Delta-like toxin produced by coagulase-negative staphylococci is associated with neonatal necrotizing enterocolitis

Delta-like toxin produced by coagulase-negative staphylococci is associated with neonatal necrotizing enterocolitis
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凝固酶阴性葡萄球菌产生的 Delta 样毒素与新生儿坏死性小肠结肠炎有关

DOI:
10.1128/iai.55.9.2268-2273.1987
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发表时间:
1987
影响因子:
3.1
通讯作者:
J. Dimmick
J. Dimmick
中科院分区:
医学2区
文献类型:
--
作者:
D. Scheifele;G. Bjornson;'. R. A. Dyer;and;J. Dimmick

文献摘要

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坏死性小肠结肠炎(NEC)是一种原因不明的严重新生儿疾病,尽管粪便细菌与某些疾病的暴发有关。我们检查了凝固酶阴性葡萄球菌(CONS)作为可能的病原体。在我们单位,CONS定植于大多数被研究的婴儿的肠道,包括70例NEC病例中的46%(平均浓度,10(9.1)cfu/g大便)。90%以上的测试菌株产生类似于金黄色葡萄球菌三角洲毒素的溶血素。从NEC相关的表皮葡萄球菌分离株中纯化的毒素在大小、生物学特性和抗原性方面与金黄色葡萄球菌的参比Delta毒素相似。这种类似三角洲的毒素是肠道病态的,会导致幼年大鼠肠道内注射的肠管出现粘膜坏死和出血。邻近未暴露的肠管保持正常,注入卵磷脂中和毒素的肠管也是如此。应用一种新的酶联免疫吸附试验(EL ISA)检测了35例CONS患儿的粪便中的Delta样毒素(Tox+)。阳性检测与NEC密切相关。在18例TOX+CONS患儿中,10例阳性(56%),而17例对照婴儿中仅1例阳性(6%,P=0.002)。在NEC患者中,粪便毒素平均浓度为1,012 ng/g。在6个ELISA阳性样本中,每个样本的滤液对成纤维细胞都有明显的毒性,但在所有5个ELISA阴性样本中均未发现毒性。我们的结论是,在一些TOX+CONS的婴儿的肠道中,Delta样毒素被详细阐述,它与NEC的关联表明,这种CONS是肠道疾病。在我们单位,这一机制在最近44例地方性NEC病例中有23%是明显的。
Necrotizing enterocolitis (NEC) is a serious neonatal disorder of uncertain cause, although fecal bacteria have been implicated in some outbreaks. We examined coagulase-negative staphylococci (CONS) as possible etiologic agents. In our unit, CONS colonized the bowels of most infants studied, including 46% of 70 NEC cases (mean concentration, 10(9.1) CFU/g of stool). Over 90% of tested isolates produced a hemolysin resembling delta toxin of Staphylococcus aureus. Toxin purified from a NEC-associated isolate of Staphylococcus epidermidis resembled reference delta toxin from S. aureus in size, biologic properties, and antigenicity. This delta-like toxin was enteropathic, causing mucosal necrosis and hemorrhage in injected loops of the bowels of infant rats. Adjacent, nonexposed bowel remained normal, as did loops injected with lecithin-neutralized toxin. Using a new enzyme-linked immunosorbent assay (ELISA), we detected delta-like toxin in the stools of 11 of 35 infants colonized with CONS positive for delta-like toxin (Tox+). Positive tests were strongly associated with NEC. Of 18 cases with Tox+ CONS, 10 were positive (56%), whereas only 1 of 17 control infants so colonized was positive (6%, P = 0.002). In NEC patients, the mean fecal toxin concentration was 1,012 ng/g. Toxicity to fibroblasts was demonstrable in filtrates of each of six ELISA-positive samples tested but was absent in all five ELISA-negative samples tested. We conclude that delta-like toxin is elaborated in the bowels of some infants with Tox+ CONS, and its association with NEC suggests that such CONS are enteropathic. In our unit, this mechanism was apparent in 23% of 44 recent cases of endemic NEC.