Flavobacterium columnare ferric iron uptake systems are required for virulence

Abstract

Flavobacterium columnare, which causes columnaris disease, is one of the costliest pathogens in the freshwater fish-farming industry. The virulence mechanisms of F. columnare are not well understood and current methods to control columnaris outbreaks are inadequate. Iron is an essential nutrient needed for metabolic processes and is often required for bacterial virulence. F. columnare produces siderophores that bind ferric iron for transport into the cell. The genes needed for siderophore production have been identified, but other components involved in F. columnare iron uptake have not been studied in detail. We identified the genes encoding the predicted secreted heme-binding protein HmuY, the outer membrane iron receptors FhuA, FhuE, and FecA, and components of an ATP binding cassette (ABC) transporter predicted to transport ferric iron across the cytoplasmic membrane. Deletion mutants were constructed and examined for growth defects under iron-limited conditions and for virulence against zebrafish and rainbow trout. Mutants with deletions in genes encoding outer membrane receptors, and ABC transporter components exhibited growth defects under iron-limited conditions. Mutants lacking multiple outer membrane receptors, the ABC transporter, or HmuY retained virulence against zebrafish and rainbow trout mirroring that exhibited by the wild type. Some mutants predicted to be deficient in multiple steps of iron uptake exhibited decreased virulence. Survivors of exposure to such mutants were partially protected against later infection by wild-type F. columnare.

Single-Cell Hemoprotein Diet Changes Adipose Tissue Distributions and Re-Shapes Gut Microbiota in High-Fat Diet-Induced Obese Mice

“…The mechanism by which these bacterial taxa benefit from heme-SCP for their growth is unknown. However, some species of genera Alistipes , Flavobacterium , and Parabacteroides have elaborate mechanisms to scavenge and detoxify iron and heme compounds, such as siderophores, heme-binding proteins, membranous iron receptors, and ferritin-like iron-storage proteins [ 47 - 49 ]. In particular, Roseburia , which thrives in the presence of iron, increases the production of butyrate, a main anti-inflammatory metabolite, in environments with high iron levels [ 50 ].…”

The secretome of the fish pathogen Tenacibaculum maritimum includes soluble virulence-related proteins and outer membrane vesicles

“…Interestingly, it should be noted that in this region of the genome, six more putative TBDTs (A0A5S9TN86, A0A5S9VD89, A0A5S9URM5, A0A5S9TCC5, A0A5S9TBY8, and A0A5S9TCA2) have been identified, being all of them mainly associated with OMVs (Supplementary Table S2). Two other major proteins identified in the T. maritimum secretome were the heme-binding lipoprotein HmuY (A0A5S9RL24) and the TBDT HmuR (A0A5S9RJX3), which was predicted to play a role in heme uptake in other Bacteroidetes species (Conrad et al, 2022;Olczak et al, 2008;Zhu et al, 2022). A homolog of the ferric citrate TBDT FecA (A0A5S9U4N9) and four associated lipoproteins annotated as "Imelysin-like proteins" (A0A5S9RU32, A0A5S9RVE7, A0A5S9RVP5, and A0A5S9U114) were also present in great abundance in the OMV fraction.…”

Supposed Virulence Factors of Flavobacterium psychrophilum: A Review

“…Conversely, BfpR is upregulated when high levels of haemoglobin are present, which may help bacteria adapt to haemoglobin overload during haemorrhagic septicaemia in host fish [96]. FhuA and FecA are siderophore receptors identified in many Gram-negative bacteria, including the related Flavobacterium columnare [109]. In E. coli, FhuA binds catecholate and hydroxamate siderophores, while FecA also binds ferric citrate [110].…”