An rfaH Mutant of Salmonella enterica Serovar Typhimurium is Attenuated in Swine and Reduces Intestinal Colonization, Fecal Shedding, and Disease Severity Due to Virulent Salmonella Typhimurium.
An rfaH Mutant of Salmonella enterica Serovar Typhimurium is Attenuated in Swine and Reduces Intestinal Colonization, Fecal Shedding, and Disease Severity Due to Virulent Salmonella Typhimurium.
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DOI：
10.3389/fvets.2014.00009
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发表时间：
2014
影响因子：
3.2
通讯作者：
Lee IS
中科院分区：
文献类型：
--
作者：
Bearson BL;Bearson SM;Kich JD;Lee IS
猪通常是沙门氏菌的无症状携带者，需要采取干预措施来限制猪的定居，以提高食品安全和减少环境污染。我们评估了减毒和潜在的疫苗在猪的沙门氏菌血清型鼠伤寒沙门氏菌突变体的rfaH，基因编码的RfaH antiterminator，防止过早终止长mRNA转录。用野生型S.接种后1天和2天，鼠伤寒杆菌的平均体温（发烧）显着升高; rfaH接种猪则没有（n = 5/组）。在7天试验期间，与野生型接种猪相比，在rfaH接种猪中观察到粪便、扁桃体和盲肠中沙门氏菌显著减少。为了确定用rfaH突变体接种是否可以提供针对野生型S的保护。鼠伤寒杆菌攻击，两组猪（n = 14/组）在6周龄和8周龄时鼻内接种rfaH突变体或PBS安慰剂，并用亲本野生型S. 11周龄鼠伤寒沙门氏菌。攻毒后1天和2天，模拟接种猪的平均体温显著升高，但rfaH接种猪的平均体温未升高。野生型沙门氏菌在攻毒后2天和3天的粪便脱落以及攻毒后7天的肠道组织定殖。与模拟疫苗接种猪相比，rfaH疫苗接种猪中的鼠伤寒沙门氏菌显著减少。使用IDEXX HerdChek猪沙门氏菌检测试剂盒进行的血清学分析表明，接种rfaH突变体不会刺激针对LPS的免疫应答。这些结果表明，用减毒rfaH突变体接种猪可提供针对强毒沙门氏菌攻击的保护。鼠伤寒沙门氏菌，但不干扰沙门氏菌属的畜群水平监测，从而允许区分感染的动物和接种的动物（DIVA）。
Swine are often asymptomatic carriers of Salmonella spp., and interventions are needed to limit colonization of swine to enhance food safety and reduce environmental contamination. We evaluated the attenuation and potential vaccine use in pigs of a Salmonella enterica serovar Typhimurium mutant of rfaH, the gene encoding the RfaH antiterminator that prevents premature termination of long mRNA transcripts. Pigs inoculated with wild-type S. Typhimurium exhibited a significant elevation in average body temperature (fever) at 1 and 2 days post-inoculation; rfaH-inoculated pigs did not (n = 5/group). During the 7-day trial, a significant reduction of Salmonella in the feces, tonsils, and cecum were observed in the rfaH-inoculated pigs compared to wild-type inoculated pigs. To determine whether vaccination with the rfaH mutant could provide protection against wild-type S. Typhimurium challenge, two groups of pigs (n = 14/group) were intranasally inoculated with either the rfaH mutant or a PBS placebo at 6 and 8 weeks of age and challenged with the parental, wild-type S. Typhimurium at 11 weeks of age. The average body temperature was significantly elevated in the mock-vaccinated pigs at 1 and 2 days post-challenge, but not in the rfaH-vaccinated pigs. Fecal shedding at 2 and 3 days post-challenge and colonization of intestinal tract tissues at 7 days post-challenge by wild-type S. Typhimurium was significantly reduced in the rfaH-vaccinated pigs compared to mock-vaccinated pigs. Serological analysis using the IDEXX HerdChek Swine Salmonella Test Kit indicated that vaccination with the rfaH mutant did not stimulate an immune response against LPS. These results indicate that vaccination of swine with the attenuated rfaH mutant confers protection against challenge with virulent S. Typhimurium but does not interfere with herd level monitoring for Salmonella spp., thereby allowing for differentiation of infected from vaccinated animals (DIVA).