Genome-Wide Search for Genes Required for Bifidobacterial Growth under Iron-Limitation.

Noreen Lanigan,Francesca Bottacini,Mary O'Connell Motherway,Douwe Van Sinderen,Pat G Casey

doi:10.3389/fmicb.2017.00964

Noreen Lanigan, Francesca Bottacini + Show 3 more

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https://doi.org/10.3389/fmicb.2017.00964

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Abstract

Bacteria evolved over millennia in the presence of the vital micronutrient iron. Iron is involved in numerous processes within the cell and is essential for nearly all living organisms. The importance of iron to the survival of bacteria is obvious from the large variety of mechanisms by which iron may be acquired from the environment. Random mutagenesis and global gene expression profiling led to the identification of a number of genes, which are essential for Bifidobacterium breve UCC2003 survival under iron-restrictive conditions. These genes encode, among others, Fe-S cluster-associated proteins, a possible ferric iron reductase, a number of cell wall-associated proteins, and various DNA replication and repair proteins. In addition, our study identified several presumed iron uptake systems which were shown to be essential for B. breve UCC2003 growth under conditions of either ferric and/or ferrous iron chelation. Of these, two gene clusters encoding putative iron-uptake systems, bfeUO and sifABCDE, were further characterised, indicating that sifABCDE is involved in ferrous iron transport, while the bfeUO-encoded transport system imports both ferrous and ferric iron. Transcription studies showed that bfeUO and sifABCDE constitute two separate transcriptional units that are induced upon dipyridyl-mediated iron limitation. In the anaerobic gastrointestinal environment ferrous iron is presumed to be of most relevance, though a mutation in the sifABCDE cluster does not affect B. breve UCC2003's ability to colonise the gut of a murine model.

Highlights

Iron is an essential nutrient for most forms of life, having co-evolved with biological systems for billions of years; it is a key element in many redox reactions and is involved in various cellular processes such as DNA replication, nitrogen fixation, nucleotide biosynthesis and the production of various metabolites (Ilbert and Bonnefoy, 2013)
Bifidobacteria are believed to be able to propagate under low iron conditions and are thought to be efficient scavengers of iron, a notion being supported by the finding that certain bifidobacterial species are found in greater numbers under low luminal iron conditions as compared with normal or high luminal iron conditions
Severe iron limitation has a profound effect on B. breve UCC2003, as illustrated by the plethora of genes whose transcription is altered under such iron restrictive conditions and by the number of genes which were identified in the screening of the random mutant library under iron limiting conditions

Summary

Introduction

Iron is an essential nutrient for most forms of life, having co-evolved with biological systems for billions of years; it is a key element in many redox reactions and is involved in various cellular processes such as DNA replication, nitrogen fixation, nucleotide biosynthesis and the production of various metabolites (Ilbert and Bonnefoy, 2013). The ionic forms of iron found in nature represent two interchangeable redox states: ferrous iron (Fe2+) and its more oxidized form ferric iron (Fe3+). These attributes make iron a versatile prosthetic component in many proteins as a biocatalyst or electron carrier (Andrews et al, 2003). Iron availability can vary greatly along the length of the gastrointestinal tract due to its tendency to complex with other molecules and because of its ability to exist in various oxidation states depending on its surrounding environment (Ilbert and Bonnefoy, 2013). Soluble forms of ferric iron may be reduced to ferrous iron upon entry into the cytoplasm, while ferrous citrate or ferrous ascorbate may be taken up directly by (certain components of) the microbiota. Lactate and short chain fatty acid (SCFA) production by the microbiota may cause a modest, possibly localised drop in the pH in the colon resulting in an increase in iron solubility (den Besten et al, 2013)

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