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Iron acquisition systems for ferric hydroxamates, haemin and haemoglobin in Listeria monocytogenes
Author(s) -
Jin Bo,
Newton Salete M. C.,
Shao Yi,
Jiang Xiaoxu,
Charbit Alain,
Klebba Phillip E.
Publication year - 2006
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2005.05015.x
Subject(s) - enterobactin , ferrichrome , siderophore , biology , escherichia coli , ferric , listeria monocytogenes , microbiology and biotechnology , ferritin , bacteria , biochemistry , virulence , iron binding proteins , intracellular , transferrin , gene , bacterial outer membrane , chemistry , genetics , organic chemistry
Summary Listeria monocytogenes is a Gram‐positive bacterium that causes severe opportunistic infections in humans and animals. We biochemically characterized, for the first time, the iron uptake processes of this facultative intracellular pathogen, and identified the genetic loci encoding two of its membrane iron transporters. Strain EGD‐e used iron complexes of hydroxamates (ferrichrome and ferrichrome A, ferrioxamine B), catecholates (ferric enterobactin, ferric corynebactin) and eukaryotic binding proteins (transferrin, lactoferrin, ferritin, haemoglobin). Quantitative determinations showed 10–100‐fold lower affinity for ferric siderophores ( K m ≈ 1–10 nM) than Gram‐negative bacteria, and generally lower uptake rates. V max for [ 59 Fe]‐enterobactin (0.15 pMol per 10 9 cells per minute) was 400‐fold lower than that of Escherichia coli . For [ 59 Fe]‐corynebactin, V max was also low (1.2 pMol per 10 9 cells per minute), but EGD‐e transported [ 59 Fe]‐apoferrichrome similarly to E. coli ( V max = 24 pMol per 10 9 cells per minute). L. monocytogenes encodes potential Fur‐regulated iron transporters at 2.031 Mb (the fur‐fhu region), 2.184 Mb (the feo region), 2.27 Mb (the srtB region) and 2.499 Mb (designated hupDGC region). Chromosomal deletions in the fur‐fhu and hupDGC regions diminished iron uptake from ferric hydroxamates and haemin/haemoglobin respectively. In the former locus, deletion of fhuD ( lmo1959 ) or fhuC ( lmo1960 ) strongly reduced [ 59 Fe]‐apoferrichrome uptake. Deletion of hupC ( lmo2429 ) eliminated the uptake of haemin and haemoglobin, and decreased the virulence of L. monocytogenes 50‐fold in mice. Elimination of srtB region genes (Δ lmo2185 , Δ lmo2186 , Δ lmo2183 ), both sortase structural genes (Δ srtB , Δ srtA , Δ srtAB ), fur and feoB did not impair iron transport. However, deletion of bacterioferritin (Δ fri , lmo943 ; 0.97 Mb) decreased growth and altered iron uptake: V max of [ 59 Fe]‐corynebactin transport tripled in this strain, whereas that of [ 59 Fe]‐apoferrichrome decreased 20‐fold.