Evaluation of UTP-Glucose-1-phosphate uridylyl transferase (UDPG:PP) as a potential novel drug target in Streptococcus pneumoniae.

COOLS F ; VANHOUTTE BIEKE; TORFS E; BIDART DE MACEIDO M; BONOFIGLIO, LAURA; CAPPOEN D,; MOLLERACH, M.; COS P

Valencia

Congreso; 7 th Congress of European Microbiologist; 2017

FEMS

BACKGROUND - The most important virulence factor of the human pathogen Streptococcus pneumoniae is its polysaccharide capsule, which prevents opsonization by complement factors,adhesion and macrophage phagocytosis. Uridine diphosphate glucose (UDP-Glc) is a key component in the biosynthetic pathway of capsular polysaccharides and is also present in other bacteria where it plays a role in lipopolysaccharide and capsule production. It is formed out of glucose 1-phosphate (Glc-1P) by the enzyme UTP-glucose-1-phosphate uridylyltransferase (UDPG:PP), which is encoded by the galU gene. UDPG:PP is widely distributed amongst animals, plants and other microorganisms, but eukaryotic UDPG:PPs are evolutionary unrelated to their prokaryotic counterparts. Therefore, it is postulated that UDPG:PP might be a valuable novel target in fighting bacterial diseases. OBJECTIVES . To assess the potential value of UDPG:PP in antimicrobial therapy, several in vitro characteristics and the in vivo infectivity of different pneumococcal galU knockout strains were compared with those of their non-mutated parent strains. METHODS. In vitro data on biofilm formation, antimicrobial susceptibility and co-cultures with macrophages and epithelial cells were generated using standard methods. Transmission electron microscopy was used to visualize the capsule and in vivo infectivity was determined using a Galleria mellonella model. CONCLUSIONS. Although there is no definitive correlation found for all strains and their knockouts, our results suggest that galU mutations influence in vitro biofilm formation. Furthermore, results of cellular co-cultures combined with the primary results of infectivity imply UDPG:PP might indeed be a potential new target.