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H2020Individual fellowship2018–2020

Vanrestrep · Vancomycin resistance regulation in the antibiotic-producers streptomycetes

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2018-02-01 → 2020-01-31
EU contribution
€158,122
Participants
1
Scheme
MSCA-IF-EF-ST

Lines connect the coordinator with its partners.

Results in brief

Vancomycin resistance regulation in the antibiotic-producers streptomycetes

An active area of research aimed at combatting the growing problem of antimicrobial resistance is to develop compounds that interfere with resistance mechanisms and therefore greatly prolong the use of existing drugs. An example of a condition that attenuates resistance to an antibiotic is found in Streptomyces coelicolor when high levels of phosphate (in the presence of vancomycin) are added in the growth medium. The general objective of this work was to understand the effect of the availability of phosphate (Pi) on the vancomycin resistance (VR) mechanism of the model Gram-positive bacterium S. coelicolor. In particular, this project had two key Research Objectives: a) the study of the nutritional regulation of VR and its link with the cell wall composition, b) the study of the Post-transcriptional regulation of the VR genes with special focus on the role of small RNAs.

Data: CORDIS, © European Union

Project objective

Antimicrobial resistance is a critical health issue today. Important pathogens have become resistant to many or all available antibiotics and limited new antibiotics are in the pipeline. Vancomycin is used as a ‘last resort’ antibiotic treatment for many bacterial infections, but worryingly vancomycin resistance (VR) has spread to major hospital-acquired pathogens such as Enterococcus faecium and Staphylococcus aureus. Most pathogen VR gene clusters likely came from actinomycetes, the natural producers of glycopeptides and most other antibiotics of natural origin. Induction of VR in the model actinomycete Streptomyces coelicolor is highly influenced by nutritional conditions, in particular by the phosphate (Pi) concentration in the medium. My previous work has shown that VR in S. coelicolor is blocked with Pi concentrations above 0.2%; suggesting a key role of this nutrient in VR repression. Furthermore, I have isolated a mutant strain (SCO2594::aac(3)IV) lacking this Pi control over VR. This mutant has cell wall synthesis defects and up-regulates a putative small non-coding RNA (sRNA) located in the promoter region of the vanSR regulatory genes. This project aims to understand the mechanisms of Pi regulation of the S. coelicolor van cluster, and to expand this study to other nutrients that may also control VR. A main focus is on the role of sRNAs in the regulation, as they offer potential novel targets for future clinical exploitation such as “antisense RNA therapy”. The work also aims to understand the role of SCO2594 in VR and to identify new players involved in the process. The proposed project represents an excellent opportunity for the researcher to develop new skills whilst helping to ramp up the development of new antimicrobial platforms in the Salas lab.

Original text from CORDIS.

Participants

  • UNIVERSIDAD DE OVIEDO · OVIEDOCoordinatorSpain

Links

Data: CORDIS, © European Union