Indole-induced reversion of intrinsic multiantibiotic resistance in Lysobacter enzymogenes

Yong Han, Yan Wang, Yameng Yu, Haotong Chen, Yuemao Shen, Liangcheng Du

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Lysobacter species are a group of environmental bacteria that are emerging as a new source of antibiotics. One characteristic of Lysobacter is intrinsic resistance to multiple antibiotics, which had not been studied. To understand the resistance mechanism, we tested the effect of blocking two-component regulatory systems (TCSs) on the antibiotic resistance of Lysobacter enzymogenes, a prolific producer of antibiotics. Upon treatment with LED209, an inhibitor of the widespread TCS QseC/QseB, L. enzymogenes produced a large amount of an unknown metabolite that was barely detectable in the untreated culture. Subsequent structural elucidation by nuclear magnetic resonance (NMR) unexpectedly revealed that the metabolite was indole. Indole production was also markedly induced by adrenaline, a known modulator of QseC/QseB. Next, we identified two TCS genes, L. enzymogenes qseC (Le-qseC) and Le-qseB, in L. enzymogenes and found that mutations of Le-qseC and Le-qseB also led to a dramatic increase in indole production. We then chemically synthesized a fluorescent indole probe that could label the cells. While the Le-qseB (cytoplasmic response regulator) mutant was clearly labeled by the probe, the LeqseC (membrane sensor) mutant was not labeled. It was reported previously that indole can enhance antibiotic resistance in bacteria. Therefore, we tested if the dramatic increase in the level of indole production in L. enzymogenes upon blocking of Le-qseC and Le-qseB would lead to enhanced antibiotic resistance. Surprisingly, we found that indole caused the intrinsically multiantibiotic-resistant bacterium L. enzymogenes to become susceptible. Point mutations at conserved amino acids in Le- QseC also led to antibiotic susceptibility. Because indole is known as an interspecies signal, these findings may have implications.

Original languageEnglish (US)
Article numbere00995-17
JournalApplied and environmental microbiology
Volume83
Issue number17
DOIs
StatePublished - Sep 1 2017

Keywords

  • Indole
  • Intrinsic antibiotic resistance
  • Lysobacter
  • Natural products
  • Twocomponent regulatory systems

ASJC Scopus subject areas

  • Biotechnology
  • Food Science
  • Applied Microbiology and Biotechnology
  • Ecology

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