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https://www.readbyqxmd.com/read/28190396/in-vitro-screening-of-an-fda-approved-library-against-eskape-pathogens
#1
Waleed Younis, Ahmed AbdelKhalek, Abdelrahman S Mayhoub, Mohamed N Seleem
Bacterial resistance to conventional antibiotics is an increasingly serious threat to public health worldwide that requires immediate exploration and the development of novel antimicrobial compounds. Drug repurposing is an inexpensive and untapped source of new antimicrobial leads, and it holds many attractive features warranting further attention for antimicrobial drug discovery. In an effort to repurpose drugs and explore new leads in the field of antimicrobial drug discovery, we performed a whole-cell screening assay of 1,600 Food and Drug Administration (FDA) approved drugs against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae (ESKAPE) pathogens...
February 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28165020/a-potent-synthetic-inorganic-antibiotic-with-activity-against-drug-resistant-pathogens
#2
Shelby Hubick, Arumugam Jayaraman, Alexander McKeen, Shelby Reid, Jane Alcorn, John Stavrinides, Brian T Sterenberg
The acronymously named "ESKAPE" pathogens represent a group of bacteria that continue to pose a serious threat to human health, not only due to their propensity for repeated emergence, but also due to their ability to "eskape" antibiotic treatment. The evolution of multi-drug resistance in these pathogens alone has greatly outpaced the development of new therapeutics, necessitating an alternative strategy for antibiotic development that considers the evolutionary mechanisms driving antibiotic resistance. In this study, we synthesize a novel inorganic antibiotic, phosphopyricin, which has antibiotic activity against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE)...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28132897/targeting-biofilms-and-persisters-of-eskape-pathogens-with-p14kans-a-kanamycin-peptide-conjugate
#3
Mohamed F Mohamed, Anna Brezden, Haroon Mohammad, Jean Chmielewski, Mohamed N Seleem
BACKGROUND: The worldwide emergence of antibiotic resistance represents a serious medical threat. The ability of these resistant pathogens to form biofilms that are highly tolerant to antibiotics further aggravates the situation and leads to recurring infections. Thus, new therapeutic approaches that adopt novel mechanisms of action are urgently needed. To address this significant problem, we conjugated the antibiotic kanamycin with a novel antimicrobial peptide (P14LRR) to develop a kanamycin peptide conjugate (P14KanS)...
January 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28051952/antimicrobial-susceptibility-of-gram-negative-eskape-pathogens-isolated-from-hospitalized-patients-with-intra-abdominal-and-urinary-tract-infections-in-asia-pacific-countries-smart-2013-2015
#4
James A Karlowsky, Daryl J Hoban, Meredith A Hackel, Sibylle H Lob, Daniel F Sahm
Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) are responsible for increases in antimicrobial-resistant infections worldwide. We determined in vitro susceptibilities to eight parenteral antimicrobial agents using Clinical and Laboratory Standards Institute broth microdilution methodology for Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal infections (IAIs) (n=3052) and urinary tract infections (UTIs) (n=1088) in 11 Asia-Pacific countries/regions from 2013 to 2015...
January 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27986722/detection-of-eskape-bacterial-pathogens-at-the-point-of-care-using-isothermal-dna-based-assays-in-a-portable-degas-actuated-microfluidic-diagnostic-assay-platform
#5
Lars D Renner, Jindong Zan, Linda I Hu, Manuel Martinez, Pedro J Resto, Adam C Siegel, Clint Torres, Sara B Hall, Tom R Slezak, Tuan H Nguyen, Douglas B Weibel
: An estimated 1.5 billion microbial infections occur globally each year and result in ∼4.6 million deaths. A technology gap associated with commercially available diagnostic tests in remote and underdeveloped regions prevents timely pathogen identification for effective antibiotic chemotherapies for infected patients. The result is a trial-and-error approach that is limited in effectiveness, increases risk for patients while contributing to antimicrobial drug resistance, and reduces the lifetime of antibiotics...
February 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27933975/high-antibacterial-activity-of-functionalized-chemically-exfoliated-mos2
#6
Subhendu Pandit, Subbaraj Karunakaran, Sunil Kumar Boda, Bikramjit Basu, Mrinmoy De
In view of the implications of inherent resistance of pathogenic bacteria, especially ESKAPE pathogens toward most of the commercially available antibiotics and the importance of these bacteria-induced biofilm formation leading to chronic infection, it is important to develop new-generation synthetic materials with greater efficacy toward antibacterial property. In addressing this issue, this paper reports a proof-of-principle study to evaluate the potential of functionalized two-dimensional chemically exfoliated MoS2 (ce-MoS2) toward inhibitory and bactericidal property against two representative ESKAPE pathogenic strain-a Gram-positive Staphylococcus aureus (MRSA) and a Gram-negative Pseudomonas aeruginosa...
