M1T1 group A streptococcal pili promote epithelial colonization but diminish systemic virulence through neutrophil extracellular entrapment.
M1T1 group A streptococcal pili promote epithelial colonization but diminish systemic virulence through neutrophil extracellular entrapment.
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M1T1 A 组链球菌菌毛促进上皮定植，但通过中性粒细胞胞外截留降低全身毒力。
DOI：
10.1007/s00109-009-0566-9
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发表时间：
2010-04
影响因子：
4.7
通讯作者：
Nizet, Victor
中科院分区：
文献类型：
--
作者：
Alexander, Laura E. Crotty;Maisey, Heather C.;Timmer, Anjuli M.;Rooijakkers, Suzan H. M.;Gallo, Richard L.;von Koeckritz-Blickwede, Maren;Nizet, Victor
A组链球菌是与多种粘膜和全身感染相关的主要人类病原体。细胞壁锚定的皮利最近被描述在几种致病性链球菌中，在GAS的情况下，这些表面附属物被证明有利于上皮细胞粘附。在这里，我们使用有针对性的诱变来评估菌毛表达对全球传播的M1 T1 GAS克隆的毒力的贡献，该克隆是GAS咽炎和严重侵袭性感染的主要病原体。我们证实菌毛表达促进GAS粘附到咽部细胞、角质形成细胞和皮肤。然而，与报道的B组链球菌和肺炎球菌皮利的发现相反，我们观察到菌毛表达降低了坏死性筋膜炎、肺炎和脓毒症小鼠模型中的GAS毒力，同时降低了人血液中的GAS存活率。进一步的分析表明，与菌毛表达相关的全身毒力衰减与吞噬细胞摄取、补体沉积或抗菌肽敏感性的差异无关。相反，发现GAS皮利诱导中性粒细胞IL-8产生，促进内皮细胞的中性粒细胞转胞吞作用，并增加基于DNA的细胞外陷阱的中性粒细胞释放，最终促进GAS在这些结构内的截留和杀伤。
Group A Streptococcus is a leading human pathogen associated with a diverse array of mucosal and systemic infections. Cell wall anchored pili were recently described in several species of pathogenic streptococci, and in the case of GAS, these surface appendages were demonstrated to facilitate epithelial cell adherence. Here we use targeted mutagenesis to evaluate the contribution of pilus expression to virulence of the globally disseminated M1T1 GAS clone, the leading agent of both GAS pharyngitis and severe invasive infections. We confirm that pilus expression promotes GAS adherence to pharyngeal cells, keratinocytes, and skin. However, in contrast to findings reported for group B streptococcal and pneumococcal pili, we observe that pilus expression reduces GAS virulence in murine models of necrotizing fasciitis, pneumonia and sepsis, while decreasing GAS survival in human blood. Further analysis indicated the systemic virulence attenuation associated with pilus expression was not related to differences in phagocytic uptake, complement deposition or cathelicidin antimicrobial peptide sensitivity. Rather, GAS pili were found to induce neutrophil IL-8 production, promote neutrophil transcytosis of endothelial cells, and increase neutrophil release of DNA-based extracellular traps, ultimately promoting GAS entrapment and killing within these structures.
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影响因子：
15.3
作者：
LANCEFIELD, RC;DOLE, VP
通讯作者：
DOLE, VP
影响因子：
2.7
作者：
Gupta, AK;Hasler, P;Hahn, S
通讯作者：
Hahn, S
DOI：
10.1073/pnas.0511017103
发表时间：
2006-02-21
影响因子：
11.1
作者：
Barocchi, MA;Rie, J;Henriques-Normark, B
通讯作者：
Henriques-Normark, B
影响因子：
3.6
作者：
Edwards, Andrew M.;Manetti, Andrea G. O.;Grandi, Guido
通讯作者：
Grandi, Guido
影响因子：
15.3
作者：
Bazzoni, F;Cassatella, M A;Rossi, F;Ceska, M;Dewald, B;Baggiolini, M
通讯作者：
Baggiolini, M