PBP2b participates in the control of shape determination and cell division mechanisms in Streptococcus pneumoniae

ALBARRACÍN ORIO AG; PIÑAS GE; CORTES P; CIAN M,; ECHENIQUE, JOSE

Potrero de Funes, San Luis

Congreso; SAIB; 2011

SAIB

Mutations in penicillin-binding proteins (PBPs) PBP1a, PBP2x, and PBP2b confer β-Lactam resistance in S. pneumoniae. These enzymes are involved in cell wall synthesis and cell division. We described that laboratory strain harboring pbp2b mutations showed morphological abnormalities (rod-shaped cells) with an abnormal septum pattern, suggesting alterations in the cell division mechanism. These cell alterations were restored by the acquisition of pbp2x and pbp1a resistance-conferring mutations obtained from clinical strains, showing evidences of a compensatory evolution mechanism. Analyzing PBP-tag protein fusions, we demonstrated that all these pbp mutations conferred an increased stability to their respective mutant proteins, suggesting that a higher half-life of PBP2x and PBP1a mutant proteins is necessary to compensate the increased half-life of the PBP2b mutant protein (PBP2b*). Probably this compensation is related to a coordinated enzymatic activity between PBPs. In the pbp2b mutants, we demonstrated that the FtsZ and PBP2B* were delocalized, and that PBP2b* displayed a helix manner, similar to that showed by FtsZ in the same pbp2b mutants. By two-hybrid system assays, we detected a protein-protein interaction between FtsZ and PBP2b*, suggesting that the cell division alterations are caused by this interaction. We propose that PBP2b participates in the control of shape determination and cell division mechanisms in S. pneumoniae.