Peptide-based efflux pump inhibitors of the small multidrug resistance protein from Pseudomonas aeruginosa.

Peptide-based efflux pump inhibitors of the small multidrug resistance protein from Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2019 Jun 17;: Authors: Mitchell CJ, Stone TA, Deber CM Abstract Bacteria have acquired multiple mechanisms to evade the lethal effects of current therapeutics, hindering treatment of bacterial infections such as the pathogen P. aeruginosa, which is responsible for nosocomial and cystic fibrosis lung infections. One resistance mechanism involves membrane-embedded multidrug efflux pumps that can effectively extrude an array of substrates, including common antibiotics, dyes, and biocides. Among these is the small multidrug resistant (SMR) efflux protein, consisting of four transmembrane helices (TMs), that functions as an antiparallel dimer. TMs 1-3 comprise the substrate binding pocket, while TM4 contains a GG7 heptad sequence motif that mediates the SMR TM4-TM4 dimerization. In the present work, we synthesized a series of peptides containing the residues centered on the TM4-TM4 binding interface found in the P. aeruginosa SMR (PAsmr), typified by Ac-Ala-(Sar)3-LLGIGLIIAGVLV-KKK-NH2 (helix-helix interaction residues underlined). Here, the acetylated N-terminal sarcosine (N-methyl-Gly) tag promotes membrane penetration, while the C-terminal Lys tag promotes selectivity for the negatively-charged bacterial membranes. This peptide was observed to competitively disrupt PAsmr-mediated efflux, as measured by efflux inhibition o...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research

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The U.S. Food and Drug Administration approved Vertex Pharmaceuticals Inc's combination treatment for a rare condition called cystic fibrosis, the agency said on Monday.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
Boston-based Vertex Pharmaceuticals Inc. has achieved one of the biggest feats to date for cystic fibrosis patients — a treatment that could benefit 90 percent of patients with the rare lung disease. The FDA approved a combination of three drugs Monday called Trikafta, which targets a mutation in the F508del gene. That genetic error is found in approximately 90 percent of patients with the rare lung disease. The drug is set to be a blockbuster product for Vertex, which makes billions annually…
Source: bizjournals.com Health Care:Pharmaceuticals headlines - Category: Pharmaceuticals Authors: Source Type: news
CONCLUSION: A substantial proportion of infants diagnosed with CF after detection by NBS already showed evidence of lung disease. P. aeruginosa colonization was associated with increas ed Bhalla scores, highlighting the importance of this CF pathogen in early structural lung disease. The presence of bronchial wall thickening at such a young age may reflect the presence of airway inflammatory processes. The detection and quantification of structural abnormalities with the modified Bhalla score may aid in the identification of lung disease before it is clinically apparent.
Source: Clinics - Category: General Medicine Source Type: research
Review clinical reference information, guidelines, and medical news on cystic fibrosis--cystic fibrosis symptoms and cystic fibrosis treatment. Review causes of cystic fibrosis and cystic fibrosis carrier information.
Source: Medscape Today Headlines - Category: Consumer Health News Tags: Resource Center Source Type: news
Authors: Martín Hidalgo-Barquero MV, Ruiz-Calero Cendrero RM, Cancho Castellano B, Cid Parra MC, Galán González J PMID: 31627973 [PubMed - as supplied by publisher]
Source: Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia - Category: Urology & Nephrology Tags: Nefrologia Source Type: research
Authors: Raman JD PMID: 31629444 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
Authors: Davaro F, May A, McFerrin C, Raza SJ, Siddiqui S, Hamilton Z Abstract INTRODUCTION: To evaluate the overall survival and pathologic downstaging effect of neoadjuvant chemotherapy for upper tract urothelial cell carcinoma. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried for patients with stage II-IV upper tract urothelial cell carcinoma undergoing definitive surgical resection (nephroureterectomy) from 2004-2015. Patients with metastatic disease were excluded. Cohorts were stratified by receipt of neoadjuvant chemotherapy (NAC). Kaplan-Meier analysis and Cox regression were used t...
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
Condition:   Cystic Fibrosis Interventions:   Behavioral: Focus group;   Behavioral: Individual interview Sponsor:   Assistance Publique - Hôpitaux de Paris Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Cosmeri Rizzato1, Javier Torres2, Elena Kasamatsu3, Margarita Camorlinga-Ponce2, Maria Mercedes Bravo4, Federico Canzian5 and Ikuko Kato6* 1Department of Translation Research and of New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy 2Unidad de Investigación en Enfermedades Infecciosas, Unidades Médicas de Alta Especialidad Pediatría, Instituto Mexicano del Seguro Social, Mexico City, Mexico 3Instituto de Investigaciones en Ciencias de la Salud, National University of Asunción, Asunción, Paraguay 4Grupo de Investigación en Biología del C&aacut...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Raquel Ferrer-Espada1,2, Xiaojing Liu1,2, Xueping Sharon Goh1,2 and Tianhong Dai1,2* 1Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States 2Vaccine &Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States Polymicrobial biofilms, in which mixed microbial species are present, play a significant role in persistent infections. Furthermore, polymicrobial biofilms promote antibiotic resistance by allowing interspecies transfer of antibiotic resistance genes. In the present study, we investigated the effec...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
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