Huja Sagi, Oren Yaara, Trost Eva, Brzuszkiewicz Elzbieta, Biran Dvora, Blom Jochen, Goesmann Alexander, Gottschalk Gerhard, Hacker Jörg, Ron Eliora Z, Dobrindt Ulrich
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel.
Department of Cell Biology, Tel Aviv University, Tel Aviv, Israel.
mBio. 2015 Jan 13;6(1):e01681-14. doi: 10.1128/mBio.01681-14.
Here we present an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78 that represent the major cause of avian colisepticemia, an invasive infection caused by avian pathogenic Escherichia coli (APEC) strains. It is associated with high mortality and morbidity, resulting in significant economic consequences for the poultry industry. To understand the genetic basis of the virulence of avian septicemic E. coli, we sequenced the entire genome of a clinical isolate of serotype O78-O78:H19 ST88 isolate 789 (O78-9)-and compared it with three publicly available APEC O78 sequences and one complete genome of APEC serotype O1 strain. Although there was a large variability in genome content between the APEC strains, several genes were conserved, which are potentially critical for colisepticemia. Some of these genes are present in multiple copies per genome or code for gene products with overlapping function, signifying their importance. A systematic deletion of each of these virulence-related genes identified three systems that are conserved in all septicemic strains examined and are critical for serum survival, a prerequisite for septicemia. These are the plasmid-encoded protein, the defective ETT2 (E. coli type 3 secretion system 2) type 3 secretion system ETT2sepsis, and iron uptake systems. Strain O78-9 is the only APEC O78 strain that also carried the regulon coding for yersiniabactin, the iron binding system of the Yersinia high-pathogenicity island. Interestingly, this system is the only one that cannot be complemented by other iron uptake systems under iron limitation and in serum.
Avian colisepticemia is a severe systemic disease of birds causing high morbidity and mortality and resulting in severe economic losses. The bacteria associated with avian colisepticemia are highly antibiotic resistant, making antibiotic treatment ineffective, and there is no effective vaccine due to the multitude of serotypes involved. To understand the disease and work out strategies to combat it, we performed an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78, the major cause of the disease. We identified several potential virulence factors, conserved in all the colisepticemic strains examined, and determined their contribution to growth in serum, an absolute requirement for septicemia. These findings raise the possibility that specific vaccines or drugs can be developed against these critical virulence factors to help combat this economically important disease.
在此，我们展示了对血清型O78大肠杆菌菌株的广泛基因组和遗传学分析，这些菌株是禽大肠杆菌败血症的主要病因，禽大肠杆菌败血症是一种由禽致病性大肠杆菌（APEC）菌株引起的侵袭性感染。它与高死亡率和高发病率相关，给家禽业带来重大经济后果。为了解禽败血性大肠杆菌毒力的遗传基础，我们对血清型O78 - O78:H19 ST88分离株789（O78 - 9）的临床分离株的全基因组进行了测序，并将其与三个公开可用的APEC O78序列以及一个APEC血清型O1菌株的完整基因组进行了比较。尽管APEC菌株之间的基因组内容存在很大差异，但仍有几个基因是保守的，这些基因可能对大肠杆菌败血症至关重要。其中一些基因在每个基因组中以多个拷贝存在，或者编码具有重叠功能的基因产物，这表明了它们的重要性。对这些与毒力相关的基因逐一进行系统性缺失分析，确定了在所有检测的败血性菌株中都保守且对血清存活至关重要的三个系统，血清存活是败血症的一个先决条件。这些系统是质粒编码蛋白、有缺陷的ETT2（大肠杆菌3型分泌系统2）3型分泌系统ETT2败血症以及铁摄取系统。菌株O78 - 9是唯一一株还携带编码yersiniabactin（耶尔森菌高致病性岛的铁结合系统）的调节子的APEC O78菌株。有趣的是，在铁限制和血清条件下，该系统是唯一不能被其他铁摄取系统互补的系统。
禽大肠杆菌败血症是禽类的一种严重全身性疾病，导致高发病率和高死亡率，并造成严重经济损失。与禽大肠杆菌败血症相关的细菌具有高度抗生素抗性，使得抗生素治疗无效，而且由于涉及多种血清型，目前尚无有效的疫苗。为了解这种疾病并制定应对策略，我们对该疾病的主要病因血清型O78大肠杆菌菌株进行了广泛的基因组和遗传学分析。我们鉴定了在所有检测的败血性菌株中都保守的几个潜在毒力因子，并确定了它们对血清中生长的贡献，血清生长是败血症的绝对必要条件。这些发现增加了开发针对这些关键毒力因子的特异性疫苗或药物以帮助对抗这种具有经济重要性的疾病的可能性。
