Chromosomal Duplications of MurZ (MurA2) or MurA (MurA1), Amino Acid Substitutions in MurZ (MurA2), and Absence of KhpAB Obviate the Requirement for Protein Phosphorylation in Streptococcus pneumoniae D39
Chromosomal Duplications of MurZ (MurA2) or MurA (MurA1), Amino Acid Substitutions in MurZ (MurA2), and Absence of KhpAB Obviate the Requirement for Protein Phosphorylation in Streptococcus pneumoniae D39
ABSTRACT GpsB links peptidoglycan synthases to other proteins that determine the shape of the respiratory pathogen Streptococcus pneumoniae (pneumococcus; Spn) and other low-GC Gram-positive bacteria. GpsB is also required for phosphorylation of proteins by the essential StkP(Spn) Ser/Thr protein kinase. Here we report three classes of frequently arising chromosomal duplications (≈21-176 genes) containing murZ (MurZ-family homolog of MurA) or murA that suppress ΔgpsB or ΔstkP. These duplications arose from three different repeated sequences and demonstrate the facility of pneumococcus to modulate gene dosage of numerous genes. Overproduction of MurZ or MurA alone or overexpression of MurZ caused by ΔkhpAB mutations suppressed ΔgpsB or ΔstkP phenotypes to varying extents. ΔgpsB and ΔstkP were also suppressed by MurZ amino-acid changes distant from the active site, including one in commonly studied laboratory strains, and by truncation or deletion of the homolog of IreB(ReoM). Unlike in other Gram-positive bacteria, MurZ is predominant to MurA in pneumococcal cells. However, ΔgpsB and ΔstkP were not suppressed by ΔclpCP, which did not alter MurZ or MurA amounts. These results support a model in which regulation of MurZ and MurA activity, likely by IreB(Spn), is the only essential requirement for protein phosphorylation in exponentially growing D39 pneumococcal cells.
Winkler Malcolm E.、Branny Pavel、Doubravov¨￠ Linda、Perez Amilcar J.、Manzoor Irfan、Rued Britta E.、Richardson John D.、Joseph Merrin、Tsui Ho-Ching Tiffany、Zheng Jiaqi J.、Massidda Orietta
Department of Biology, Indiana University BloomingtonInstitute of Microbiology, Czech Academy of SciencesInstitute of Microbiology, Czech Academy of SciencesDepartment of Biology, Indiana University BloomingtonDepartment of Biology, Indiana University BloomingtonDepartment of Biology, Indiana University BloomingtonDepartment of Biology, Indiana University BloomingtonDepartment of Biology, Indiana University BloomingtonDepartment of Biology, Indiana University BloomingtonDepartment of Biology, Indiana University BloomingtonDepartment of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento
分子生物学遗传学微生物学
peptidoglycan precursor synthesisgene duplication and amplificationGpsB peptidoglycan regulatorStkP protein kinaseKhpA/B RNA binding protein
Winkler Malcolm E.,Branny Pavel,Doubravov¨￠ Linda,Perez Amilcar J.,Manzoor Irfan,Rued Britta E.,Richardson John D.,Joseph Merrin,Tsui Ho-Ching Tiffany,Zheng Jiaqi J.,Massidda Orietta.Chromosomal Duplications of MurZ (MurA2) or MurA (MurA1), Amino Acid Substitutions in MurZ (MurA2), and Absence of KhpAB Obviate the Requirement for Protein Phosphorylation in Streptococcus pneumoniae D39[EB/OL].(2025-03-28)[2025-05-15].https://www.biorxiv.org/content/10.1101/2023.03.26.534294.点此复制
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