Indole Inhibits IncP-1 Conjugation System Mainly Through Promoting korA and korB Expression.
Indole Inhibits IncP-1 Conjugation System Mainly Through Promoting korA and korB Expression.
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吲哚主要通过促进korA和korB表达来抑制IncP-1缀合系统
DOI：
10.3389/fmicb.2021.628133
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发表时间：
2021
影响因子：
5.2
通讯作者：
Huang B
中科院分区：
文献类型：
--
作者：
Xiong R;Liu Y;Pu J;Liu J;Zheng D;Zeng J;Chen C;Lu Y;Huang B
吲哚作为一种跨物种信号分子，调节多种生理活动，如抗生素耐药性、耐酸性和毒力。然而，吲哚对偶联反应的影响尚不清楚。本文以大肠杆菌SM10λπ为供体菌株，研究了吲哚对携带庆大霉素抗性的可动员pUCP24T质粒接合的影响。结果表明，外源吲哚处理抑制了pUCP24T从Sm10λπ向受体菌株铜绿假单胞菌PA01和E.ColiEC600的接合转移。此外，通过在SM10λπ中过表达色氨酸酶TNAA来增加内源吲哚的产量，显著地抑制了SM10λπ-PAO1和SM10λπ-EC600的结合，而缺乏TNAA则逆转了表型。随后的机制研究表明，外源吲哚显著抑制交配对形成基因(TrbB)和DNA转移与复制基因(TrfA)的表达，这主要是由于调控基因(Kora和Korb)的促进，这一结果在tna A基因敲除和过表达菌株中得到证实。此外，我们还发现环丙沙星对SM10λπ胞外吲哚合成和TNAA表达均有下调作用。有趣的是，CIP处理的八分之一最低抑制浓度明显促进了Sm10λπ-PAO1和Sm10λπ-EC600的结合，而吲哚抑制了CIP诱导的结合频率。这些数据表明，吲哚可能在CIP诱导的接合过程中起到负面作用。这是首次揭示吲哚抑制结合的生物学功能及其在CIP诱导的结合中的作用，有望发展成为控制抗生素耐药性传播的新途径。
Indole works as an interspecies signal molecule to regulate multiple physiological activities, like antibiotic resistance, acid resistance, and virulence. However, the effect of indole on conjugation is unknown. Here, with Escherichia coli SM10λπ as a donor strain that carries a chromosomally integrated conjugative RP4 plasmid, we explored the effect of indole on conjugation of a mobilizable pUCP24T plasmid imparting gentamycin resistance. The results showed that exogenous indole treatment inhibited conjugative transfer of pUCP24T from SM10λπ to recipient strains, Pseudomonas aeruginosa PAO1 and E. coli EC600. Furthermore, raising endogenous indole production through overexpression of TnaA, a tryptophanase, in SM10λπ significantly inhibited both SM10λπ-PAO1 and SM10λπ-EC600 conjugation, whereas deficiency of tnaA reversed the phenotype. Subsequent mechanistic studies revealed that exogenous indole significantly inhibited the expression of mating pair formation gene (trbB) and the DNA transfer and replication gene (trfA), mainly due to the promotion of regulatory genes (korA and korB), and the result was confirmed in tnaA knockout and overexpression strains. Additionally, we found that both extracellular indole production and tnaA expression of SM10λπ were downregulated by ciprofloxacin (CIP). Intriguingly, one-eighth minimum inhibitory concentration of CIP treatment clearly facilitated both SM10λπ-PAO1 and SM10λπ-EC600 conjugation, and indole inhibited CIP-induced conjugation frequency. These data suggest that indole may play a negative role in the process of CIP-induced conjugation. This is the first study to reveal the biological function of indole-inhibiting conjugation and its role in CIP-induced conjugation, which may be developed into a new way of controlling the spread of antibiotic resistance.
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影响因子：
64.8
作者：
Beaber, JW;Hochhut, B;Waldor, MK
通讯作者：
Waldor, MK
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影响因子：
14.9
作者：
Carballeira JD;González-Pérez B;Moncalián G;de la Cruz F
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影响因子：
2.6
作者：
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ter Kuile, Benno H.
影响因子：
14.9
作者：
BALZER, D;ZIEGELIN, G;LANKA, E
通讯作者：
LANKA, E
影响因子：
3.6
作者：
Hirakawa, H;Inazumi, Y;Yamaguchi, A
通讯作者：
Yamaguchi, A