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Resistance elicited by sub-lethal concentrations of ampicillin is partially mediated by quorum sensing in Pseudomonas

Yue Li1, Lexin Xia2, Jian Chen1

  • 1School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310012, China; Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, Hangzhou 310012, China.

Environment International
|May 14, 2021
PubMed

Insights

Antibiotic resistance increases significantly under sub-lethal ampicillin exposure. Quorum sensing (QS) pathways, particularly rhlI/R, contribute to this resistance by upregulating resistance genes.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Antibiotic resistance is a global health crisis.
  • Sub-lethal antibiotic concentrations in the environment can drive resistance evolution.
  • Mechanisms of resistance emergence under such conditions require further elucidation.

Purpose of the Study:

  • To investigate the evolution of ampicillin resistance in *Pseudomonas aeruginosa* under sub-lethal concentrations.
  • To identify genetic mutations associated with resistance.
  • To explore the role of quorum sensing (QS) in antibiotic resistance.

Main Methods:

  • Evolution of *Pseudomonas aeruginosa* PAO1 under varying sub-lethal ampicillin concentrations.
  • DNA sequencing to identify mutations in resistant strains.
  • Transcriptome analysis of *mpl* and *ampD* deletion mutants.
  • Quorum sensing inhibition and signal restoration experiments.

Main Results:

  • Significant increases in ampicillin minimum inhibitory concentration (MIC) observed (5-6 fold and >19 fold).
  • Frequent mutations identified in *mpl* and *ampD* genes.
  • Deletion mutants showed increased expression of QS genes (*lasR*, *rhlI/R*) and *ampC*.
  • Quorum quenching reduced bacterial growth in ampicillin; QS signal restoration recovered higher MICs, particularly for the *rhlI/R* circuit.

Conclusions:

  • Quorum sensing pathways are involved in the evolution of antibiotic resistance.
  • Mutations in *mpl* and *ampD* contribute to ampicillin resistance, partly through QS modulation.
  • Antibiotic resistance is a multifactorial phenotype influenced by genetic mutations and regulatory networks like QS.
Keywords:
AmpicillinPseudomonas aeruginosaQuorum sensingResistance evolutionSub-lethal exposure

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