Dataset Information

Fostering Innovation in the Treatment of Chronic Polymicrobial Cystic Fibrosis-Associated Infections Exploring Aspartic Acid and Succinic Acid as Ciprofloxacin Adjuvants.

ABSTRACT: Cystic fibrosis (CF) disease provokes the accumulation of thick and viscous sputum in the lungs, favoring the development of chronic and polymicrobial infections. Pseudomonas aeruginosa is the main bacterium responsible for these chronic infections, and much of the difficulty involved in eradicating it is due to biofilm formation. However, this could be mitigated using adjuvant compounds that help or potentiate the antibiotic action. Therefore, the main goal of this study was to search for substances that function as adjuvants and also as biofilm-controlling compounds, preventing or dismantling P. aeruginosa biofilms formed in an in vitro CF airway environment. Dual combinations of compounds with subinhibitory (1 and 2 mg/L) and inhibitory concentrations (4 mg/L) of ciprofloxacin were tested to inhibit the bacterial growth and biofilm formation (prophylactic approach) and to eradicate 24-h-old P. aeruginosa populations, including planktonic cells and biofilms (treatment approach). Our results revealed that aspartic acid (Asp) and succinic acid (Suc) restored ciprofloxacin action against P. aeruginosa. Suc combined with 2 mg/L of ciprofloxacin (Suc-Cip) was able to eradicate bacteria, and Asp combined with 4 mg/L of ciprofloxacin (Asp-Cip) seemed to eradicate the whole 24-h-old populations, including planktonic cells and biofilms. Based on biomass depletion data, we noted that Asp induced cell death and Suc seemed somehow to block or reduce the expression of ciprofloxacin resistance. As far as we know, this kind of action had not been reported up till now. The presence of Staphylococcus aureus and Burkholderia cenocepacia did not affect the efficacy of the Asp-Cip and Suc-Cip therapies against P. aeruginosa and, also important, P. aeruginosa depletion from polymicrobial communities did not create a window of opportunity for these species to thrive. Rather the contrary, Asp and Suc also improved ciprofloxacin action against B. cenocepacia. Further studies on the cytotoxicity using lung epithelial cells indicated toxicity of Suc-Cip caused by the Suc. In conclusion, we provided evidences that Asp and Suc could be potential ciprofloxacin adjuvants to eradicate P. aeruginosa living within polymicrobial communities. Asp-Cip and Suc-Cip could be promising therapeutic options to cope with CF treatment failures.

SUBMITTER: Silva E

PROVIDER: S-EPMC7481398 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Fostering Innovation in the Treatment of Chronic Polymicrobial Cystic Fibrosis-Associated Infections Exploring Aspartic Acid and Succinic Acid as Ciprofloxacin Adjuvants.

Silva Eduarda E Monteiro Rosana R Grainha Tânia T Alves Diana D Pereira Maria Olivia MO Sousa Ana Margarida AM

Frontiers in cellular and infection microbiology 20200827

Cystic fibrosis (CF) disease provokes the accumulation of thick and viscous sputum in the lungs, favoring the development of chronic and polymicrobial infections. <i>Pseudomonas aeruginosa</i> is the main bacterium responsible for these chronic infections, and much of the difficulty involved in eradicating it is due to biofilm formation. However, this could be mitigated using adjuvant compounds that help or potentiate the antibiotic action. Therefore, the main goal of this study was to search fo ...[more]

PMID: 32974221

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Project description:BackgroundResponsible innovation in health (RIH) emphasizes the importance of developing technologies that are responsive to system-level challenges and support equitable and sustainable healthcare. To help decision-makers identify whether an innovation fulfills RIH requirements, we developed and validated an evidence-informed assessment tool comprised of 4 inclusion and exclusion criteria, 9 assessment attributes and a scoring system.MethodsWe conducted an inter-rater reliability assessment to establish the extent to which 2 raters agree when applying the RIH Tool to a diversified sample of health innovations (n=25). Following the Tool's 3-step process, sources of information were collected and cross-checked to ensure their clarity and relevance. Ratings were reported independently in a spreadsheet to generate the study's database. To measure inter-rater reliability, we used: a non-adjusted index (percent agreement), a chance-adjusted index (Gwet's AC) and the Pearson's correlation coefficient. Results of the Tool's application to the whole sample of innovations are summarized through descriptive statistics.ResultsOur findings show complete agreement for the screening criteria, "almost perfect" agreement for 7 assessment attributes, "substantial" agreement for 2 attributes and "almost perfect" agreement for the RIH overall score. A large portion of the sample obtained high scores for 6 attributes (health relevance, health inequalities, responsiveness, level and intensity of care and frugality) and low scores for 3 attributes (ethical, legal, and social issues [ELSIs], inclusiveness and eco-responsibility). At the rating step, 88% of the innovations had a sufficient number of attributes documented (≥ 7/9), but the assessment was based on sources of moderate to high quality (mean score ≥ 2 points) for 36% of the sample. While "Almost all RIH features" were present for 24% of the innovations (RIH mean score between 4.1-5.0 points), "Many RIH features" were present for 52% of the sample (3.1-4.0 points) and "Few RIH features" were present for 24% of the innovations (2.1-3.0 points).ConclusionBy confirming key aspects of the RIH Tool's reliability and applicability, our study brings its development to completion. It can be jointly put into action by innovation stakeholders who want to foster innovations with greater social, economic and environmental value.

