Spatial regulation of protein A in Staphylococcus aureus

被引:16
作者
Zhang, Ran [1 ]
Shebes, Mac A. [1 ]
Kho, Kelvin [2 ]
Scaffidi, Salvatore J. [1 ]
Meredith, Timothy C. [2 ]
Yu, Wenqi [1 ]
机构
[1] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol CMMB, 4202 E Fowler Ave,ISA2015, Tampa, FL 33620 USA
[2] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA
关键词
lipoteichoic acid (LTA); LTA D-alanylation; LysM domain; protein A; Staphylococcus aureus; YSIRK; GXXS signal peptide; LIPOTEICHOIC ACID SYNTHESIS; CELL-WALL; SURFACE-PROTEINS; TEICHOIC-ACIDS; LISTERIA-MONOCYTOGENES; STREPTOCOCCUS-PYOGENES; DLT OPERON; SORTASE; BINDING; MECHANISM;
D O I
10.1111/mmi.14734
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Surface proteins of Staphylococcus aureus play vital roles in bacterial physiology and pathogenesis. Recent work suggests that surface proteins are spatially regulated by a YSIRK/GXXS signal peptide that promotes cross-wall targeting at the mid-cell, though the mechanisms remain unclear. We previously showed that protein A (SpA), a YSIRK/GXXS protein and key staphylococcal virulence factor, mis-localizes in a ltaS mutant deficient in lipoteichoic acid (LTA) production. Here, we identified that SpA contains another cross-wall targeting signal, the LysM domain, which, in addition to the YSIRK/GXXS signal peptide, significantly enhances SpA cross-wall targeting. We show that LTA synthesis, but not LtaS, is required for SpA septal anchoring and cross-wall deposition. Interestingly, LTA is predominantly found at the peripheral cell membrane and is diminished at the septum of dividing staphylococcal cells, suggesting a restriction mechanism for SpA septal localization. Finally, we show that D-alanylation of LTA abolishes SpA cross-wall deposition by disrupting SpA distribution in the peptidoglycan layer without altering SpA septal anchoring. Our study reveals that multiple factors contribute to the spatial regulation and cross-wall targeting of SpA via different mechanisms, which coordinately ensures efficient incorporation of surface proteins into the growing peptidoglycan during the cell cycle.
引用
收藏
页码:589 / 605
页数:17
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