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Specialized peptidoglycan hydrolases sculpt the intra-bacterial niche of predatory Bdellovibrio and increase population fitness

DOI: 10.1371/journal.ppat.1002524 DOI Help
PMID: 22346754 PMID Help

Authors: Andy Lovering (University of Birmingham, U.K.) , T. R. Lerner (School of Biology, University of Nottingham, U.K.) , Nhat Khai Bui (The Centre for Bacterial Cell Biology, Newcastle University, U.K.) , K. Uchida (Prefectural University of Hiroshima, Japan) , Shin-Ichi Aizawa (Prefectural University of Hiroshima, Japan) , Waldemar Vollmer (The Centre for Bacterial Cell Biology, Newcastle University,) , Elizabeth Sockett (University of Nottingham, Medical School, Nottingham, U.K.)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos Pathogens , VOL 8 (2)

State: Published (Approved)
Published: February 2012
Diamond Proposal Number(s): 6388

Open Access Open Access

Abstract: Bdellovibrio are predatory bacteria that have evolved to invade virtually all Gram-negative bacteria, including many prominent pathogens. Upon invasion, prey bacteria become rounded up into an osmotically stable niche for the Bdellovibrio, preventing further superinfection and allowing Bdellovibrio to replicate inside without competition, killing the prey bacterium and degrading its contents. Historically, prey rounding was hypothesized to be associated with peptidoglycan (PG) metabolism; we found two Bdellovibrio genes, bd0816 and bd3459, expressed at prey entry and encoding proteins with limited homologies to conventional dacB/PBP4 DD-endo/carboxypeptidases (responsible for peptidoglycan maintenance during growth and division). We tested possible links between Bd0816/3459 activity and predation. Bd3459, but not an active site serine mutant protein, bound ?-lactam, exhibited DD-endo/carboxypeptidase activity against purified peptidoglycan and, importantly, rounded up E. coli cells upon periplasmic expression. A ?Bd0816 ?Bd3459 double mutant invaded prey more slowly than the wild type (with negligible prey cell rounding) and double invasions of single prey by more than one Bdellovibrio became more frequent. We solved the crystal structure of Bd3459 to 1.45 Å and this revealed predation-associated domain differences to conventional PBP4 housekeeping enzymes (loss of the regulatory domain III, alteration of domain II and a more exposed active site). The Bd3459 active site (and by similarity the Bd0816 active site) can thus accommodate and remodel the various bacterial PGs that Bdellovibrio may encounter across its diverse prey range, compared to the more closed active site that “regular” PBP4s have for self cell wall maintenance. Therefore, during evolution, Bdellovibrio peptidoglycan endopeptidases have adapted into secreted predation-specific proteins, preventing wasteful double invasion, and allowing activity upon the diverse prey peptidoglycan structures to sculpt the prey cell into a stable intracellular niche for replication.

Journal Keywords: Bdellovibrio; Prey Rounding; Predation-Specific Proteins

Subject Areas: Medicine

Instruments: I03-Macromolecular Crystallography