Disrupting #Membrane #Adaptation Restores In Vivo Efficacy of #Antibiotics Against #MDR #Enterococci and Potentiates Killing by Human Neutrophils (J Infect Dis., abstract)

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

Disrupting Membrane Adaptation Restores In VivoEfficacy of Antibiotics Against Multidrug-Resistant Enterococci and Potentiates Killing by Human Neutrophils

Sandra Rincon, Diana Panesso, William R Miller, Kavindra V Singh, Melissa R Cruz, Ayesha Khan, An Q Dinh, Lorena Diaz, Rafael Rios, Yousif Shamoo, Jinnethe Reyes, Truc T Tran, Danielle A Garsin, Cesar A Arias

The Journal of Infectious Diseases, jiz131, https://doi.org/10.1093/infdis/jiz131

Published: 02 April 2019

 

Abstract

Daptomycin resistance in enterococci is often mediated by the LiaFSR system that orchestrates the cell membrane (CM) stress response. Activation of LiaFSR through the response regulator LiaR generates major changes in CM function and architecture (membrane adaptive response), permitting the organism to survive the antibiotic attack. Here, using a laboratory strain of Enterococcus faecalis, we developed a novel Caenorhabditis elegans model of daptomycin therapy and showed that disrupting LiaR-mediated CM adaptation restores the in vivo activity of daptomycin. The LiaR effect was also seen in a clinical strain of DAP-resistant E. faecium using a murine model of peritonitis. Furthermore, alteration of the CM response increased the ability of human-PMNs to readily clear both E. faecalis and MDR-E. faecium. Our results provide proof-of-concept that targeting the CM adaptive response restore the in vivo activity of antibiotics, prevent resistance and enhance the ability of the innate immune system to kill infecting bacteria.

LiaR, daptomycin, Caenorhabditis elegans, PMNs, phagocytosis

Issue Section: Major Article

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Keywords: Antibiotics; Drugs Resistance; Daptomycin; Enterococcus spp.

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Giuseppe Michieli

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.