Applied Microbiology and Biotechnology

, Volume 102, Issue 5, pp 2323–2335 | Cite as

4-Hydroxybenzaldehyde sensitizes Acinetobacter baumannii to amphenicols

  • Bora Shin
  • Chulwoo Park
  • James A. Imlay
  • Woojun Park
Applied microbial and cell physiology


Bacterial metabolism modulated by environmental chemicals could alter antibiotic susceptibility. 4-Hydroxybenzaldehyde (4-HBA), which cannot support the growth of Acinetobacter baumannii, exhibited synergism only with amphenicol antibiotics including chloramphenicol (CAM) and thiamphenicol. Interestingly, this synergistic effect was not observed with other growth-supporting, structurally similar compounds such as 4-hydroxybenzoate. Transcriptomic analysis demonstrated that genes involved in protocatechuate metabolism (pca genes) and osmotic stress (bet genes) were significantly upregulated by 4-HBA and CAM treatment. The 14C-labeled CAM influx was lower in a pcaK1 (encoding a transporter of protocatechuate) deletion mutant and was higher in the pcaK1 overexpressing cells relative to that in the wild type upon 4-HBA treatment. Our kinetic data using 14C-labeled CAM clearly showed that CAM uptake is possibly through facilitated diffusion. Deletion of pcaK1 did not result in the elimination of CAM influx, indicating that CAM does not enter only through PcaK1. The amount of 4-HBA in the culture supernatant was, however, unaffected during the test conditions, validating that it was not metabolized by the bacteria. CAM resistant A. baumannii cells derived by serial passages through CAM-amended media exhibited lower level of pcaK1 gene expression. These results led us to conclude that the activation of PcaK1 transporter is probably linked to cellular CAM susceptibility. This is the first report showing a relationship between CAM influx and aromatic compound metabolism in A. baumannii.


Acinetobacter Synergistic compound Plant extract Chloramphenicol Synergism Phenolic compound 4-Hydroxybenzaldehyde 



This work was supported by a National Research Foundation of Korea (NRF) grant to WP funded by the Korean government (MSIP) (No. NRF-2017R1A2B4005838). BS was supported by a Korea University Grant.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2018_8791_MOESM1_ESM.pdf (629 kb)
ESM 1 (PDF 628 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Bora Shin
    • 1
  • Chulwoo Park
    • 1
  • James A. Imlay
    • 2
  • Woojun Park
    • 1
  1. 1.Laboratory of Molecular Environmental Microbiology, Department of Environmental Sciences and Ecological EngineeringKorea UniversitySeoulRepublic of Korea
  2. 2.Department of MicrobiologyUniversity of IllinoisUrbanaUSA

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