early events associated with C. albicans biofilm formation have received considerable attention. However, very little is known about C. albicans biofilm dispersion or the mechanisms and signals that trigger it. This is important because it is precisely C. albicans cells dispersed from biofilms that are the main culprits associated with candidemia and establishment of disseminated invasive disease, two of the gravest forms of candidiasis. Using a simple flow biofilm model recently developed by our group, we have performed initial investigations into the phenomenon of C. albicans biofilm dispersion, as well as the phenotypic characteristics associated with dispersed cells. Our results indicate that C. albicans biofilm dispersion is dependent on growing conditions, including carbon source and pH of the media used for biofilm development. C. albicans dispersed cells are mostly in the yeast form and display distinct phenotypic properties compared to their planktonic counterparts, including enhanced adherence, filamentation, biofilm formation and, perhaps most importantly, increased pathogenicity in a murine model of hematogenously disseminated candidiasis, thus indicating that dispersed cells are armed with a complete arsenal of “virulence factors” important for seeding and establishing new foci of infection. In addition, utilizing genetically engineered strains of C. albicans (tetO-UME6 and tetO-PES1) we demonstrate that C. albicans biofilm dispersion can be regulated by manipulating levels of expression of these key genes, further supporting the evidence for a strong link between biofilms and morphogenetic conversions at different stages of the C. albicans biofilm developmental cycle. Overall, our results offer novel and important insight into the phenomenon of C. albicans biofilm dispersion, a key part of the biofilm developmental cycle, and provide the basis for its more detailed analysis

    Quantitative analysis of the accumulation, architectural organization, detachment and reseeding of Staphylococcus aureus biofilms under physiological fluid shear conditions

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    Staphylococcus aureus is an opportunistic gram- positive pathogen responsible for a wide variety of animal and human infections. In humans, it is associated with both superficial and invasive cases of infections, including bacteremia, endocarditis, osteomyelitis, septic arthritis, keratinitis, pneumonia and catheter- related infections. The prevalence of S. aureus as a human pathogen has been attributed to its ability to form specific bonds with a wide variety of extracellular matrix ( ECM) proteins. These binding events contribute significantly to the molecular mechanisms of S. aureus virulence. Additional virulence properties incur from its capacity to colonize surfaces in organized biofilm communities and from the occurrence of secondary metastatic infections caused by bacterial cells detaching from biofilms growing under shear stress. Microbial biofilms have also been associated with the spread of community- acquired bacterial infections and the emergence of resistant bacterial variants. The treatment of biofilm- associated infections costs over $ 1 billion annually in the United States. As a result, the study and characterization of microbial biofilms is rapidly gaining interest in the scientific community. The overall ambition of this project was to investigate the effects of physiologically relevant hydrodynamic forces on the accumulation and proliferation of S. aureus biofilms onto biotic substrates. Additionally, we evaluated the ability of sodium metaperiodate to inhibit the growth of S. aureus biofilms in vitro under both static and dynamic conditions. In the course of these studies, we demonstrated that: 1) hydrodynamic forces and nutrient availability modulate the rate of growth and the internal structure of early S. aureus biofilms grown on biotic surfaces; 2) through the process of erosion, S. aureus biofilms grown under physiologically relevant hydrodynamic conditions release planktonic cells with reduced adhesion avidity to ECM proteins; 3) these eroded planktonic cells demonstrate the potential to initiate secondary biofilm formations; and 4) under hydrodynamic conditions, S. aureus biofilms can withstand antimicrobial challenges that would otherwise be detrimental to sessile cultures grown under static conditions and to individual cells grown in suspension. The current research extended our understanding of the physiological effects of fluid shear forces on the development of S. aureus biofilms. It is essential to establish the principal factors leading to the multilayered accumulation of staphylococcal biofilms in vivo in order to design alternative therapeutic approaches to treating S. aureus infections

    Mannitol and the mannitol-specific enzyme IIB subunit activate Vibrio cholerae biofilm formation.

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    International audienceVibrio cholerae is a halophilic, Gram-negative rod found in marine environments. Strains that produce cholera toxin cause the diarrheal disease cholera. V. cholerae use a highly conserved, multicomponent signal transduction cascade known as the phosphoenolpyruvate phosphotransferase system (PTS) to regulate carbohydrate uptake and biofilm formation. Regulation of biofilm formation by the PTS is complex, involving many different regulatory pathways that incorporate distinct PTS components. The PTS consists of the general components enzyme I (EI) and histidine protein (HPr) and carbohydrate-specific enzymes II. Mannitol transport by V. cholerae requires the mannitol-specific EII (EII(Mtl)), which is expressed only in the presence of mannitol. Here we show that mannitol activates V. cholerae biofilm formation and transcription of the vps biofilm matrix exopolysaccharide synthesis genes. This regulation is dependent on mannitol transport. However, we show that, in the absence of mannitol, ectopic expression of the B subunit of EII(Mtl) is sufficient to activate biofilm accumulation. Mannitol, a common compatible solute and osmoprotectant of marine organisms, is a main photosynthetic product of many algae and is secreted by algal mats. We propose that the ability of V. cholerae to respond to environmental mannitol by forming a biofilm may play an important role in habitat selection

    Two rare quinone-type metabolites from the fungus Septofusidium berolinense and their biological activities

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    WOS: 000371464700006PubMed ID: 26328933TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S361]; EBILTEMEge University [2012/BIL/028]The authors are grateful to TUBITAK (109S361) and EBILTEM (2012/BIL/028) for financial support
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