非伤寒沙门氏菌(NTS)血清型具有广泛的宿主范围并引起人类胃肠炎。然而,侵袭性NTS(iNTS)血流感染在过去十年中有所增加,每年造成6万人死亡。人类特异性伤寒沙门氏菌在胆结石上定植并形成生物膜,导致慢性,无症状感染。iNTS谱系正在经历基因组减少,可能已经适应了通过毒力突变的人与人之间的传播,胆汁抗性,和生物膜的形成。因此,我们试图在我们的小鼠模型中确定iNTS谱系在胆囊中形成生物膜和发展慢性感染的能力。在测试的谱系(L1、L2、L3和UK)中,只有L2和英国有粗糙的缺陷,干燥和红色(RDAR)形态类型,与已知的bcsG(纤维素)突变相关,但与csgD(curli)基因突变无关。在体外评估生物膜形成能力,这揭示了L3>ST19>UK>L1=L2的生物膜形成层次,这与bcsG或csgD突变均不直接相关。通过共聚焦显微镜,L2和英国的生物膜有明显较少的curli和纤维素,而L1生物膜的纤维素含量明显降低。所有iNTS菌株都能在小鼠胆囊上定殖,肝脏,和脾脏以类似的方式,而L3在胆囊中具有显著较高的细菌负荷和增加的致死率。虽然在生物膜形成中存在iNTS谱系变异性,胆囊定植,和慢性小鼠模型中的毒力,尽管具有生物膜相关突变,但所有测试谱系均能够定殖.因此,iNTS菌株在地方性环境中可能是未被识别的慢性病原体。
Non-typhoidal Salmonella (NTS) serovars have a broad host range and cause gastroenteritis in humans. However, invasive NTS (iNTS) bloodstream infections have increased in the last decade, causing 60,000 deaths annually. Human-specific typhoidal Salmonella colonizes and forms biofilms on gallstones, resulting in chronic, asymptomatic infection. iNTS lineages are undergoing genomic reduction and may have adapted to person-to-person transmission via mutations in virulence, bile resistance, and biofilm formation. As such, we sought to determine the capacity of iNTS lineages for biofilm formation and the development of chronic infections in the gallbladder in our mouse model. Of the lineages tested (L1, L2, L3 and UK), only L2 and UK were defective for the rough, dry and red (RDAR) morphotype, correlating with the known bcsG (cellulose) mutation but not with csgD (curli) gene mutations. Biofilm-forming ability was assessed in vitro, which revealed a biofilm formation hierarchy of L3 > ST19 > UK > L1 = L2, which did not correlate directly with either the bcsG or the csgD mutation. By confocal microscopy, biofilms of L2 and UK had significantly less curli and cellulose, while L1 biofilms had significantly lower cellulose. All iNTS strains were able to colonize the mouse gallbladder, liver, and spleen in a similar manner, while L3 had a significantly higher bacterial load in the gallbladder and increased lethality. While there was iNTS lineage variability in biofilm formation, gallbladder colonization, and virulence in a chronic mouse model, all tested lineages were capable of colonization despite possessing biofilm-related mutations. Thus, iNTS strains may be unrecognized chronic pathogens in endemic settings.