SENBIOTAR: Sensiting Pseudomonas aeruginosa biofilms to antibiotics and reducing virulence through novel target inhibition

Lead Research Organisation: University of Nottingham
Department Name: School of Life Sciences

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

The traditional approach to combating bacterial infections has been based on the use of antibiotics
which kill bacteria or inhibit their growth. There has also been a strong emphasis on the
identification of essential gene targets for drug intervention. A major problem with therapeutic
approaches targeting viability is that they induce strong selective pressures resulting in the rapid
emergence of antimicrobial resistance. An alternate approach is to inhibit virulence rather than
bacterial viability and this will be explored in the SENBIOTAR project. In the opportunistic human
pathogen Pseudomonas aeruginosa, virulence is co-ordinately controlled at the bacterial population
level through quorum sensing (QS), a global cell-to-cell communication system employing diffusible
signal molecules. P. aeruginosa strains with mutations in the Pseudomonas Quinolone Signal (PQS)
QS pathway are avirulent in experimental animal infections. The partners of this consortium will
exploit this information by optimising hit compounds and peptide nucleic acids (PNAs) they
identified previously which target PQS biosynthesis and/or PQS signal transduction. These hits have
been shown to not only render P. aeruginosa avirulent but also to sensitize biofilms to the action of
antibiotics. One of the limitations of using inhibitors of virulence is the fact that
immunocompromised patients may not be able to clear the targeted pathogen efficiently. However,
if the pathogen can, at the same time, be sensitised to antibiotics then there is great scope for dual
therapy with PQS inhibitors and antibiotics. SENBIOTAR will bring together world experts in QS,
medicinal chemistry, PNAs, drug delivery and preclinical studies to optimise the activity of the hit
compounds and PNAs (hit-to-lead optimization) with the intention of identifying lead compounds
which strongly inhibit QS, attenuate virulence and sensitise biofilms to conventional antibiotics at
sub-micromolar concentrations. This will be achieved by improving (a) their physicochemical
properties without the emergence of cytotoxicity, and (b) delivery to the site of infection. These
studies will be performed using a combination of in vitro virulence and biofilm bioassays alongside
experimental animal lung infection models. The lead compounds developed by SENBIOTAR will also
have significant potential for the treatment of wound, bloodstream and medical-device associated
infections caused by P. aeruginosa.
 
Description Conference participation (Central European Symposium on Antimicrobials and Antimicrobial Resistant (CESAR)) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Presentation of the data from SENBIOTAR at an antimicrobials conference in Croatia. There were around 120 participants form a wide range of academic and research institutions in Europe. There was a significant level of discussion amounts all participants around the data presented and this has resulted in the triggering of some discussions for future collaborative work.
Year(s) Of Engagement Activity 2018
URL http://hmd-cms.hr/cesar2018/
 
Description Early Discovery of New Antibiotics Workshop (Paris) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Third sector organisations
Results and Impact The purpose of this workshop was to share ideas on antibiotic development between upstream and developers by bringing the PIs in project areas of antibiotic early discovery and those in clinical development in order to identify potential candidates and increase awareness of entry requirements. It also promote increased awareness at early stage of entry requirements about future clinical developments and showcased early work on screening and identification of new targets. The title of the presentation given by Miguel Camara was: SENBIOTAR: Sensitising Pseudomonas aeruginosa biofilms to antibiotics and reducing virulence through novel target inhibition.
Year(s) Of Engagement Activity 2017
 
Description FIP Pharmaceutical Sciences World Congress, Stockholm (Oral presentation) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Conference talk:- Sou T, Kukavica-Ibrulj I, Soukarieh F, Halliday N, Levesque RC, Williams P, et al. Quorum sensing inhibitors for pulmonary delivery as a novel treatment strategy against Pseudomonas aeruginosa. FIP Pharmaceutical Sciences World Congress, Stockholm, Sweden. 21st - 24th May 2017. The purpose was to promote the activities fo SENBIOTAR.
Year(s) Of Engagement Activity 2017
URL http://pswc2017.fip.org/
 
Description First Uganda National Conference on Antimicrobial Resistance 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Poster presentation of an MSc student who presented the research he carried out at Nottingham as part of the SENBIOTAR program. He represented to researchers in Uganda some of the highlights of this research program. The title of his poster was: Characterisation of inhibitors of the PqsR quorum sensing regulator in Pseudomonas aeruginosa.
Year(s) Of Engagement Activity 2016
 
Description INTERNATIONAL SIMPOSIUM ON " GENE REGULATION IN BACTERIA WITH MEDICAL AND INDUSTRIAL INTEREST' Invited international speaker 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact The title of the invited talk was: 'Exploiting the therapeutic potential of targeting quorum sensing in Pseudomonas aeruginosa'. The symposium was organised by the Universidad Nacional Autonoma de Mexico in Mexico City. It was attended by master students, PhD students and research group leaders.
Year(s) Of Engagement Activity 2018
 
