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A Rapid Unraveling of the Activity and Antibiotic Susceptibility of Mycobacteria.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Mustazzolu, A 
Venturelli, L 
Dinarelli, S 
Brown, K 
Floto, RA 

Abstract

The development of antibiotic-resistant bacteria is a worldwide health-related emergency that calls for new tools to study the bacterial metabolism and to obtain fast diagnoses. Indeed, the conventional analysis time scale is too long and affects our ability to fight infections. Slowly growing bacteria represent a bigger challenge, since their analysis may require up to months. Among these bacteria, Mycobacterium tuberculosis, the causative agent of tuberculosis, has caused more than 10 million new cases and 1.7 million deaths in 2016 only. We employed a particularly powerful nanomechanical oscillator, the nanomotion sensor, to characterize rapidly and in real time tuberculous and nontuberculous bacterial species, Mycobacterium bovis bacillus Calmette-Guérin and Mycobacterium abscessus, respectively, exposed to different antibiotics. Here, we show how high-speed and high-sensitivity detectors, the nanomotion sensors, can provide a rapid and reliable analysis of different mycobacterial species, obtaining qualitative and quantitative information on their responses to different drugs. This is the first application of the technique to tackle the urgent medical issue of mycobacterial infections, evaluating the dynamic response of bacteria to different antimicrobial families and the role of the replication rate in the resulting nanomotion pattern. In addition to a fast analysis, which could massively benefit patients and the overall health care system, we investigated the real-time responses of the bacteria to extract unique information on the bacterial mechanisms triggered in response to antibacterial pressure, with consequences both at the clinical level and at the microbiological level.

Description

Keywords

antibiotic response, collective movements, fast characterization, metabolic activity, mycobacteria, nanomotion sensor, susceptibility

Journal Title

Antimicrobial Agents and Chemotherapy

Conference Name

Journal ISSN

1098-6596
1098-6596

Volume Title

63

Publisher

American Society for Microbiology
Sponsorship
Cystic Fibrosis Trust (SRC 010)
Fondation Botnar (Project 603)
G.L., S.D., and M.G. were funded by the Consiglio Nazionale delle Ricerche, short-term mobility program no. CUP B53C17001680005. S.K., G.D., and L.V. were funded by the Swiss National Grants 200021-144321 and 407240_167137, the Gebert Rüf Stiftung GRS-024/14, and NASA NNH16ZDA001N-CLDTCH.