Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.
Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.
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DOI：
10.1371/journal.ppat.1009209
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发表时间：
2021-01
期刊：
影响因子：
6.7
通讯作者：
Goodman SD
中科院分区：
文献类型：
--
作者：
Devaraj A;González JF;Eichar B;Thilliez G;Kingsley RA;Baker S;Allard MW;Bakaletz LO;Gunn JS;Goodman SD
伤寒沙门氏菌是伤寒的主要病原体；一种导致3-5%个体慢性携带的急性全身性感染。慢性带菌者无症状，难以治疗，是伤寒暴发的宿主。了解导致慢性传播的因素是开发有效解决伤寒的新疗法的关键。在这里，尽管我们通过系统发育分析没有观察到慢性携带分离株的明显聚类，但我们证明慢性分离株在表型上与急性感染分离株不同。与急性感染分离株形成的生物膜相比，慢性携带分离株形成的生物膜明显更厚，生物量更大，与细胞外DNA （eDNA）和DNABII蛋白的相对水平明显更高相关。重要的是，细胞外DNABII蛋白包括整合宿主因子（IHF）和组蛋白样蛋白（HU），它们对细菌生物膜的结构完整性至关重要。在这项研究中，我们证明了体外慢性载体分离物形成的生物膜容易被针对DNABII蛋白的特异性抗体破坏，这是开发治疗慢性载体的成功的第一步。伤寒沙门氏菌是一种人类限制性病原体，是伤寒的主要病原体，伤寒是一种急性全身性感染，每年全球发病率为2100万例。虽然急性感染可通过抗生素解决，但3-5%的个体发展为难以用抗生素解决的慢性携带。这些人中的大多数是疾病进一步传播的宿主。了解急性和慢性携带菌株之间的差异是设计新的靶向方法来破坏携带的关键。在这里，我们证明了慢性携带菌株虽然与急性菌株没有基因特异性差异，但与急性感染菌株形成的生物膜相比，它们形成了更厚的生物膜，细胞外eDNA和DNABII蛋白的相对水平更高。我们还证明了一种针对DNABII蛋白的抗体显著破坏了由慢性载体菌株形成的生物膜，因此支持了该抗体治疗用途的发展，以减轻慢性载体。
Salmonella Typhi is the primary causative agent of typhoid fever; an acute systemic infection that leads to chronic carriage in 3–5% of individuals. Chronic carriers are asymptomatic, difficult to treat and serve as reservoirs for typhoid outbreaks. Understanding the factors that contribute to chronic carriage is key to development of novel therapies to effectively resolve typhoid fever. Herein, although we observed no distinct clustering of chronic carriage isolates via phylogenetic analysis, we demonstrated that chronic isolates were phenotypically distinct from acute infection isolates. Chronic carriage isolates formed significantly thicker biofilms with greater biomass that correlated with significantly higher relative levels of extracellular DNA (eDNA) and DNABII proteins than biofilms formed by acute infection isolates. Importantly, extracellular DNABII proteins include integration host factor (IHF) and histone-like protein (HU) that are critical to the structural integrity of bacterial biofilms. In this study, we demonstrated that the biofilm formed by a chronic carriage isolate in vitro, was susceptible to disruption by a specific antibody against DNABII proteins, a successful first step in the development of a therapeutic to resolve chronic carriage. Salmonella Typhi, a human restricted pathogen is the primary etiologic agent of typhoid fever, an acute systemic infection that has a global incidence of 21 million cases annually. Although the acute infection is resolved by antibiotics, 3–5% of individuals develop chronic carriage that is difficult to resolve with antibiotics. A majority of these indivuals serve as reservoirs for further spread of the disease. Understanding the differences between acute and chronic carrier strains is key to design novel targeted approaches to undermine carriage. Here, we demonstrated that chronic carrier strains although not genotypically distinct from acute strains, formed thicker biofilms with greater relative levels of extracellular eDNA and DNABII proteins than those formed by acute infection isolates. We also demonstrated that an antibody against DNABII proteins significantly disrupted biofilms formed by a chronic carrier strain and therefore supported development of therapeutic use of this antibody to attenuate chronic carriage.
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影响因子：
3.6
作者：
Brockson ME;Novotny LA;Mokrzan EM;Malhotra S;Jurcisek JA;Akbar R;Devaraj A;Goodman SD;Bakaletz LO
通讯作者：
Bakaletz LO
影响因子：
2.6
作者：
Brandstetter, Kathleyn A.;Jurcisek, Joseph A.;Das, Subinoy
通讯作者：
Das, Subinoy
影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
影响因子：
8
作者：
Goodman, S. D.;Obergfell, K. P.;Bakaletz, L. O.
通讯作者：
Bakaletz, L. O.
影响因子：
11.8
作者：
Galanis, E;Wong, DMALF;WHO Global Salm Surv
通讯作者：
WHO Global Salm Surv