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

Abstract

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.

Cysteine synthase A overexpression in Corynebacterium glutamicum enhances l‐isoleucine production

“…Modification of the expression levels of ftsZ , sulA , or mreB could improve poly‐3‐hydroxybutyrate production . The cellular metabolism is closely related to the cell division, thus abnormal cell division could result in the rebalance of metabolic flux , and further influence amino acids biosynthesis . The l ‐isoleucine pathway of C. glutamicum IWJ001/pDXW‐8‐ cysK might be influenced by the abnormal cell division caused by CysK overexpression, and more metabolic flux might be drawn toward l ‐isoleucine biosynthesis.…”

A Dual Role of Amino Acids from Sesbania rostrata Seed Exudates in the Chemotaxis Response of Azorhizobium caulinodans ORS571

“…For example, citric acid and oxalic acid have been shown to scavenge metals for soil fungi (Van Hees et al, 2006). Pseudomonas fluorescens produces oxalate to prevent aluminum stress (Hamel et al, 1999), and in Caulobacter crescentus, organic acids prevent nickel toxicity (Jain and Chen, 2018). (5) In addition, oxalic acid can function as a signal molecule and affect competition and pathogenicity in the fungi-bacteria interaction (Rudnick et al, 2015;Ul Haq et al, 2018).…”

Control of proline utilization by the Lrp-like regulator PutR in Caulobacter crescentus

“…The proline amino-acid is not only indispensable for protein synthesis, but also often for osmoprotection or heavy metal tolerance 1 , 2 . In addition, proline can be used as a source of nutrients by bacteria leaving in poor nutrient conditions or in proline-rich host microenvironments 3 .…”

“…The first step of the proline utilization pathway is the conversion of proline into glutamate, to feed the tricarboxylic acid (TCA) or the nitrogen cycles. This conversion requires the sequential action of a proline dehydrogenase (PRODH) and of a Δ 1 -pyrroline-5-carboxylate dehydrogenase (P5CDH). The first of these two oxidation reactions produces reactive oxygen species as frequent by-products 4 – 7 .…”