The Effect of the Gallbladder Environment during Chronic Infection on Salmonella Persister Cell Formation.

The Effect of the Gallbladder Environment during Chronic Infection on Salmonella Persister Cell Formation.
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DOI:
10.3390/microorganisms10112276
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发表时间:
2022-11-16
期刊:
影响因子:
4.5
通讯作者:
Gunn JS
Gunn JS
中科院分区:
生物学3区
文献类型:
--
作者:
González JF;Hitt R;Laipply B;Gunn JS

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伤寒是由伤寒沙门氏菌(S. Typhi)引起的。大约 3-5% 的感染者成为慢性携带者,其中胆囊 (GB) 是主要的持续存在部位。胆结石 (GS) 有助于 GB 运输的发育和维持,作为沙门氏菌附着并形成生物膜的基质。这种生物膜基质可以保护细菌免受宿主免疫系统和环境压力的影响。这种屏蔽环境是持久细胞发育的理想场所,持久细胞是群体内细胞子集的一种短暂表型,可以在抗生素治疗后存活。持久性也可能因应对 GB 等恶劣环境而出现。在这里,我们调查 GB 条件是否影响沙门氏菌种群中的持续存在数量。为了模拟慢性 GB 环境,我们在牛胆汁或人胆汁存在的情况下在胆固醇包被的 96 孔板中培养生物膜。然后,我们用高浓度的不同抗生素处理浮游或生物膜沙门氏菌培养物。这项研究表明,生物膜为存留细胞提供了一个利基,但 GB 条件要么对存留细胞形成不起作用,要么产生负面影响,特别是在卡那霉素处理后。抗生素靶点很重要,因为针对 DNA 复制或细胞壁的抗菌药物对持久细胞的形成没有影响。有趣的是,用环丙沙星重复治疗增加了生物膜中鼠伤寒沙门氏菌持续存在的百分比,但这种增加被 GB 条件消除了。另一方面,在 GB 条件下重复环丙沙星处理伤寒沙门氏菌生物膜略微增加了持续者的比例。因此,虽然GB中的恶劣条件被认为会导致持续细胞的增加,从而促进慢性携带的发展,但这些数据表明持续细胞的形成在这种环境中受到抑制。
Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi). Around 3–5% of individuals infected become chronic carriers, with the gallbladder (GB) as the predominant site of persistence. Gallstones (GS) aid in the development and maintenance of GB carriage, serving as a substrate to which Salmonellae attach and form a biofilm. This biofilm matrix protects bacteria from the host immune system and environmental stress. This shielded environment is an ideal place for the development of persister cells, a transient phenotype of a subset of cells within a population that allows survival after antibiotic treatment. Persisters can also arise in response to harsh environments such as the GB. Here we investigate if GB conditions affect the number of persisters in a Salmonella population. To simulate the chronic GB environment, we cultured biofilms in cholesterol-coated 96-well plates in the presence of ox or human bile. We then treated planktonic or biofilm Salmonella cultures with high concentrations of different antibiotics. This study suggests that biofilms provide a niche for persister cells, but GB conditions either play no role or have a negative influence on persister formation, especially after kanamycin treatment. The antibiotic target was important, as antimicrobials directed against DNA replication or the cell wall had no effect on persister cell formation. Interestingly, repeated treatment with ciprofloxacin increased the percentage of S. Typhimurium persisters in a biofilm, but this increase was abolished by GB conditions. On the other hand, repeated ciprofloxacin treatment of S. Typhi biofilms in GB conditions slightly increased the fraction of persisters. Thus, while the harsh conditions in the GB would be thought to give rise to increased persisters, therefore contributing to the development of chronic carriage, these data suggest persister cell formation is dampened in this environment.
DOI: 10.1016/j.chom.2021.10.002
发表时间: 2021-12-08
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发表时间: 2013-06-12
影响因子: 30.3
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发表时间: 1986-05-01
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