#Avibactam Sensitizes #Carbapenem-Resistant #NDM-1-Producing #Klebsiella pneumoniae to Innate Immune Clearance (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Avibactam Sensitizes Carbapenem-Resistant NDM-1-Producing Klebsiella pneumoniae to Innate Immune Clearance

Erlinda R Ulloa, Nicholas Dillon, Hannah Tsunemoto, Joe Pogliano, George Sakoulas, Victor Nizet

The Journal of Infectious Diseases, jiz128, https://doi.org/10.1093/infdis/jiz128

Published: 29 March 2019

 

Abstract

Infections caused by New Delhi metallo-β-lactamases (NDM)-producing strains of multidrug-resistant (MDR) Klebsiella pneumoniae (KP) are a global public health threat lacking reliable therapies. NDM is impervious to all existing β-lactamase inhibitor (BLI) drugs, including the non-β-lactam structure BLI, avibactam (AVI). Though lacking direct activity against NDM enzymes, AVI can interact with penicillin-binding protein 2 in a manner that may influence cell wall dynamics. We found that exposure of NDM KP to AVI led to striking bactericidal interactions with human cathelicidin antimicrobial peptide LL-37, a frontline component of host innate immunity. Moreover, AVI markedly sensitized NDM KP to killing by freshly isolated human neutrophils, platelets, and serum when complement was active. Finally, AVI monotherapy reduced lung NDM KP counts in a murine pulmonary challenge model. AVI has immune sensitizing activities against NDM KP not appreciated by standard antibiotic testing and meriting further study.

New Delhi metallo-β-lactamase (NDM), Klebsiella pneumoniae, non-β-lactam-β-lactamase-inhibitors, avibactam, innate immunity, platelet, neutrophil, human serum

Topic: antibiotics – blood platelets – lung – drug clearance – cell wall – complement system proteins – immunity, natural – klebsiella pneumoniae – lactams – neutrophils – peptides – infection – enzymes – mice – public health medicine – antimicrobials – penicillin-binding proteins – ll-37 peptide – cathelicidin – killing – host (organism) – avibactam – carbapenem resistance

Issue Section: Major Article

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© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Klebsiella pneumoniae; Carbapenem; NDM1; Avibactam.

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gimi69

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

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