Incompetence of neutrophils to invasive group A streptococcus is attributed to induction of plural virulence factors by dysfunction of a regulator.
Incompetence of neutrophils to invasive group A streptococcus is attributed to induction of plural virulence factors by dysfunction of a regulator.
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中性粒细胞对侵入性A链球菌的无能归因于调节剂功能障碍诱导复数毒力因子。
DOI：
10.1371/journal.pone.0003455
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Watanabe, Haruo
中科院分区：
文献类型：
--
作者：
Ato, Manabu;Ikebe, Tadayoshi;Kawabata, Hiroki;Takemori, Toshitada;Watanabe, Haruo
A组链球菌(GAS)可引起多种疾病，从普通咽炎到危及生命的严重侵袭性疾病，包括坏死性筋膜炎和链球菌中毒性休克综合征。侵袭性气体感染的特征被认为是由于细菌的遗传变化，然而，由于缺乏一项有趣的研究，使用来自临床严重侵袭性气体感染的血清型匹配的分离株，没有明确的证据。此外，罕见的侵袭性感染及其独特的病理学特征，即没有中性粒细胞渗透的感染灶假设美国侵袭性气体可以逃避宿主防御，特别是中性粒细胞的功能。在此，我们报道了一组临床上从严重侵袭性感染而不是非侵袭性感染中分离出来的血清型匹配的GAS，可以通过至少两种独立的方式消除人多形核中性粒细胞(PMN)的功能：由于促进形成孔洞的毒素链球菌素O(SLO)的产生而导致PMN的坏死，以及由于通过消化PMN的趋化因子白介素8(IL-8)而通过增加丝氨酸蛋白酶SCPC的产生而阻碍PMN的迁移。在ALL emm49严重侵袭性GAS分离株中，由于CSRS基因突变导致抑制功能丧失，基因表达上调。在小鼠模型中，来自临床严重侵袭性气体分离株的CSRS突变体表现出高死亡率和播散性感染，并伴有中性粒细胞稀少，这是人类侵袭性气体感染的特征病理。然而，缺乏SLO或SCPC的GAS对感染小鼠的死亡率明显低于CSRS突变的亲本侵袭性GAS分离株。这些结果表明，GAS对PMN功能的破坏能力可以决定侵袭性GAS感染的发生和严重程度。
Group A streptococcus (GAS) causes variety of diseases ranging from common pharyngitis to life-threatening severe invasive diseases, including necrotizing fasciitis and streptococcal toxic shock-like syndrome. The characteristic of invasive GAS infections has been thought to attribute to genetic changes in bacteria, however, no clear evidence has shown due to lack of an intriguingly study using serotype-matched isolates from clinical severe invasive GAS infections. In addition, rare outbreaks of invasive infections and their distinctive pathology in which infectious foci without neutrophil infiltration hypothesized us invasive GAS could evade host defense, especially neutrophil functions. Herein we report that a panel of serotype-matched GAS, which were clinically isolated from severe invasive but not from non-invaive infections, could abrogate functions of human polymorphnuclear neutrophils (PMN) in at least two independent ways; due to inducing necrosis to PMN by enhanced production of a pore-forming toxin streptolysin O (SLO) and due to impairment of PMN migration via digesting interleukin-8, a PMN attracting chemokine, by increased production of a serine protease ScpC. Expression of genes was upregulated by a loss of repressive function with the mutation of csrS gene in the all emm49 severe invasive GAS isolates. The csrS mutants from clinical severe invasive GAS isolates exhibited high mortality and disseminated infection with paucity of neutrophils, a characteristic pathology seen in human invasive GAS infection, in a mouse model. However, GAS which lack either SLO or ScpC exhibit much less mortality than the csrS-mutated parent invasive GAS isolate to the infected mice. These results suggest that the abilities of GAS to abrogate PMN functions can determine the onset and severity of invasive GAS infection.
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影响因子：
158.5
作者：
Davies, HD;McGeer, A;Naus, M
通讯作者：
Naus, M
影响因子：
30.5
作者：
Ato, M;Stäger, S;Kaye, PM
通讯作者：
Kaye, PM
影响因子：
11.4
作者：
Hidalgo-Grass, Carlos;Mishalian, Inbal;Hanski, Emanuel
通讯作者：
Hanski, Emanuel
影响因子：
3.1
作者：
Kansal, RG;McGeer, A;Kotb, M
通讯作者：
Kotb, M
DOI：
10.1001/jama.1993.03500030088038
发表时间：
1993-01-20
影响因子：
120.7
作者：
BREIMAN, RF;DAVIS, JP;TODD, JK
通讯作者：
TODD, JK