Low-molecular-mass penicillin binding protein 6b (DacD) is required for efficient GOB-18 metallo-b-lactamase biogenesis in Salmonella enterica and Escherichia coli

BRAMBILLA L, MORÁN BARRIO J, VIALE AM.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2013

0066-4804

Metallo-b-lactamases (MBLs) are Zn2+containing secretory enzymes of clinical relevance, whose final folding and metal ion assembly steps in Gram-negative bacteria occur after secretion of the apo form to the periplasmic space. In the search of periplasmic factors assisting MBL biogenesis, we found that dacD null (Delta-dacD) mutants of Salmonella enterica and Escherichia coli expressing the pre-GOB-18 MBL gene from plasmids showed significantly reduced resistance to cefotaxime and concomitant lower accumulation of GOB-18 in the periplasm. This reduced accumulation of GOB-18 resulted from increased accessibility to proteolytic attack in the periplasm, suggesting that the lack of DacD negatively affects the stability of secreted apoMBL forms. Moreover, delta-dacD mutants of S. enterica and E. coli showed both an altered ability to develop biofilm growth. DacD is a widely distributed low molecular mass (LMM) penicillin binding protein (PBP6b) endowed with low DD-carboxypeptidase activity and whose functions are still obscure. Our results indicate roles for DacD in assisting biogenesis of particular secretory macromolecules in Gram-negative bacteria, and represent to our knowledge the first reported phenotypes for bacterial mutants lacking this LMM PBP.