Identification of the outer-membrane protein PagC required for the serum resistance phenotype in Salmonella enterica serovar Choleraesuis

Identification of the outer-membrane protein PagC required for the serum resistance phenotype in Salmonella enterica serovar Choleraesuis
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DOI:
10.1099/mic.0.27654-0
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发表时间:
2005-03-01
期刊:
影响因子:
2.8
通讯作者:
Danbara, H
Danbara, H
中科院分区:
生物学4区
文献类型:
--
作者:
Nishio, M;Okada, N;Danbara, H

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血清耐药性是许多病原菌引起全身性感染(包括菌血症)的关键毒力因子。猪霍乱沙门氏菌是一种重要的肠道病原菌,可引起猪和人类严重的全身性感染。在此,发现当导入大肠杆菌时,携带来自S.肠道血清型猪霍乱赋予了对合并的正常猪血清的杀菌活性的高水平抗性。该抗性等于rck赋予的水平,rck是一种编码17 kDa外膜蛋白的基因,可促进链球菌的血清抗性表型。鼠伤寒沙门氏菌插入突变的克隆pagC基因产生的突变,导致在大肠杆菌中的血清抗性表型的损失。将该突变导入S.通过与野生型等位基因的同源重组,将肠霍乱血清型猪霍乱分离,得到的菌株不能产生PagC,并且它显示出对补体介导的杀伤的抗性水平降低。突变可以通过在质粒上引入完整的pagC基因来恢复,但不能通过引入点突变的pagC基因来恢复。此外,PagC还能提高S.肠道血清型猪霍乱LIPS突变株,其对血清杀灭高度敏感。虽然PagC不直接赋予血清抗性,但这些结果强烈地表明PagC是一种重要的外膜蛋白,在S.猪霍乱血清型
Serum resistance is a crucial virulence factor for the development of systemic infections, including bacteraemia, by many pathogenic bacteria. Salmonella enterica serovar Choleraesuis is an important enteric pathogen that causes serious systemic infections in swine and humans. Here, it was found that, when introduced into Escherichia coli, a recombinant plasmid carrying the pagC gene from a plasmid-based genomic library of S. enterica serovar Choleraesuis conferred a high-level resistance to the bactericidal activity of pooled normal swine serum. The resistance was equal to the level conferred by rck, a gene encoding a 17 kDa outer-membrane protein which promotes the serum resistance phenotype in S. enterica serovar Typhimurium. Insertional mutagenesis of the cloned pagC gene generated a mutation that resulted in the loss of the serum resistance phenotype in E coli. When this mutation was introduced into the chromosome of S. enterica serovar Choleraesuis by homology recombination with the wild-type allele, the resulting strain could not produce PagC, and it showed a decreased level of resistance to complement-mediated killing. The mutation could be restored by introduction of the intact pagC gene on a plasmid, but not by introduction of the point-mutated pagC gene. In addition, PagC was able to promote serum resistance in the S. enterica serovar Choleraesuis LIPS mutant strain, which is highly sensitive to serum killing. Although PagC is not thought to confer serum resistance directly, these results strongly suggest that PagC is an important outer-membrane protein that plays an important role in the serum resistance of S. enterica serovar Choleraesuis.