Thesis projet

Doctoral School ED222

Research Team: Laboratoire d’Innovation Thérapeutique UMR 7200 CNRS – Université de Strasbourg.

Address: 74 Rte du Rhin, 67400 Illkirch-Graffenstaden, France.

PhD Director: Dr Catherine VONTHRON SENECHEAU.

Junior advisor: Dr Sergio ORTIZ.

Title: Pharmacophoric deconvolution analyses of anti-infectious medicinal plants

Although antibiotic resistance has become a major global public health issue in recent years, there are still
few ways to design new anti-infective strategies. Among them, the inhibition of bacterial virulence factors
by natural molecules represents an innovative way to fight bacterial pathogens. Research on medicinal
plants is oriented towards the analysis of traditional practices, both to better understand their
antibacterial/ antivirulence modes of action and to identify natural molecules as drug candidates. We are
particularly interested in traditional European medicine as a local source of new natural
antibacterial/antiviral entities.

A selection of European medicinal plants has been drawn from written or oral sources described for use in
the treatment of various bacterial conditions (skin wounds, respiratory and urinary tract infections). The
objectives of this thesis are: i) to evaluate the ability to disrupt virulence factors of bacterial pathogens by
these medicinal plants, ii) to identify the molecular entities responsible for the antibacterial activity thus
highlighted, iii) identify natural pharmacophores targeting the production of virulence factors and iv)
explore their mechanism of action.

A consortium of researchers was previously set up to tackle this project, involving pharmacognosts,
chemists, microbiologists and immunologists. As part of this consortium, a bank of more than 20 medicinal
plants will be analysed. Methods of chemical analysis and biological properties against bacterial virulence
factor (toxin production, metalloprotein secretion, bacterial communication, quorum sensing, biofilm
formation) were also developed (1, 2). A preliminary screening of the extracts against a panel of pathogenic
bacteria (reference, clinical isolates and multidrug-resistant) will be carried out. These analyses will be
supplemented by methods of differential analysis by NMR, HRMS and molecular networks to identify
biologically active plant compounds in these extracts (3, 4). Antivirulence activity in vivo and synergy with
commercial antibiotics will also be studied (collaboration Sylvie Chevalier, EA4312 University of Rouen
Normandy) of different extracts or isolated active principles (2).

The study of different selected medicinal plants may lead to the identification of molecules of
pharmacological interest and/ or the discovery of antivirulence drug candidates for the treatment of

1. Tahrioui et al., 2020 Front. Microbiol. 11:1068 ; 2. Azuama et al, 2020, Plants 10(12), 1626 ; 3. Margueritte et al., 2018
Magnetic Resonance in Chemistry 56:469-479 ; 4. Kaliq et al., 2022 Molecules 27(3) 963-980.
infections due to pathogenic bacteria. The identification and selection of molecules of interest will open
perspectives of investigation of the mechanisms of action involved.

Wished skills: We are looking for a motivated candidate (to present to the Doctoral School Audition ED222)
with excellent organizational, analytical and autonomous skills and ready to invest in a project at the
interface chemistry-biology both in chemistry of natural substances (extraction, isolation, structural
determination, dereplication), and in in vitro infectiology (antibacterial and cytotoxic tests) fields. It is
strongly desired that the person recruited has a good level in scientific English. Basic programming skills in
python are also desirable.

Expertises which will be acquired during the training: Expertise in pharmacognosy and chemistry of
natural products, solid/liquid extraction and purification techniques by RP-HPLC, mass spectrometry
analysis and dereplication techniques, pharmacophoric analysis and deconvolution techniques by NMR 1D
and 2D, bacterial culture and in vitro antibacterial screening techniques. Project management at the
interface of chemistry and biology and teamwork in a multidisciplinary context.

Application deadline: April 24th, 2024.

Documents to be attached to the application: CV, M2 grades and cover letter

Contacts : ortizaguirre@unistra.fr, vonthron@unistra.fr