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A new rapid and reliable bacterial phenotypic diagnostic technique detecting bacterial susceptibility to antibiotics using optical fibers

English title A new rapid and reliable bacterial phenotypic diagnostic technique detecting bacterial susceptibility to antibiotics using optical fibers
Applicant Kasas Sandor
Number 167137
Funding scheme NRP 72 Antimicrobial Resistance
Research institution Laboratoire de physique de la matière vivante EPFL - SB - IPSB - LPMV
Institution of higher education EPF Lausanne - EPFL
Main discipline Medical Microbiology
Start/End 01.03.2017 - 30.06.2021
Approved amount 453'608.00
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All Disciplines (3)

Discipline
Medical Microbiology
Infectious Diseases
Biophysics

Keywords (5)

optical fiber; Fast diagnostic methods; antibiogram; antibiotics resistance; phenotype

Lay Summary (German)

Lead
Wir entwickeln ein neues Testgerät, das bakterielle Resistenzen mit Hilfe von Glasfasern und eines Laserstrahls erkennt. Damit wollen wir die Zeit, die zwischen der Patientenaufnahme und dem Start der geeigneten Therapie verstreicht, von aktuell 24 auf 10 Stunden verkürzen.
Lay summary

Unsere Methode basiert auf der Verwendung von haarfeinen Glasfasern, auf welche die zu testenden Bakterien lebend fixiert werden. Ihre Bewegungen übertragen sich auf die Fasern, deren Vibrationen wir mit einem Laser erfassen und am Computerbildschirm darstellen. Ist ein Bakterium sensibel auf ein zugegebenes Antibiotikum, stirbt es ab, und die Glasfaser hört nach rund zehn bis zwanzig Minuten auf sich zu bewegen. Erfasst der Laser andrerseits auch nach dieser Zeit noch Bewegungen, ist das Bakterium gegen das verabreichte Antibiotikum resistent. Die Vorteile unserer Methode gegenüber gängigen Tests liegen in der kurzen Dauer bis zum Vorliegen des Resultats und in der Möglichkeit, mit mehreren Glasfasern parallel verschiedene Antibiotika zu testen.

Hintergrund
Antibiotikaresistente Bakterien vermehren sich unter anderem, weil Patienten ohne genaue Kenntnis des Bakterienstamms behandelt werden. Um jedoch von Beginn weg eine gezielte Therapie einzusetzen, die auf der kompletten Charakterisierung des vorliegenden Erregers gründet, bedarf es neuer Tests, welche die Zeit zwischen Patientenaufnahme und Therapiebeginn deutlich verkürzen. Damit eröffnen sich neue Möglichkeiten, wie etwa der Einsatz spezifischer Antibiotika anstelle von Breitbandantibiotika.

Ziel
Nebst ihrem rein medizinischen Nutzen soll unsere Technologie in verschiedener Hinsicht konkurrenzfähig sein: Wir wollen im Vergleich zu aktuellen Standards schnellere und umfangreichere Informationen erhalten, gegenüber welchen Antibiotika ein Erreger resistent ist, und dies zu gleichen bis tieferen Kosten.

Bedeutung
Unser neues Testgerät eignet sich für die Analyselabors von Spitälern, da für die Bedienung der Technik technisch geschultes Personal unabdingbar ist. Längerfristig soll der Test allerdings breiter eingesetzt werden, auch in Arztpraxen, was durch die Verwendung von günstigen Glasfasern und der Vereinfachung der Technologie möglich ist.

Direct link to Lay Summary Last update: 05.12.2017

Lay Summary (French)

Lead
Nous développons un nouvel outil qui détecte la résistance des bactéries aux antibiotiques à l'aide des fibres optiques et d'un faisceau laser. Nous voulons réduire le temps entre la prise en charge du patient et le début d’une thérapie appropriée à 10 heures au lieu des 24 heures actuelles.
Lay summary

Notre outil est basé sur des petites fibres optiques, fines autant qu’un cheveu, sur les quelles on attache les bactéries. Les bactéries vivantes transmettent leurs mouvements à la fibre, qui par conséquent vibre. Par le biais d’un faisceau laser ces mouvements sont affichés sur un ordinateur. Si la bactérie est sensible au traitement antibiotique, ces mouvements s’arrêtent dans un délai de 10-20 minutes. Au contraire, si les mouvements de la fibre continue, on est en présence d’une bactérie résistante aux antibiotiques. L’avantage de notre outil consiste dans la rapidité de mesure et aussi dans la possibilité d’utiliser plusieurs fibres optiques en parallèle afin de tester la bactérie avec des antibiotiques différents de manière simultanée.