Description International Seminar at the Universidad National Autonoma Mexico 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact This was a seminar to promote the results from the SENBIOTAR programme and identify new collaborations from the results of these programme as well as promote NBIC.
The title of the seminar was: Versatility and targeting of quorum sensing signalling mechanisms
There was a mixed audience of scientists
Year(s) Of Engagement Activity 2018
 
Description Invited talk at symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Sou T, Kukavica-Ibrulj I, Soukarieh F, Halliday N, Levesque RC, Williams P, et al. Quorum sensing inhibitors for pulmonary delivery as a novel treatment against Pseudomonas aeruginosa. FIP Young Scientist Satellite Conference, Uppsala, Sweden. 19th - 21st May 2017. It help disseminating the work from SENBIOTAR amongst your researchers.
Year(s) Of Engagement Activity 2017
URL https://www.scilifelab.se/events/8th-pharmaceutical-profiling-symposium/
 
Description Invited talk- London Microbiome Meeting 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Hosted by the Department of Twin Research at King's College London and held twice a year, the London Microbiome Meeting aim to create a forum to share research that explores the field of microbiomics, providing a broad overview to both research and methodology. It aims to develop a microbiome research network between the various research groups and institutions across London and surrounding area undertaking this work. The title of the presentation was 'Targeting quorum sensing signalling as an antimicrobial strategy' and it has resulted in further engagement activities with a company that attended the meeting.
Year(s) Of Engagement Activity 2018
URL http://londonmicrobiome.org/program.html
 
Description Oral presentation at the 5th UK Cystic Fibrosis Microbiology Consortium Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The activity was an oral presentation entitled: 'Targeting Pseudomonas aeruginosa virulence using novel inhibitors of the alkyl quinolone quorum sensing signalling pathway'. The idea was to inform academics, clinicians, postgraduates students and industry of the current work being carried out in the SENBIOTAR programme as an alternative approach to target Pseudomonas aeruginosa infections in the CF lung.
Year(s) Of Engagement Activity 2016
 
Description Outreach talk at Singapore NTU University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact This workshop was organised by SCELCE in conjunction with the NTU and NUS Universities from Singapore to talk about biofilm research. The talk was joint and Miguel Camara spoke about the work achieved by SENBIOTAR.
Year(s) Of Engagement Activity 2018
 
Description Poster Presentation at the M4 Midland Molecular Microbiology Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Symposium organise as a network activity for microbiology researchers in the Midlands including the Universities of Nottingham, Birmingham, Leicester and Warwick but there were also attendees from other Universities across the country.
Year(s) Of Engagement Activity 2016
 
Description Poster at Pseudomonas 2017 international conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact SENBIOTAR: Sensiting Pseudomonas aeruginosa biofilms to antibiotics and reducing virulence through novel target inhibition
Fadi Soukarieh, Tomas Sou, Mirko Iubatti, Eduard Vico, Irena Kukavica-Ibrulj, Nigel Halliday, Christel AS Bergström, Michael Stocks, Peter Nielsen, Paul Williams, Roger C. Levesque, Miguel Cámara - This poster introduced the main highlights of the SENBIOTAR programme.
Year(s) Of Engagement Activity 2017
URL https://microbiologysociety.org/event/society-events-and-meetings/focused-meeting-2017-16th-internat...
 
Description Poster presentation at international conference in Denmark 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact - Sou T, Kukavica-Ibrulj I, Soukarieh F, Halliday N, Levesque RC, Williams P, et al. Quorum sensing inhibitors for pulmonary delivery as a novel treatment against Pseudomonas aeruginosa. Northern Pharma Network Meeting, Odense, Denmark. 29th - 31st Jan 2018. (Best poster award)
Year(s) Of Engagement Activity 2018
URL http://easp.ee/northern-pharma-network-meeting-2018-odense-denmark/
 
Description Poster presentation at international conference in Liverpool 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Title: Pseudomonas aeruginosa PQS antagonist decreases virulence and increases biofilm sensitivity.
Authors: Vico Oton E., Soukarieh F., Stocks M., Williams P., Heeb S., Cámara M. September 2017,
Focused Meeting 2017: 16th International Conference on Pseudomonas.
Year(s) Of Engagement Activity 2017
URL https://microbiologysociety.org/event/society-events-and-meetings/focused-meeting-2017-16th-internat...
 