November 23, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27820797/non-classical-transpeptidases-yield-insight-into-new-antibacterials
#7
Pankaj Kumar, Amit Kaushik, Evan P Lloyd, Shao-Gang Li, Rohini Mattoo, Nicole C Ammerman, Drew T Bell, Alexander L Perryman, Trevor A Zandi, Sean Ekins, Stephan L Ginell, Craig A Townsend, Joel S Freundlich, Gyanu Lamichhane
Bacterial survival requires an intact peptidoglycan layer, a three-dimensional exoskeleton that encapsulates the cytoplasmic membrane. Historically, the final steps of peptidoglycan synthesis are known to be carried out by D,D-transpeptidases, enzymes that are inhibited by the β-lactams, which constitute >50% of all antibacterials in clinical use. Here, we show that the carbapenem subclass of β-lactams are distinctly effective not only because they inhibit D,D-transpeptidases and are poor substrates for β-lactamases, but primarily because they also inhibit non-classical transpeptidases, namely the L,D-transpeptidases, which generate the majority of linkages in the peptidoglycan of mycobacteria...
January 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/27756563/allicin-inspired-thiolated-fluoroquinolones-as-antibacterials-against-eskape-pathogens
#8
Jordan G Sheppard, Timothy E Long
Thiolated fluoroquinolones were synthesized from ciprofloxacin and evaluated for antimicrobial activity against a panel of pathogenic bacteria. Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA) exhibited the highest level of increased sensitivity toward ciprofloxacin bound with a N-propylthio substituent. Evidence was found that the antibiotics form disulfides with low molecular weight thiols in bacteria and potentiate generation of cytosolic reactive oxygen species (ROS). In final analysis, the enhanced anti-MRSA activity of thiolated fluoroquinolones was attributed to increased cell permeability and reaction with cytosolic thiols that yields an inactive disulfide metabolite and the parent drug ciprofloxacin as an inhibitor of DNA synthesis...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27620956/antibiotic-resistance-in-burkholderia-species
#9
Katherine A Rhodes, Herbert P Schweizer
The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include Burkholderia mallei and Burkholderia pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia vietnamiensis belong to the Burkholderia cepacia complex and affect mostly cystic fibrosis patients...
September 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27617798/combating-multidrug-resistant-gram-negative-bacteria-with-structurally-nanoengineered-antimicrobial-peptide-polymers
#10
Shu J Lam, Neil M O'Brien-Simpson, Namfon Pantarat, Adrian Sulistio, Edgar H H Wong, Yu-Yen Chen, Jason C Lenzo, James A Holden, Anton Blencowe, Eric C Reynolds, Greg G Qiao
With the recent emergence of reports on resistant Gram-negative 'superbugs', infections caused by multidrug-resistant (MDR) Gram-negative bacteria have been named as one of the most urgent global health threats due to the lack of effective and biocompatible drugs. Here, we show that a class of antimicrobial agents, termed 'structurally nanoengineered antimicrobial peptide polymers' (SNAPPs) exhibit sub-μM activity against all Gram-negative bacteria tested, including ESKAPE and colistin-resistant and MDR (CMDR) pathogens, while demonstrating low toxicity...
September 12, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27563036/draft-genome-sequences-of-acinetobacter-baumannii-isolates-from-wounded-military-personnel
#11
Brock A Arivett, Dave C Ream, Steven E Fiester, Destaalem Kidane, Luis A Actis
Acinetobacter baumannii is a Gram-negative bacterium capable of causing hospital-acquired infections that has been grouped with Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species as ESKAPE pathogens because of their extensive drug resistance phenotypes and increasing risk to human health. Twenty-four multidrug-resistant A. baumannii strains isolated from wounded military personnel were sequenced and annotated.
2016: Genome Announcements
https://www.readbyqxmd.com/read/27516516/draft-genome-sequences-of-pseudomonas-aeruginosa-isolates-from-wounded-military-personnel
#12
Brock A Arivett, Dave C Ream, Steven E Fiester, Destaalem Kidane, Luis A Actis
Pseudomonas aeruginosa, a Gram-negative bacterium that causes severe hospital-acquired infections, is grouped as an ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogen because of its extensive drug resistance phenotypes and effects on human health worldwide. Five multidrug resistant P. aeruginosa strains isolated from wounded military personnel were sequenced and annotated in this work.
2016: Genome Announcements
https://www.readbyqxmd.com/read/27516515/draft-genome-sequences-of-escherichia-coli-isolates-from-wounded-military-personnel
#13
Brock A Arivett, Dave C Ream, Steven E Fiester, Destaalem Kidane, Luis A Actis
Members of the Escherichia coli bacterial family have been grouped as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens because of their extensive drug resistance phenotypes and increasing threat to human health. The genomes of six extended-spectrum β-lactamase (ESBL)-producing E. coli strains isolated from wounded military personnel were sequenced and annotated.
2016: Genome Announcements
https://www.readbyqxmd.com/read/27447671/toxin-antitoxin-systems-in-clinical-pathogens
#14
REVIEW
Laura Fernández-García, Lucia Blasco, Maria Lopez, German Bou, Rodolfo García-Contreras, Thomas Wood, María Tomas
Toxin-antitoxin (TA) systems are prevalent in bacteria and archaea. Although not essential for normal cell growth, TA systems are implicated in multiple cellular functions associated with survival under stress conditions. Clinical strains of bacteria are currently causing major human health problems as a result of their multidrug resistance, persistence and strong pathogenicity. Here, we present a review of the TA systems described to date and their biological role in human pathogens belonging to the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp...