Contexte
L’augmentation des souches de bactéries résistantes aux antibiotiques est en partie due au manque de connaissance de la souche qui infecte le patient. En réduisant le délai entre la prise en charge du patient et le début d’une thérapie ciblée basée sur une caractérisation complète de la bactérie ouvre des nouvelles voies thérapeutiques comme par exemple l’utilisation d’antibiotiques spécifiques dès le début du traitement au lieu d’antibiotiques à large spectre d’action.

Objectif
Mises à part les motivations médicales, il faut veiller qu’une nouvelle technologie soit concurrentielle sur plusieurs niveaux par rapport aux méthodes de référence actuelles. Notre outil doit être plus rapide, plus performant sur le plan des informations livrées (entre autres, test englobant un nombre grand d’antibiotiques différents, données quantitatives des concentrations critiques d’antibiotiques) et avec des coûts comparables ou moindre des standard actuels.

Importance
Ce nouvel outil est prévu pour des laboratoires d’analyse des hôpitaux où la présence de personnel technique pouvant maîtriser la technique est essentielle.

Direct link to Lay Summary Last update: 05.12.2017

Lay Summary (English)

Lead
We are developing a new test instrument that identifies bacterial resistance by means of glass fibres and a laser beam. Our aim is to shorten the time between a patient being admitted and the start of appropriate therapy from the current 24 to 10 hours.
Lay summary

Our method is based on the use of hair-thin glass fibres to which the live bacteria being tested are fixed. Their movements are transmitted to the fibres, the vibrations of which are recorded by a laser and visualised on a computer screen. If a bacterium is susceptible to an added antibiotic, it dies and the glass fibre stops moving after about 10 to 20 minutes. If, on the other hand, the laser is still detecting movement after this time has elapsed, then the bacterium is resistant to the antibiotic that has been administered. The advantages of our method compared with conventional tests are the rapid availability of the result and the possibility of testing different antibiotics in parallel by using several glass fibres.

Background
One of the reasons why antibiotic-resistant bacteria multiply is that patients are treated without doctors knowing exactly which bacterial strain is involved. If, however, targeted treatment based on full characterisation of the pathogen is to be given from the outset, new tests are needed that can shorten the time between patients being admitted and treatment being initiated. This will open up new options, such as the use of specific antibiotics instead of broad-spectrum antibiotics.

Aim
In addition to the purely medical benefit, our technology will be competitive in a number of ways: compared with current standards, we want to obtain faster and more comprehensive information on the antibiotics to which a pathogen is resistant and to do so at the same or lower cost.

Relevance
Our new test device is suitable for analytical laboratories in hospitals because the technology can only be operated by technically trained staff. In the longer term, however, the intention is to make the test available for wider use, including in doctors’ practices, by using low-cost glass fibres and simplifying the technology.

