Format

Send to

Choose Destination
Mol Microbiol. 2019 Apr;111(4):1009-1024. doi: 10.1111/mmi.14205. Epub 2019 Feb 27.

Aurantimycin resistance genes contribute to survival of Listeria monocytogenes during life in the environment.

Author information

1
FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Burgstrasse 37, Wernigerode, 38855, Germany.
2
Department of Microbial Natural Products, Helmholtz Centre for Infection Research and Department of Pharmaceutical Biotechnology, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, Campus E8.1, Saarbrücken, 66123, Germany.
3
German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, 38124, Germany.
4
Department of General Microbiology, University of Göttingen, Grisebachstrasse 8, Göttingen, 37077, Germany.
5
FG13 Nosocomial Pathogens and Antibiotic Resistances, Robert Koch Institute, Burgstrasse 37, Wernigerode, 38855, Germany.

Abstract

Bacteria can cope with toxic compounds such as antibiotics by inducing genes for their detoxification. A common detoxification strategy is compound excretion by ATP-binding cassette (ABC) transporters, which are synthesized upon compound contact. We previously identified the multidrug resistance ABC transporter LieAB in Listeria monocytogenes, a Gram-positive bacterium that occurs ubiquitously in the environment, but also causes severe infections in humans upon ingestion. Expression of the lieAB genes is strongly induced in cells lacking the PadR-type transcriptional repressor LftR, but compounds leading to relief of this repression in wild-type cells were not known. Using RNA-Seq and promoter-lacZ fusions, we demonstrate highly specific repression of the lieAB and lftRS promoters through LftR. Screening of a natural compound library yielded the depsipeptide aurantimycin A - synthesized by the soil-dwelling Streptomyces aurantiacus - as the first known naturally occurring inducer of lieAB expression. Genetic and phenotypic experiments concordantly show that aurantimycin A is a substrate of the LieAB transporter and thus, lftRS and lieAB represent the first known genetic module conferring and regulating aurantimycin A resistance. Collectively, these genes may support the survival of L. monocytogenes when it comes into contact with antibiotic-producing bacteria in the soil.

PMID:
30648305
DOI:
10.1111/mmi.14205

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center