July 20, 2016: Toxins
https://www.readbyqxmd.com/read/27441208/synergistic-photothermal-and-antibiotic-killing-of-biofilm-associated-staphylococcus-aureus-using-targeted-antibiotic-loaded-gold-nanoconstructs
#15
Daniel G Meeker, Samir V Jenkins, Emily K Miller, Karen E Beenken, Allister J Loughran, Amy Powless, Timothy J Muldoon, Ekaterina I Galanzha, Vladimir P Zharov, Mark S Smeltzer, Jingyi Chen
Resistance to conventional antibiotics is a growing public health concern that is quickly outpacing the development of new antibiotics. This has led the Infectious Diseases Society of America (IDSA) to designate Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species as "ESKAPE pathogens" on the basis of the rapidly decreasing availability of useful antibiotics. This emphasizes the urgent need for alternative therapeutic strategies to combat infections caused by these and other bacterial pathogens...
April 8, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27415773/evaluation-of-low-dose-ultraviolet-light-c-for-reduction-of-select-eskape-pathogens-in-a-canine-skin-and-muscle-model
#16
Mauricio Dujowich, J Brad Case, Gary Ellison, James F X Wellehan
OBJECTIVE: This study aimed at comparing the ability of low-dose UVC, 0.05% chlorhexidine, and combined UVC with 0.05% chlorhexidine to reduce colony-forming units (CFUs) on select ESKAPE pathogens (Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecium) in a canine skin and muscle model. BACKGROUND DATA: Surgical site infections (SSIs) result in increased morbidity and cost. UVC damages DNA, rendering bacteria nonviable and does not discriminate between drug-sensitive and multi-drug-resistant organisms...
August 2016: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/27387357/antibacterial-and-anticancer-activity-of-a-series-of-novel-peptides-incorporating-cyclic-tetra-substituted-c-%C3%AE-amino-acids
#17
Rickey P Hicks
Eleven antimicrobial peptides (AMP) based on the incorporation of cyclic tetra substituted C(α) amino acids, as well as other unnatural amino acids were designed, synthesized and screened for in vitro activity against 18 strains of bacteria as well as 12 cancer cell lines. The AMPs discussed herein are derived from the following peptide sequence: Ac-GF(X)G(X)B(X)G(X)F(X)G(X)GB(X)BBBB-amide, X=any one of the following residues, A5c, A6c, Tic or Oic and B=any one of the following residues, Arg, Lys, Orn, Dpr or Dab...
September 15, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27353465/in-vitro-biological-evaluation-of-novel-broad-spectrum-isothiazolone-inhibitors-of-bacterial-type-ii-topoisomerases
#18
Cédric Charrier, Anne-Marie Salisbury, Victoria J Savage, Emmanuel Moyo, Henry Forward, Nicola Ooi, Jonathan Cheung, Richard Metzger, David McGarry, Rolf Walker, Ian R Cooper, Andrew J Ratcliffe, Neil R Stokes
OBJECTIVES: To evaluate the in vitro biological properties of a novel class of isothiazolone inhibitors of the bacterial type II topoisomerases. METHODS: Inhibition of DNA gyrase and topoisomerase IV activity was assessed using DNA supercoiling and decatenation assays. MIC and MBC were determined according to CLSI guidelines. Antibacterial combinations were assessed using a two-dimensional chequerboard MIC method. Spontaneous frequency of resistance was measured at various multiples of the MIC...
October 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27318551/considerations-and-caveats-in-anti-virulence-drug-development
#19
REVIEW
Damien Maura, Alicia E Ballok, Laurence G Rahme
As antibiotic resistance remains a major public health threat, anti-virulence therapy research is gaining interest. Hundreds of potential anti-virulence compounds have been examined, but very few have made it to clinical trials and none have been approved. This review surveys the current anti-virulence research field with a focus on the highly resistant and deadly ESKAPE pathogens, especially Pseudomonas aeruginosa. We discuss timely considerations and caveats in anti-virulence drug development, including target identification, administration, preclinical development, and metrics for success in clinical trials...
October 2016: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/27303744/simultaneous-antibiofilm-and-antiviral-activities-of-an-engineered-antimicrobial-peptide-during-virus-bacterium-coinfection
#20
Jeffrey A Melvin, Lauren P Lashua, Megan R Kiedrowski, Guanyi Yang, Berthony Deslouches, Ronald C Montelaro, Jennifer M Bomberger
Antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. Polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. Chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance. The use of engineered cationic antimicrobial peptides (eCAPs) is attractive due to the slow development of resistance to these fast-acting antimicrobials and their ability to kill multidrug-resistant clinical isolates, key elements for the success of novel antimicrobial agents...
May 2016: MSphere
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