Applied Microbiology and Biotechnology

, Volume 102, Issue 10, pp 4563–4575 | Cite as

Involvement of organic acids and amino acids in ameliorating Ni(II) toxicity induced cell cycle dysregulation in Caulobacter crescentus: a metabolomics analysis

  • Abhishek Jain
  • Wei Ning Chen
Applied microbial and cell physiology


Nickel (Ni(II)) toxicity is addressed by many different bacteria, but bacterial responses to nickel stress are still unclear. Therefore, we studied the effect of Ni(II) toxicity on cell proliferation of α-proteobacterium Caulobacter crescentus. Next, we showed the mechanism that allows C. crescentus to survive in Ni(II) stress condition. Our results revealed that the growth of C. crescentus is severely affected when the bacterium was exposed to different Ni(II) concentrations, 0.003 mM slightly affected the growth, 0.008 mM reduced the growth by 50%, and growth was completely inhibited at 0.015 mM. It was further shown that Ni(II) toxicity induced mislocalization of major regulatory proteins such as MipZ, FtsZ, ParB, and MreB, resulting in dysregulation of the cell cycle. GC-MS metabolomics analysis of Ni(II) stressed C. crescentus showed an increased level of nine important metabolites including TCA cycle intermediates and amino acids. This indicates that changes in central carbon metabolism and nitrogen metabolism are linked with the disruption of cell division process. Addition of malic acid, citric acid, alanine, proline, and glutamine to 0.015 mM Ni(II)-treated C. crescentus restored its growth. Thus, the present work shows a protective effect of these organic acids and amino acids on Ni(II) toxicity. Metabolic stimulation through the PutA/GlnA pathway, accelerated degradation of CtrA, and Ni-chelation by organic acids or amino acids are some of the possible mechanisms suggested to be involved in enhancing C. crescentus’s tolerance. Our results shed light on the mechanism of increased Ni(II) tolerance in C. crescentus which may be useful in bioremediation strategies and synthetic biology applications such as the development of whole cell biosensor.


Caulobacter crescentus Nickel stress Metabolomics Amino acids Organic acids Cell cycle 



The authors would like to thank the Nanyang Environment and Water Research Institute (NEWRI), Singapore, and the Interdisciplinary Graduate School (IGS), Nanyang Technological University, Singapore, for the award of research scholarship to Abhishek Jain and the support for this research. We would also like to thank Asst. Prof. M.H. Tan (Nanyang Technological University) for supplying us strains.

Compliance with ethical standards

Competing interests

The authors declare that they have no conflicts of interest.

Ethical approval

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

Supplementary material

253_2018_8938_MOESM1_ESM.pdf (610 kb)
ESM 1 (PDF 610 kb)


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Copyright information

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

Authors and Affiliations

  1. 1.Interdisciplinary Graduate SchoolNanyang Technological UniversitySingaporeSingapore
  2. 2.Advanced Environmental Biotechnology Centre, Nanyang Environment and Water Research InstituteNanyang Technological UniversitySingaporeSingapore
  3. 3.School of Chemical and Biomedical EngineeringNanyang Technological UniversitySingaporeSingapore

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