Structural Basis of the Novel S. pneumoniae Virulence Factor, GHIP, a Glycosyl Hydrolase 25 Participating in Host-Cell Invasion

Niu, Siqiang; Luo, Miao; Zhou, Hua; Zhang, Yanli; Min, Xun; Cai, Xue-Fei; Zhang, Wenlu; Xu, Wenchu; Li, Defeng; Ding, Jingjin; Hu, Yuming; Wang, Dacheng; Huang, Aiping; Yin, Yibin; Wang, Deqiang

doi:10.1371/journal.pone.0068647

Cited by 12 publications

(13 citation statements)

References 52 publications

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“… Abbreviations: ABC, ATP-binding cassette; DHAP, dihydroxyacetone phosphate; IgG, immunoglobulin G; IL, interleukin; Th, T helper; TNF, tumor necrosis factor. *Structurally this family is part of the six hairpin glycosidase superfamily, suggesting a glycosyl hydrolase, which is one of the virulence gene ( Niu et al , 2013 ). …”

Section: Figurementioning

confidence: 99%

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Comparative genome analysis and identification of competitive and cooperative interactions in a polymicrobial disease

et al. 2014

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Polymicrobial diseases are caused by combinations of multiple bacteria, which can lead to not only mild but also life-threatening illnesses. Periodontitis represents a polymicrobial disease; Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, called ‘the red complex', have been recognized as the causative agents of periodontitis. Although molecular interactions among the three species could be responsible for progression of periodontitis, the relevant genetic mechanisms are unknown. In this study, we uncovered novel interactions in comparative genome analysis among the red complex species. Clustered regularly interspaced short palindromic repeats (CRISPRs) of T. forsythia might attack the restriction modification system of P. gingivalis, and possibly work as a defense system against DNA invasion from P. gingivalis. On the other hand, gene deficiencies were mutually compensated in metabolic pathways when the genes of all the three species were taken into account, suggesting that there are cooperative relationships among the three species. This notion was supported by the observation that each of the three species had its own virulence factors, which might facilitate persistence and manifestations of virulence of the three species. Here, we propose new mechanisms of bacterial symbiosis in periodontitis; these mechanisms consist of competitive and cooperative interactions. Our results might shed light on the pathogenesis of periodontitis and of other polymicrobial diseases.

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Section: Figurementioning

confidence: 99%

“… *Structurally this family is part of the six hairpin glycosidase superfamily, suggesting a glycosyl hydrolase, which is one of the virulence gene ( Niu et al , 2013 ). …”

Section: Figurementioning

confidence: 99%

Comparative genome analysis and identification of competitive and cooperative interactions in a polymicrobial disease

et al. 2014

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“…B. Multiple sequence alignment of catalytic domains from various members of the GH25 family, including EADP40, the Bacillus phage endolysin PlyB (Porter et al ., ) (PDB: 2NW0), the Streptococcus pneumoniae virulence factor GHIP (Niu et al ., ) (WP_001231235), the S. pneumonia autolysin LytC (Garcia et al ., ) (PDB: 2WW5), the S. pneumoniae phage endolysin Cpl‐1 (Hermoso et al ., ) (accession number NP_044837), the S. pneumoniae phage endolysin Cpl‐7 (Silva‐Martin et al ., ) (P19385.2) and Streptomyces coelicolor bacterial muramidase Cellosyl (Rau et al ., ) (PDB: 1JFX). Conserved residues are highlighted in red.…”

Section: Resultsmentioning

confidence: 99%

Structural insights into the binding and catalytic mechanisms of the Listeria monocytogenes bacteriophage glycosyl hydrolase PlyP40

Romero

Bartual

Schmelcher

et al. 2018

Molecular Microbiology

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Endolysins are bacteriophage-encoded peptidoglycan hydrolases that specifically degrade the bacterial cell wall at the end of the phage lytic cycle. They feature a distinct modular architecture, consisting of enzymatically active domains (EADs) and cell wall-binding domains (CBDs). Structural analysis of the complete enzymes or individual domains is required for better understanding the mechanisms of peptidoglycan degradation and provides guidelines for the rational design of chimeric enzymes. We here report the crystal structure of the EAD of PlyP40, a member of the GH-25 family of glycosyl hydrolases, and the first muramidase reported for Listeria phages. Site-directed mutagenesis confirmed key amino acids (Glu98 and Trp10) involved in catalysis and substrate stabilization. In addition, we found that PlyP40 contains two heterogeneous CBD modules with homology to SH3 and LysM domains. Truncation analysis revealed that both domains are required for full activity but contribute to cell wall recognition and lysis differently. Replacement of CBDP40 with a corresponding domain from a different Listeria phage endolysin yielded an enzyme with a significant shift in pH optimum. Finally, domain swapping between PlyP40 and the streptococcal endolysin Cpl-1 produced an intergeneric chimera with activity against Listeria cells, indicating that structural similarity of individual domains determines enzyme function.

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“…Successful transformation was selected by plating on blood agar plates containing chloramphenicol. S. pneumoniae strains were grown in C+Y (casamino acid & yeast extract) medium , and cells in the exponential phase were used for experiments. Purified GHIP was obtained as reported in our former publication .…”

Section: Methodsmentioning

confidence: 99%

GHIP in Streptococcus pneumoniae is involved in antibacterial resistance and elicits a strong innate immune response through TLR2 and JNK/p38MAPK

Dong

Wang

et al. 2014

The FEBS Journal

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Interaction between pneumococcal virulence factors and innate immune receptors triggers host responses via specific signaling pathways after infection. By generating a deficient mutant, we show here that, compared with the wild‐type parent strain, glycosyl hydrolase 25 relating to invasion protein (GHIP) mutant strain was impaired in rapid dissemination into vessels and caused less severe inflammation in mice lungs. Further study demonstrated that the lack of this protein in Streptococcus pneumoniae caused an increased susceptibility to whole blood or neutrophils, while this impairment could be recovered by supplementing recombinant GHIP (rGHIP). Additionally, secreted GHIP could be detected in culture medium, and purified protein was able to induce the release of tumor necrosis factor α and interleukin 6 from peritoneal macrophages. Further investigations revealed that the induction of interleukin 6 by this virulence factor depended on the phosphorylation of c‐Jun N‐terminal kinase and p38 mitogen activated protein kinase and Toll‐like receptor 2. Taken together, GHIP, a novel pneumococcal virulence factor, appeared to play a critical role in bacterial survival and the induction of host innate immune response during pneumococcal infection.

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Structural Basis of the Novel S. pneumoniae Virulence Factor, GHIP, a Glycosyl Hydrolase 25 Participating in Host-Cell Invasion

Cited by 12 publications

References 52 publications

Comparative genome analysis and identification of competitive and cooperative interactions in a polymicrobial disease

Comparative genome analysis and identification of competitive and cooperative interactions in a polymicrobial disease

Structural insights into the binding and catalytic mechanisms of the Listeria monocytogenes bacteriophage glycosyl hydrolase PlyP40

GHIP in Streptococcus pneumoniae is involved in antibacterial resistance and elicits a strong innate immune response through TLR2 and JNK/p38MAPK

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