Direct link to Lay Summary Last update: 05.12.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Nanomotion Spectroscopy as a New Approach to Characterize Bacterial Virulence
Villalba Maria I., Venturelli Leonardo, Willaert Ronnie, Vela Maria E., Yantorno Osvaldo, Dietler Giovanni, Longo Giovanni, Kasas Sandor (2021), Nanomotion Spectroscopy as a New Approach to Characterize Bacterial Virulence, in Microorganisms, 9(8), 1545-1545.
Nano-Motion Analysis for Rapid and Label Free Assessing of Cancer Cell Sensitivity to Chemotherapeutics
Stupar Petar, Podolski-Renić Ana, Villalba Maria Ines, Dragoj Miodrag, Jovanović Stojanov Sofija, Pešić Milica, Kasas Sandor (2021), Nano-Motion Analysis for Rapid and Label Free Assessing of Cancer Cell Sensitivity to Chemotherapeutics, in Medicina, 57(5), 446-446.
Nanomotion Detection-Based Rapid Antibiotic Susceptibility Testing
Kasas Sandor, Malovichko Anton, Villalba Maria Ines, Vela María Elena, Yantorno Osvaldo, Willaert Ronnie G. (2021), Nanomotion Detection-Based Rapid Antibiotic Susceptibility Testing, in Antibiotics, 10(3), 287-287.
Environmental Control of Amyloid Polymorphism by Modulation of Hydrodynamic Stress
Zhou Jiangtao, Venturelli Leonardo, Keiser Ludovic, Sekatskii Sergey K., Gallaire François, Kasas Sandor, Longo Giovanni, Knowles Tuomas P. J., Ruggeri Francesco S., Dietler Giovanni (2021), Environmental Control of Amyloid Polymorphism by Modulation of Hydrodynamic Stress, in ACS Nano, 15(1), 944-953.
A perspective view on the nanomotion detection of living organisms and its features
Venturelli Leonardo, Kohler Anne‐Céline, Stupar Petar, Villalba Maria I., Kalauzi Aleksandar, Radotic Ksenija, Bertacchi Massimiliano, Dinarelli Simone, Girasole Marco, Pešić Milica, Banković Jasna, Vela Maria E., Yantorno Osvaldo, Willaert Ronnie, Dietler Giovanni, Longo Giovanni, Kasas Sandor (2020), A perspective view on the nanomotion detection of living organisms and its features, in Journal of Molecular Recognition, 33(12), 1-14.
Single yeast cell nanomotions correlate with cellular activity
Willaert Ronnie G., Vanden Boer Pieterjan, Malovichko Anton, Alioscha-Perez Mitchel, Radotić Ksenija, Bartolić Dragana, Kalauzi Aleksandar, Villalba Maria Ines, Sanglard Dominique, Dietler Giovanni, Sahli Hichem, Kasas Sandor (2020), Single yeast cell nanomotions correlate with cellular activity, in Science Advances, 6(26), eaba3139-eaba3139.
Adaptation of Pseudomonas aeruginosa to constant sub-inhibitory concentrations of quaternary ammonium compounds
Voumard Margaux, Venturelli Leonardo, Borgatta Myriam, Croxatto Antony, Kasas Sandor, Dietler Giovanni, Breider Florian, von Gunten Urs (2020), Adaptation of Pseudomonas aeruginosa to constant sub-inhibitory concentrations of quaternary ammonium compounds, in Environmental Science: Water Research & Technology, 6(4), 1139-1152.
Yeast Nanometric Scale Oscillations Highlights Fibronectin Induced Changes in C. albicans
Kannan Abhilash, Sanglard Dominique, Dietler Giovanni, Willaert Ronnie, Kasas Sandor, Kohler Anne-Céline, Venturelli Leonardo (2020), Yeast Nanometric Scale Oscillations Highlights Fibronectin Induced Changes in C. albicans, in Fermentation, 6(1), 28-28.
Silver Nanomaterials in Contemporary Molecular Physiology Research
Pantic Igor, Sarenac David, Cetkovic Mila, Milisavljevic Milan, Rakocevic Rastko, Kasas Sandor (2020), Silver Nanomaterials in Contemporary Molecular Physiology Research, in Current Medicinal Chemistry, 27(3), 411-422.
Advanced technological tools to study multidrug resistance in cancer
Andrei Luca, Kasas Sandor, Ochoa Garrido Ignacio, Stanković Tijana, Suárez Korsnes Mónica, Vaclavikova Radka, Assaraf Yehuda G., Pešić Milica (2020), Advanced technological tools to study multidrug resistance in cancer, in Drug Resistance Updates, 48, 100658-100658.
Nanomotion detection based on atomic force microscopy cantilevers
Kohler A.C., Venturelli L., Longo G., Dietler G., Kasas S. (2019), Nanomotion detection based on atomic force microscopy cantilevers, in The Cell Surface, 5, 100021-100021.
Nanomotion Detection Method for Testing Antibiotic Resistance and Susceptibility of Slow-Growing Bacteria
Villalba María Ines, Stupar Petar, Chomicki Wojciech, Bertacchi Massimiliano, Dietler Giovanni, Arnal Laura, Vela María Elena, Yantorno Osvaldo, Kasas Sandor (2018), Nanomotion Detection Method for Testing Antibiotic Resistance and Susceptibility of Slow-Growing Bacteria, in Small, 14(4), 1702671-1702671.
DNA-protein interactions explored by atomic force microscopy
Kasas Sandor, Dietler Giovanni (2018), DNA-protein interactions explored by atomic force microscopy, in Seminars in Cell & Developmental Biology, 73, 231-239.

