"Limiting access to iron decreases infection of Atlantic salmon SHK-1 cells with bacterium Piscirickettsia salmonis".

Abstract

BACKGROUND:

Vertebrate hosts limit the availability of iron to microbial pathogens in order to nutritionally starve the invaders. The impact of iron deficiency induced by the iron chelator deferoxamine mesylate (DFO) was investigated in Atlantic salmon SHK-1 cells infected with the facultative intracellular bacterium Piscirickettsia salmonis.

RESULTS:

Effects of the DFO treatment and P. salmonis on SHK-1 cells were gaged by assessing cytopathic effects, bacterial load and activity, and gene expression profiles of eight immune biomarkers at 4- and 7-days post infection (dpi) in the control group, groups receiving single treatments (DFO or P. salmonis) and their combination. The chelator appears to be well-tolerated by host cells, while it had a negative impact on the number of bacterial cells and associated cytotoxicity. DFO alone had minor effects on gene expression of SHK-1 cells, including an early activation of IL-1β at 4 dpi. In contrast to few moderate changes induced by single treatments (either infection or chelator), most genes had highest upregulation in the infected groups receiving DFO. The mildest induction of hepcidin-1 (antimicrobial peptide precursor and regulator of iron homeostasis) was observed in cells exposed to DFO alone, followed by P. salmonis infected cells while the addition of DFO to infected cells further increased the mRNA abundance of this gene. Transcripts encoding TNF-α (immune signaling) and iNOS (immune effector) showed sustained increase at both time points in this group while cathelicidin-1 (immune effector) and IL-8 (immune signaling) were upregulated at 7 dpi. The stimulation of protective gene responses seen in infected cultures supplemented with DFO coincided with the reduction of bacterial load and activity (judged by the expression of P. salmonis 16S rRNA), and damage to cultured host cells.

CONCLUSION:

The absence of immune gene activation under normal iron conditions suggests modulation of host responses by P. salmonis. The negative effect of iron deficiency on bacteria likely allowed host cells to respond in a more protective manner to the infection, further decreasing its progression. Presented findings encourage in vivo exploration of iron chelators as a promising strategy against piscirickettsiosis.

• Authors: Rodrigo Díaz, José Troncoso, Eva Jakob, Stanko Skugor
• Journal: BMC veterinary research (BMC Vet Res) Vol. 17 Issue 1 Pg. 155 (Apr 13 2021) ISSN: 1746-6148 [Electronic] England
• PMID: 33849522 (Publication Type: Journal Article)

Chemical References

• Chelating Agents
• Hepcidins
• RNA, Messenger
• Deferoxamine

Topics

• Animals
• Bacterial Load
• Cell Line
• Chelating Agents (pharmacology)
• Deferoxamine (pharmacology)
• Fish Diseases (microbiology)
• Gene Expression Regulation
• Hepcidins (genetics, metabolism)
• Iron Deficiencies
• Piscirickettsia (drug effects, pathogenicity)
• Piscirickettsiaceae Infections (microbiology, veterinary)
• RNA, Messenger (metabolism)
• Salmo salar