Thiol Metabolism and Volatile Metabolome of Clostridioides difficile.

Thiol Metabolism and Volatile Metabolome of Clostridioides difficile.
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DOI:
10.3389/fmicb.2022.864587
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发表时间:
2022
影响因子:
5.2
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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艰难梭菌(Clostridioides difficile,以前称为Clostridium difficile)会导致危及生命的肠道感染。细菌的中心代谢强烈影响毒素产生,从而影响感染进程。在这种情况下,挥发性代谢物组的组成和潜在的起源进行了研究,显示了大量的含硫挥发性代谢物。基于气相色谱/质谱(GC/MS)的顶空分析生长的C。difficile 630Δ C10培养物鉴定了105种主要含硫化合物,这些化合物是典型的C.难闻的气味主要成分为2-甲基-1-丙醇、2-甲基-1-丙硫醇、2-甲基-1-丁硫醇、4-甲基-1-戊硫醇及其二硫化物。鉴定出64种含硫挥发物。为了确定它们的生物合成来源,在生长培养基中改变含硫氨基酸甲硫氨酸和半胱氨酸的浓度。在挥发性代谢物谱中观察到的变化表明,半胱氨酸在含硫挥发物的形成中起着至关重要的作用。我们提出,二硫化物是来自半胱氨酸通过形成cystathietrin类似物,这导致相应的硫醇。然后这些硫醇可以被氧化成二硫化物。此外,甲硫氨酸可能有助于通过将甲硫醇整合到二硫化物生物合成中形成短链二硫化物。总之,典型的C。difficile气味的鉴定和第一个假设,他们的生物合成提出。
Clostridioides difficile (previously Clostridium difficile) causes life-threatening gut infections. The central metabolism of the bacterium is strongly influencing toxin production and consequently the infection progress. In this context, the composition and potential origin of the volatile metabolome was investigated, showing a large number of sulfur-containing volatile metabolites. Gas chromatography/mass spectrometry (GC/MS)-based headspace analyses of growing C. difficile 630Δerm cultures identified 105 mainly sulfur-containing compounds responsible of the typical C. difficile odor. Major components were identified to be 2-methyl-1-propanol, 2-methyl-1-propanethiol, 2-methyl-1-butanethiol, 4-methyl-1-pentanethiol, and as well as their disulfides. Structurally identified were 64 sulfur containing volatiles. In order to determine their biosynthetic origin, the concentrations of the sulfur-containing amino acids methionine and cysteine were varied in the growth medium. The changes observed in the volatile metabolome profile indicated that cysteine plays an essential role in the formation of the sulfur-containing volatiles. We propose that disulfides are derived from cysteine via formation of cystathionine analogs, which lead to corresponding thiols. These thiols may then be oxidized to disulfides. Moreover, methionine may contribute to the formation of short-chain disulfides through integration of methanethiol into the disulfide biosynthesis. In summary, the causative agents of the typical C. difficile odor were identified and first hypotheses for their biosynthesis were proposed.
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