Collaboration

Group / person Country
Types of collaboration
Prof. Alison Murray, University of Nevada, Reno United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
Resistell, Muttenz Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
- Industry/business/other use-inspired collaboration
Prof. Ronnie Willaert, VUB, Bruxelles Belgium (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Dr. G. Putrino, University of Western Australia, Perth Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Industry/business/other use-inspired collaboration
Nanosurf, Liestal Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Industry/business/other use-inspired collaboration
Prof. Maria Starodubtseva, Gomel State Medical University, Gomel Belarus (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Anna Panorska, University of Nevada, Reno United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
21th Annual Linz Winter Workshop Poster Monitoring cellular nanometric scale oscillations by AFM 01.02.2020 Linz, Austria Kasas Sandor;
Physics for the Life Sciences Talk given at a conference Nanomotion based antibiotic sensitivity test 14.10.2019 St. Petersburg, Russia Kasas Sandor;
Physics for the Life Sciences Talk given at a conference Nanomotion based antibiotic sensitivity test 14.10.2019 St Petersburg, Russia Kasas Sandor;
Swiss Physical Society (SPS) Joint Annual Meeting Poster Microfabricated cantilever beams for rapid bacterial sensitivity tests 26.08.2019 Zurich, Switzerland Malovichko Anton;
Scanning Probe Microscopy Talk given at a conference Nanomotion based antibiotic sensitivity test 22.08.2019 Ekaterinburg, Russia Kasas Sandor;
Scanning Probe Microscopy Talk given at a conference Nanomotion based antibiotic sensitivity test 22.08.2019 Ekaterinburg, Russia Kasas Sandor;
16th International Workshop on Nanomechanical Sensors (NMC-2019) Poster Microfabricated polymer cantilevers for rapid bacterial sensitivity tests 19.06.2019 Lausanne, Switzerland Malovichko Anton;
16th International Workshop in Nanomechanical Sensors Poster Identifying resistance with glass fibers 19.06.2019 Lausanne, Switzerland Guérin Kamila Krystyna;
20th CMi Annual Review Meeting Poster SU-8 cantilevers for nanomechanical motion detection 07.05.2019 Lausanne, Switzerland Malovichko Anton;
Brain and Neuroplasticity : Structural and Molecular Aspects Talk given at a conference AFM based nanomotion detection of living organism: medical and astrobiological applications 01.05.2019 Tbilisi, Georgia Kasas Sandor;
Brain and Neuroplasticity : Structural and Molecular Aspects Talk given at a conference AFM based nanomotion detection of living organism: medical and astrobiological applications 01.05.2019 Tbilisi, Georgia Kasas Sandor;
NFP Meeting Poster Microfabricated nanomotion detectors for ultra-rapidbacterial sensitivity tests 27.03.2019 Lausanne, Switzerland Malovichko Anton;
21th Annual Linz Winter Workshop Poster Monitoring cellular nanometric scale oscillations by AFM 03.02.2019 Linz, Austria Kasas Sandor;
Silamed 2018 Talk given at a conference Diagnostique rapide de la résistance aux antibiotiques par le microscope à force atomique 27.11.2018 Suisse, Switzerland Kasas Sandor;
BySPM-2018 Talk given at a conference Nanomotion based detection of living organism: medical and astrobiological applications 17.10.2018 Minsk, Belarus Kasas Sandor;
From Solid State to Biophysics IX Talk given at a conference Applications of nanomotion based living organism detection 16.06.2018 Cavtat, Croatia Kasas Sandor;
XX. Annual Linz Winter Workshop Talk given at a conference AFM based living organisms nanomotion detection 02.02.2018 Linz, Austria Kasas Sandor;
6ième journée de formation en microbiologie diagnostique Talk given at a conference Nano-motion based detection of living microorganisms 03.10.2017 Lausanne, Switzerland Kasas Sandor; Greub Gilbert;
AFM biomed conference 2017 Talk given at a conference Nano-motion based detection of living microorganisms 04.09.2017 Krakow, Poland Kasas Sandor;


Communication with the public

Communication Title Media Place Year
Video/Film Rapid Evaluation of Antibiotic Resistances International 2018

Associated projects

Number Title Start Funding scheme
166252 Monitoring Nanoscale Motion of Biological Organisms 01.04.2016 Project funding (Div. I-III)
173863 Multidisciplinary approaches to identify genetic determinants of Candida albicans pathogenicity 01.10.2017 Sinergia

Abstract

We propose to develop a new rapid phenotypic based diagnostic test to characterize bacterial sensitivity to antibiotics. Beside molecular biology based methods, a phenotypic tool has the advantage not to rely on already known resistances or on the knowledge of the involved bacteria. The proposed technique is very fast compared to the actual available diagnostic tools, and we foresee that our device will give reliable complete antibiograms in a time span of an hour. This aspect is particularly important in the case of slow growing bacteria where the standard characterization technique might take up to 30 days (tuberculosis, bordetella). The proposed device is based on a patented nanomechanical detection of the movements that characterize living organism. The living specimens (bacteria in our case) are attached to a nano-mechanical sensor (optical fibre) and exposed to different antibiotics. The optical fibres sense the nanoscale movements of the bacteria and monitor online the bacterial response to the drugs. Our team has already shown that a wide range of bacteria types can be characterized with the proposed technology. In the present proposal we are aiming at delivering a multisensor device that can be employed in microbiology laboratories to test in parallel different antibiotics at varying concentrations to deliver a complete antibiotic susceptibility profile and that will be of easy manipulation. As a result medical doctors could immediately target an infected patients bacteria with the most appropriate antibiotic and avoid the use of large spectrum antibiotics that may lead to side effects and that are known to induce resistance. The present proposal includes also an important part dedicated to the collaboration with the CHUV Lausanne where the device will be tested in the microbiology laboratory under near hospital conditions. The long-term goal of this project is to build a fully automated device that can be routinely used in laboratories.
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