Description Poster presentation at international conference in San Diego 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact - Sou T, Kukavica-Ibrulj I, Soukarieh F, Halliday N, Levesque RC, Williams P, et al. A pharmacokinetic model of a new antimicrobial agent after pulmonary delivery for the treatment of chronic Pseudomonas aeruginosa lung infection. American Association of Pharmaceutical Scientists Annual Meeting, San Diego, USA. 12th - 15th Nov 2017. Presentation of results from the SENBIOTAR programme to an international audience
Year(s) Of Engagement Activity 2017
URL https://www.emedevents.com/c/medical-conferences-2017/american-association-of-pharmaceutical-scienti...
 
Description Postgraduate Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact This was a training retreat for postgraduate students and the SENBIOTAR programme was introduced to them as part of a session entitled : 'Targeting virulence as an alternative approach to treat bacterial infections'. This was followed by a discussion with the students.
Year(s) Of Engagement Activity 2016
 
Description Presentation at a national cystic fibrosis consortium meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Title: Sensitising Pseudomonas aeruginosa biofilms to antibiotics
and reducing virulence through novel target inhibition.
Authors: Fadi Soukarieh, Eduard Vico Oton, Jean Dubern, Nigel Halliday, Stephan Heeb, Michael Stocks, Paul
Williams, and Miguel Cámara.
27/ November/ 2017
Cystic Fibrosis Liverpool
Year(s) Of Engagement Activity 2017
 
Description Presentation at international sysmposium on Molecular Medicine 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact "Antisense PNA antibiotics against multiresistant gram negative bacteria", Peter Nielsen, Fredrik Björling , Henrik Franzyk, 21st International Symposium on Molecular Medicine, Athens, Greece, October 2017 Presentation given by Peter Nielsen on behalf of the SENBIOTAR consortium to promote the work done under this consortium
Year(s) Of Engagement Activity 2017
URL https://www.spandidos-publications.com/pages/conference
 
Description Seminar and Shanghai Jiao Tong University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited talk at Shanghai Jiao Tong University. TITLE: Targeting virulence in Pseudomonas aeruginosa as an alternative antibacterial strategy. Presenter: Miguel Camara. This meeting was used to present the results to SENBIOTAR to a broad Chinese audience with a view to explore future collaborations in the area of quorum sensing inhibition
Year(s) Of Engagement Activity 2017
 
Description Seminar at National University of Colombia in Medellin 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited Seminar Universidad Nacional de Colombia in Medellin. Title: Versatilidad de los sistemas de señalización por quorum sensing en bacterias y sus aplicaciones. Presenter Miguel Camara. A collaborative research plan was developed upon this interaction.
Year(s) Of Engagement Activity 2016
 
Description Talk at Central European Symposium on Antimicrobials and Antimicrobial Resistant 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Central European Symposium on Antimicrobials and Antimicrobial Resistant (CESAR),
Šibenik, Croatia 2015-Invited talk Miguel Camara
TITLE: Turning down quorum sensing in Pseudomonas aeruginosa as an antimicrobial strategy
Year(s) Of Engagement Activity 2015
URL http://hmd-cms.hr/cesar2015/
 
Description Talk at International Antimicrobial Resistance conference in Copenhagen 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact ICOHAR International Conference on One Health Antimicrobial Resistance, Copenhagen 2015- Invited Talk Miguel Camara
TITLE: Targeting bacterial inter-cellular signalling as a therapeutic approach
Year(s) Of Engagement Activity 2015
URL https://www.fp7-risksur.eu/news-events/icohar-2015-international-conference-one-health-antimicrobial...
 
Description Talk at Pseudomonas 2017 International Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact 16th International conference on Pseudomonas Liverpool 2017
TITLE: Dissecting and exploiting the pqs quorum sensing system in Pseudomonas aeruginosa
Presenter: Miguel Camara
Year(s) Of Engagement Activity 2017
URL https://microbiologysociety.org/event/society-events-and-meetings/focused-meeting-2017-16th-internat...
 
Description Talk at conference on Peptides in Germany 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact "Peptides for Cellular and in vivo Delivery of PNA Antisense Agents", Peter Nielsen, XII German Peptide Symposium, Darmstadt, Germany, March, 2015. Some of the work on antimicrobial peptides from SENBIOTAR was presented at this conference
Year(s) Of Engagement Activity 2015
URL http://www.eurpepsoc.com/small-symposia/
 
Description University of Tubingen International Summer School 'Microbes, Host and Infection, Bad Urach, Germany July 2018. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Delivered a talk entitled 'Alkylquinolones and Pseudomonas aeruginosa: a tale of regulatory networks, multi- functional signals and antibacterial targets' to both academics and Graduate students which resulted in extended discussions after the event increasing the interest of the graduates into this subject area.
Year(s) Of Engagement Activity 2018