Premium
Suppression of a deletion mutation in the gene encoding essential PBP2b reveals a new lytic transglycosylase involved in peripheral peptidoglycan synthesis in S treptococcus pneumoniae D39
Author(s) -
Tsui HoChing Tiffany,
Zheng Jiaqi J.,
Magallon Ariel N.,
Ryan John D.,
Yunck Rachel,
Rued Britta E.,
Bernhardt Thomas G.,
Winkler Malcolm E.
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13366
Subject(s) - peptidoglycan , biology , mutant , lytic cycle , lysin , regulon , streptococcus pneumoniae , penicillin binding proteins , gene , cell wall , mutation , genetics , escherichia coli , microbiology and biotechnology , bacteria , bacteriophage , virus
Summary In ellipsoid‐shaped ovococcus bacteria, such as the pathogen Streptococcus pneumoniae (pneumococcus), side‐wall (peripheral) peptidoglycan (PG) synthesis emanates from midcells and is catalyzed by the essential class B penicillin‐binding protein PBP2b transpeptidase (TP). We report that mutations that inactivate the pneumococcal YceG‐domain protein, Spd_1346 (renamed MltG), remove the requirement for PBP2b. Δ mltG mutants in unencapsulated strains accumulate inactivation mutations of class A PBP1a, which possesses TP and transglycosylase (TG) activities. The ‘synthetic viable’ genetic relationship between Δ pbp1a and Δ mltG mutations extends to essential Δ mreCD and Δ rodZ mutations that misregulate peripheral PG synthesis. Remarkably, the single MltG(Y488D) change suppresses the requirement for PBP2b, MreCD, RodZ and RodA. Structural modeling and comparisons, catalytic‐site changes and an interspecies chimera indicate that pneumococcal MltG is the functional homologue of the recently reported MltG endo‐lytic transglycosylase of Escherichia coli . Depletion of pneumococcal MltG or mltG (Y488D) increases sphericity of cells, and MltG localizes with peripheral PG synthesis proteins during division. Finally, growth of Δ pbp1a Δ mltG or mltG (Y488D) mutants depends on induction of expression of the WalRK TCS regulon of PG hydrolases. These results fit a model in which MltG releases anchored PG glycan strands synthesized by PBP1a for crosslinking by a PBP2b:RodA complex in peripheral PG synthesis.