RECOMBINA at the SEM Molecular Microbiology meetingRECOMBINA at the SEM Molecular Microbiology meeting

RECOMBINA at the SEM Molecular Microbiology meetingRECOMBINA at the SEM Molecular Microbiology meeting

Monday September 5th, 2016

Between the 6th and 8th of September we will attend the XI Meeting of the Specialized Group of Molecular Microbiology of the Spanish Society of Microbiology that will be held at the Hotel Silken Al-Andalus Palace in Sevilla, Spain. Below is the abstract of our poster that will be displayed at the panel 90.

 

A different slant in anti-biofilm drug discovery

Juana María Prieto1, Iñigo Lasa2 and Cristina Latasa1

 

1 Recombina SL. Calle Nueva 8 local 10, 31192 Mutilva, Navarra, España.
2 Navarrabiomed-Universidad Pública de Navarra, IdiSNA, Pamplona-31008, Navarra, Spain

After 100 years of extensive research, it may be said that we are capable of keep acute infections at bay. Though, we are witnessing a rising concern about the dramatic spread of antibiotic-resistant strains and chronic infections caused by biofim-forming bacteria, against whom traditional therapies are not sufficiently effective. Specially worrying are the matrix-enclosed communities assembled by the pathogens Staphyloccocus aureus and epidermidis, the most frequent causes of nosocomial infections and infections on indwelling medical devices. The polysaccharide PIA/PNAG is a major component of staphylococcal biofilms. The production of this high molecular weight polymer depends on the proteins encoded in the icaADBC intercellular adhesion locus, an operon that is subjected to strict regulation, both at transcriptional and post-transcriptional levels. Contrary to what it might seem, production of PIA/PNAG does not always confer a selective advantage, proof of which are the on-off mechanisms like phase-variation that regulate its expression (Arciola, Campoccia, Ravaioli, & Montanaro, 2015). Our work hypothesis is based on the fact that production or overproduction of PIA/PNAG entails a significant fitness cost for the bacteria and such process might be turned toxic, and thus become an Achilles heel. We have designed a High Throughput Screening assay in which several PIA/PNAG overproducer strains and their icaADBC mutant counterparts have been treated with different concentrations of a collection of marine extracts and compounds. Up to date, we have selected two compounds, previously proved to possess antibiotic and antibiotic-cytotoxic activities respectively, and five crude extracts proceeding from the fermentation of marine Actinomyces and fungal species that specifically inhibit, or do it in significant higher levels, the growth of those strains capable of producing a PIA/PNAG-dependent biofilm in comparison to their PIA/PNAG-defective derivatives. Further studies are being undertaken in order to characterize the molecular mechanisms undelaying the action of these compounds/extracts and their potential synergies whether in combination between them or with classical antibiotics.

Arciola, C. R., Campoccia, D., Ravaioli, S., & Montanaro, L. (2015). Polysaccharide intercellular adhesin in biofilm: structural and regulatory aspects. Frontiers in Cellular and Infection Microbiology, 5(114), 7. http://doi.org/10.3389/fcimb.2015.00007

This project is supported by the Spanish Ministry of Economy and Competitiveness (Retos-Colaboración 2015 call)Between the 6th and 8th of September we will attend the XI Meeting of the Specialized Group of Molecular Microbiology of the Spanish Society of Microbiology that will be held at the Hotel Silken Al-Andalus Palace in Sevilla, Spain. Below is the abstract of our poster that will be displayed at the panel 90.

 

A different slant in anti-biofilm drug discovery

Juana María Prieto1, Iñigo Lasa2 and Cristina Latasa1

 
After 100 years of extensive research, it may be said that we are capable of keep acute infections at bay. Though, we are witnessing a rising concern about the dramatic spread of antibiotic-resistant strains and chronic infections caused by biofim-forming bacteria, against whom traditional therapies are not sufficiently effective. Specially worrying are the matrix-enclosed communities assembled by the pathogens Staphyloccocus aureus and epidermidis, the most frequent causes of nosocomial infections and infections on indwelling medical devices. The polysaccharide PIA/PNAG is a major component of staphylococcal biofilms. The production of this high molecular weight polymer depends on the proteins encoded in the icaADBC intercellular adhesion locus, an operon that is subjected to strict regulation, both at transcriptional and post-transcriptional levels. Contrary to what it might seem, production of PIA/PNAG does not always confer a selective advantage, proof of which are the on-off mechanisms like phase-variation that regulate its expression (Arciola, Campoccia, Ravaioli, & Montanaro, 2015). Our work hypothesis is based on the fact that production or overproduction of PIA/PNAG entails a significant fitness cost for the bacteria and such process might be turned toxic, and thus become an Achilles heel. We have designed a High Throughput Screening assay in which several PIA/PNAG overproducer strains and their icaADBC mutant counterparts have been treated with different concentrations of a collection of marine extracts and compounds. Up to date, we have selected two compounds, previously proved to possess antibiotic and antibiotic-cytotoxic activities respectively, and five crude extracts proceeding from the fermentation of marine Actinomyces and fungal species that specifically inhibit, or do it in significant higher levels, the growth of those strains capable of producing a PIA/PNAG-dependent biofilm in comparison to their PIA/PNAG-defective derivatives. Further studies are being undertaken in order to characterize the molecular mechanisms undelaying the action of these compounds/extracts and their potential synergies whether in combination between them or with classical antibiotics.

1 Recombina SL. Calle Nueva 8 local 10, 31192 Mutilva, Navarra, España.
2 Navarrabiomed-Universidad Pública de Navarra, IdiSNA, Pamplona-31008, Navarra, Spain

This project is supported by the Spanish Ministry of Economy and Competitiveness (Retos-Colaboración 2015 call)