Iron-regulated excretion of alpha-keto acids by Salmonella typhimurium

Abstract

Excretion of ␣-keto acids by clinical isolates and laboratory strains of Salmonella typhimurium was determined by high-performance liquid chromatography analysis of culture supernatants. The levels of excretion increased markedly with increasing iron stress imposed by the presence of ␣,␣-dipyridyl or conalbumin in the medium. The major product was pyruvic acid, but significant concentrations of ␣-ketoglutaric acid, ␣-ketoisovaleric acid, and ␣-ketoisocaproic acid were also observed. Maximal excretion occurred at iron stress levels that initially inhibited bacterial growth; the concentration of ␣,␣-dipyridyl at which this was observed differed between strains depending on their ability to secrete and utilize siderophores, suggesting that the intracellular iron status was important in determining ␣-keto acid excretion. However, prolonged incubation of the siderophore-deficient S. typhimurium strain enb-7 under conditions of high iron stress resulted in significant delayed bacterial growth, promoted by tonB-dependent uptake of iron complexed with the high accumulated levels of pyruvic acid and other ␣-keto acids. Strain RB181, a fur derivative of enb-7, excreted massive amounts of ␣-keto acids into the culture medium even in the absence of any iron chelators (the concentration of pyruvic acid, for example, was >25 mM). Moreover, RB181 was able to grow and excrete ␣-keto acids in the presence of ␣,␣-dipyridyl at concentrations threefold greater than that which inhibited the growth of enb-7.

Metabolic Defects Caused by Mutations in the isc Gene Cluster in Salmonella enterica Serovar Typhimurium: Implications for Thiamine Synthesis

“…While it was formally possible that the increased pyruvate in the culture media of isc mutants was simply the result of a metabolic imbalance caused by inactive enzymes (i.e., those containing [Fe-S] centers), the data suggested that this was a regulated response. Pyruvate, as well as other ␣-keto acids, has been associated with iron chelation in many bacterial systems, including S. enterica (17,28,32,43). This was consistent with our observation that pyruvate levels in the medium were altered in response to iron concentration and that this response required the Fur protein.…”

Siderophores in marine coastal waters and their relevance for iron uptake by phytoplankton: experiments with the diatom Phaeodactylum tricornutum

“…MGF production and utilization by S. typhimurium enb-7 has also been observed under certain conditions of iron deficiency (Reissbrodt et al 1997). It is possible that coastal marine bacteria are capable of producing and utilizing the 3 types of siderophores we tested for.…”

“…In bacteria, production and utilization of MGF are induced by low iron concentrations in the medium (Drechsel et al 1993, Reissbrodt et al 1997. However, at least for Phaeodactylum tricornutum, utilization of MGF-bound iron is not influenced by low iron conditions.…”

“…However, other strains such as Escherichia coli show rapid mortality at salinities higher than 25 ppt (Carlucci & Pramer 1959, Ayres 1977, although some faecal coliforms are less affected by salinity ranges from 15 to 40 ppt than at 7 to 15 ppt (Solic & Krstulovic 1992). Recently Reissbrodt et al (1997) has found E. coli and Salmonella typhimurium strains capable of producing α-keto and α-hydroxy acids under different iron-limited conditions. Palenik & Morel (1990) found that marine phytoplankton can produce α-keto acids as a by-product of amino acid utilization.…”

Characterization of secA-sod operon in Borrellia burgdorferi.

“…As stated previously, the growth medium for B. burgdorferi is complex and difficult to manipulate. In the initial investigations with micromolar amounts of Desferal and dipyridyl, inhibition of growth was not consistent with that reported in the literature for other bacteria (Kesavalu et al, 1999;Poole et al, 1996;Reissbrodt et al, 1997). However, growth of Sh-2-82 was inhibited in BSK-II medium plus 10 mM dipyridyl.…”