Project description:To understand cell responses against high succinate stress, a continuous culture was performed for 9 months using a wild Escherichia coli under gradually increasing succinate stress. The final adapted strain against high succinate stress, named DST160, was able to grow with no lag phase in medium containing 1.35 M of succinate stress while wild W3110 showed more than 38 h lag phase. The maximum growth rate and growth yield of DST160 under the stress condition were 0.20 h-1 and 0.192 g-cell/g-glucose, which were 53.8 % and 12.3 % higher than those of W3110 (0.13 h-1 and 0.171 g-cell/g-glucose, respectively). A single colony of E. coli W3110 was inoculated into a 15-mL tube containing 4 mL of LB medium. After 12 h cultivation in a shaking incubator at 37℃ and 220 rpm, pre-culture (1 mL) was transferred to a 250 mL-fermentor (Mini-chemostat fermentor; Biotron Inc., Bucheon, Korea) containing 100 mL medium consisted of M9-glucose minimal medium (3 g glucose , 0.8 g NH4Cl, 0.5 g NaCl, 7.5 g Na2HPO4•2H2O, 3 g KH2PO4 with separately added trace elements of 0.2 g MgSO4•7H2O, 0.1 g CaCl2, 1 mg thiamine) per liter supplemented with 254 mmole of succinate (30 g succinic acid) per liter. The initial pH of the medium was set to be pH 7.5 by adding 6N NaOH. The fermentor was operated at 37℃, 350 rpm with air flushing (100 mL/min.). After 12 h batch mode growth, feeding and outlet pumps were turned on at flow rate of 0.167 mL/min (Dilution rate=0.1 h-1). The fresh medium reservoir (10 L) contained the same contents and pH with the initial medium. Every 10 turnover time (100 h), the reservoir was changed with the same medium composition except succinate concentration. The succinate concentration of the reservoir was gradually increased by 25.4 ~ 84.7 mM (3 ~ 10 g/L of succinic acid) at a time than previous states depending on the cell concentrations at the outlet. When the cell concentration was reduced below O.D.=0.2, succinate feeding pump was temporarily stopped to go back to the slightly lower succinate concentration. The continuous culture was performed until the steady state when succinate in the reservoir reached 1.35 M (160 g/L in succinic acid form). The final adapted cells in 100 mL culture were harvested by centrifuge and frozen rapidly in a liquid nitrogen tank for further analyses including DNA microarray. To understand the change of up/down regulations in the high-succinate adapted E. coli, total mRNAs of control cells and the adapted E. coli cells were extracted using a RNA extraction kit (RNeasy mini kit; Quiagen, Hilden, Germany), and the transcriptomes were compared using DNA microarray. Hybridization and washing were accomplished by a facility of Digital Genomics Co (Seoul, Korea). DNA microarray were scanned using an Axon GenePix 4000B Scanner (Axon Instruments, Union City, CA, USA), and the scanned images were analyzed with GenePix Pro 3.0 software to obtain gene expression ratios.

Project description:BackgroundThe social-ecological systems theory, with its unique conception of resilience (social-ecological systems & resilience, SESR), provides an operational framework that currently best meets the need for integration and adaptive governance as encouraged by the Sustainable Development Goals. SESR accounts for the complex dynamics of social-ecological systems and operationalizes transdisciplinarity by focusing on community engagement, value co-creation, decentralized leadership and social innovation. Targeting Social Innovation (SI) in the context of implementation research for vector-borne diseases (VBD) control offers a low-cost strategy to contribute to lasting and contextualized community engagement in disease control and health development in low and middle income countries of the global south. In this article we describe the processes of community engagement and transdisciplinary collaboration underpinning community-based dengue management in rural primary schools and households in two districts in Cambodia.MethodsMultiple student-led and community-based interventions have been implemented focusing on empowering education, communication for behavioral change and participatory epidemiology mapping in order to engage Cambodian communities in dengue control. We describe in particular the significance of the participatory processes that have contributed to the design of SI products that emerged following iterative consultations with community stakeholders to address the dengue problem.ResultsThe SI products that emerged following our interaction with community members are 1) adult mosquito traps made locally from solid waste collections, 2) revised dengue curriculum with hands-on activities for transformative learning, 3) guppy distribution systems led by community members, 4) co-design of dengue prevention communication material by students and community members, 5) community mapping.ConclusionsThe initiative described in this article put in motion processes of community engagement towards creating ownership of dengue control interventions tools by community stakeholders, including school children. While the project is ongoing, the project's interventions so far implemented have contributed to the emergence of culturally relevant SI products and provided initial clues regarding 1) the conditions allowing SI to emerge, 2) specific mechanisms by which it happens and 3) how external parties can facilitate SI emergence. Overall there seems to be a strong argument to be made in supporting SI as a desirable outcome of project implementation towards building adaptive capacity and resilience and to use the protocol supporting this project implementation as an operational guiding document for other VBD adaptive management in the region.

Dataset Information

Fostering Innovation in the Treatment of Chronic Polymicrobial Cystic Fibrosis-Associated Infections Exploring Aspartic Acid and Succinic Acid as Ciprofloxacin Adjuvants.

Publications

Fostering Innovation in the Treatment of Chronic Polymicrobial Cystic Fibrosis-Associated Infections Exploring Aspartic Acid and Succinic Acid as Ciprofloxacin Adjuvants.

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