Developing and Characterizing Bacteriophage for Therapeutic Use Against Carbapenem‐Resistant Enterobacteriaceae in a Multiple Drug Resistant Klebsiella pneumoniae Model

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Jordyn Michalik-Provasek ◽  
Lauren Lessor ◽  
Eleftheria Mavridou ◽  
Panagiotis Zagaliotis ◽  
Thomas Walsh ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Therapeutic Use ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Multiple Drug Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

scholarly journals Klebsiella virus UPM2146 lyses multiple drug-resistant Klebsiella pneumoniae in vitro and in vivo

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245354
Author(s):  
Omar Assafiri ◽  
Adelene Ai-Lian Song ◽  
Geok Hun Tan ◽  
Irwan Hanish ◽  
Amalia Mohd Hashim ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Zebrafish Model ◽  
Whole Genome Analysis ◽  
Narrow Host Range ◽  
Opportunistic Bacteria ◽  
Multiple Drug Resistant

Klebsiella pneumoniae are opportunistic bacteria found in the gut. In recent years they have been associated with nosocomial infections. The increased incidence of multiple drug-resistant K. pneumoniae makes it necessary to find new alternatives to treat the disease. In this study, phage UPM2146 was isolated from a polluted lake which can lyse its host K. pneumoniae ATCC BAA-2146. Observation from TEM shows that UPM2146 belongs to Caudoviriales (Order) based on morphological appearance. Whole genome analysis of UPM2146 showed that its genome comprises 160,795 bp encoding for 214 putative open reading frames (ORFs). Phylogenetic analysis revealed that the phage belongs to Ackermannviridae (Family) under the Caudoviriales. UPM2146 produces clear plaques with high titers of 1010 PFU/ml. The phage has an adsorption period of 4 min, latent period of 20 min, rise period of 5 min, and releases approximately 20 PFU/ bacteria at Multiplicity of Infection (MOI) of 0.001. UPM2146 has a narrow host-range and can lyse 5 out of 22 K. pneumoniae isolates (22.72%) based on spot test and efficiency of plating (EOP). The zebrafish larvae model was used to test the efficacy of UPM2146 in lysing its host. Based on colony forming unit counts, UPM2146 was able to completely lyse its host at 10 hours onwards. Moreover, we show that the phage is safe to be used in the treatment against K. pneumoniae infections in the zebrafish model.

scholarly journals Carbapenem-Resistant Pseudomonas aeruginosa Bacteremia: Risk Factors for Mortality and Microbiologic Treatment Failure

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Deanna J. Buehrle ◽  
Ryan K. Shields ◽  
Lloyd G. Clarke ◽  
Brian A. Potoski ◽  
Cornelius J. Clancy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pseudomonas Aeruginosa ◽  
Treatment Failure ◽  
Antimicrobial Therapy ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Active Therapy ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Multiple Drug Resistant

ABSTRACT We reviewed 37 patients treated for bacteremia due to carbapenem-resistant (CR) Pseudomonas aeruginosa. Although 65% of isolates were multiple-drug resistant, therapeutic options were available, as all were susceptible to ≥1 antibiotic. A total of 92% of patients received active antimicrobial therapy, but only 57% received early active therapy (within 48 h). Fourteen-day mortality was 19%. Microbiologic failure occurred in 29%. The Pitt bacteremia score (P = 0.046) and delayed active therapy (P = 0.027) were predictive of death and microbiologic failure, respectively.

scholarly journals Complete Genome Sequence of Klebsiella pneumoniae Strain ATCC 43816

2021 ◽  
Vol 10 (5) ◽  
Author(s):  
James A. Budnick ◽  
X. Renee Bina ◽  
James E. Bina
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Strain Atcc ◽  
Healthy Individuals ◽  
Content Type ◽  
Multiple Drug Resistant

ABSTRACT Klebsiella pneumoniae is a member of Enterobacteriaceae that causes a multitude of infections in compromised and healthy individuals. The rise of hypervirulent and multiple-drug-resistant K. pneumoniae strains has made this organism a global health threat. Here, we report the complete genome sequence of K. pneumoniae strain ATCC 43816.

scholarly journals trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zachary D. Aron ◽  
Atousa Mehrani ◽  
Eric D. Hoffer ◽  
Kristie L. Connolly ◽  
Pooja Srinivas ◽  
...  
Keyword(s):  
Oral Dose ◽  
Neisseria Gonorrhoeae ◽  
Multiple Drug ◽  
Specific Inhibition ◽  
Drug Resistant ◽  
Peptidyl Transfer ◽  
Bacterial Ribosome ◽  
Multiple Drug Resistant ◽  
Unique Site

AbstractBacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways.

scholarly journals A Bibliometric Meta-Analysis of Colistin Resistance in Klebsiella pneumoniae

Diseases ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 44
Author(s):  
Ozioma Forstinus Nwabor ◽  
Pawarisa Terbtothakun ◽  
Supayang P. Voravuthikunchai ◽  
Sarunyou Chusri
Keyword(s):  
Klebsiella Pneumoniae ◽  
Research Collaboration ◽  
Research Output ◽  
Meta Analysis ◽  
Research Articles ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
The Usa ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
Linkage Strength

Colistin is a last resort antibiotic medication for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae. In recent years, various mechanisms have been reported to mediate colistin resistance in K. pneumoniae. This study reports a bibliometric analysis of published articles retrieved from the Scopus database relating to colistin resistance in K. pneumoniae. The research trends in colistin resistance and mechanisms of resistance were considered. A total of 1819 research articles published between 1995 and 2019 were retrieved, and the results indicated that 50.19% of the documents were published within 2017–2019. The USA had the highest participation with 340 (14.31%) articles and 14087 (17.61%) citations. Classification based on the WHO global epidemiological regions showed that the European Region contributed 42% of the articles while the American Region contributed 21%. The result further indicated that 45 countries had published at least 10 documents with strong international collaborations amounting to 272 links and a total linkage strength of 735. A total of 2282 keywords were retrieved; however, 57 keywords had ≥15 occurrences with 764 links and a total linkage strength of 2388. Furthermore, mcr-1, colistin resistance, NDM, mgrB, ceftazidime-avibactam, MDR, combination therapy, and carbapenem-resistant Enterobacteriaceae were the trending keywords. Concerning funders, the USA National Institute of Health funded 9.1% of the total research articles, topping the list. The analysis indicated poor research output, collaboration, and funding from Africa and South-East Asia and demands for improvement in international research collaboration.

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