Cobalt (II) Chloride Regulates the Invasion and Survival of Brucella abortus 544 in RAW 264.7 Cells and B6 Mice

Abstract

The effects of Cobalt (II) chloride (CoCl2) in the context of Brucella abortus (B. abortus) infection have not been evaluated so far. Firstly, we found that CoCl2 treatment inhibited the phagocytosis of B. abortus into RAW 264.7 cells. The inhibition of bacterial invasion was regulated by F-actin formation and associated with a reduction in the phosphorylation of ERK1/2 and HIF-1α expression. Secondly, the activation of trafficking regulators LAMP1, LAMP2, and lysosomal enzyme GLA at the transcriptional level activated immune responses, weakening the B. abortus growth at 4 h post-infection (pi). The silencing of HIF-1α increased bacterial survival at 24 h pi. At the same time, CoCl2 treatment showed a significant increase in the transcripts of lysosomal enzyme HEXB and cytokine TNF-α and an attenuation of the bacterial survival. Moreover, the enhancement at the protein level of HIF-1α was induced in the CoCl2 treatment at both 4 and 24 h pi. Finally, our results demonstrated that CoCl2 administration induced the production of serum cytokines IFN-γ and IL-6, which is accompanied by dampened Brucella proliferation in the spleen and liver of treated mice, and reduced the splenomegaly and hepatomegaly. Altogether, CoCl2 treatment contributed to host resistance against B. abortus infection with immunomodulatory effects.

Ex vivo expansion of circulating tumour cells (CTCs)

“…CoCl 2 has been widely used as a chemical hypoxia-mimicking agent, to create a “hypoxia-like” state in vitro by stabilizing HIF-1α, which is the master regulator of the cellular adaptive response to hypoxia 39 . Importantly, mononuclear cells did not survive in a hypoxic condition, and even when viable remain adherent to the filter 40 , 41 . This CoCl 2 protocol helps to overcome some of the difficulties involved in culturing and analysing these relatively rare cancer cells 42 .…”

Structures and Properties of a Series of High-Spin [CoII2] Complexes Supported by Ancillary Benzoate, Ortho-Hydroxybenzoate, and Para-Hydroxybenzoate Ligands

“…Cobalt and its related complexes have also numerous inhibitory effects on the bacterial cell, including the synthesis of polysaccharides, enhancement of bacterial cell membrane penetration, blocking of metal binding sites on enzymes, production of glucosyltransferase, cell membrane damage, etc. , Even though a large number of complexes of Zn­(II), Cu­(II), and Fe­(III) showing antibacterial activities are reported in the literature, − a very few Co­(II)-based complexes with antibacterial properties have been explored with mechanistic details. , A majority of reported studies on cobalt have exhibited antibacterial activities either in salt or nanoparticle forms. , There are also evidences that the adaptation capability of bacteria becomes enhanced in the presence of free Co­(II) salt . Consequently, the development of functionalized organo-chelated Co­(II) complexes embodies a potential therapeutic approach for combating the growth of wide-ranging bacterial infections.…”