The Alternative Electron Acceptor Tetrathionate Supports B ₁₂ -Dependent Anaerobic Growth of Salmonella enterica Serovar Typhimurium on Ethanolamine or 1,2-Propanediol

Abstract

Synthesis of cobalamin de novo by Salmonella enterica serovar Typhimurium strain LT2 and the absence of this ability in Escherichia coli present several problems. This large synthetic pathway is shared by virtually all salmonellae and must be maintained by selection, yet no conditions are known under which growth depends on endogenous B 12 . The cofactor is required for degradation of 1,2-propanediol and ethanolamine. However, cofactor synthesis occurs only anaerobically, and neither of these carbon sources supports anaerobic growth with any of the alternative electron acceptors tested thus far. This paradox is resolved by the electron acceptor tetrathionate, which allows Salmonella to grow anaerobically on ethanolamine or 1,2-propanediol by using endogenously synthesized B 12 . Tetrathionate provides the only known conditions under which simple cob mutants (unable to make B 12 ) show a growth defect. Genes involved in this metabolism include the ttr operon, which encodes tetrathionate reductase. This operon is globally regulated by OxrA (Fnr) and induced anaerobically by a two-component system in response to tetrathionate. Salmonella reduces tetrathionate to thiosulfate, which it can further reduce to H 2 S, by using enzymes encoded by the genes phs and asr. The genes for 1,2-propanediol degradation (pdu) and B 12 synthesis (cob), along with the genes for sulfur reduction (ttr, phs, and asr), constitute more than 1% of the Salmonella genome and are all absent from E. coli. In diverging from E. coli, Salmonella acquired some of these genes unilaterally and maintained others that are ancestral but have been lost from the E. coli lineage.Virtually all Salmonella isolates synthesize B 12 de novo under anaerobic conditions (27,34,43). The ability to synthesize and import B 12 requires more than 35 known genes (48)-approaching 1% of the genome. However, mutations that eliminate B 12 synthesis from otherwise wild-type strains cause no growth defect under the standard aerobic or anaerobic lab conditions used thus far. Since evolutionary maintenance of such a large fraction of the genome requires selection, it seems inescapable that natural conditions must exist under which endogenously synthesized B 12 is important to growth of salmonellae. Salmonella enterica serovar Typhimurium makes B 12 de novo only in the absence of oxygen (27). Degradation of ethanolamine or 1,2-propanediol requires B 12 and provides a carbon and energy source, but growth on these compounds has been observed only under aerobic conditions requiring exogenous B 12 (28,46). These paradoxical aspects of B 12 metabolism have been reviewed (47).The B 12 paradox may be resolved by the finding, described here, that the electron acceptor tetrathionate supports anaerobic use of ethanolamine or 1,2-propanediol as the sole carbon and energy source by using endogenously synthesized B 12 . Under anaerobic conditions, tetrathionate supports considerably better growth on these carbon sources than the other alternative electron acceptors tested. Tetrathionate plu...

Patterns of genome evolution that have accompanied host adaptation in Salmonella

“…Vitamin B12 is required for the anaerobic degradation of 1,2-propanediol, which uses tetrathionate as an electron acceptor (27). Tetrathionate plays an important role in enteric infection: its production is triggered by the inflammatory response to S. Typhimurium in the gut and provides a niche for respiration, in competition with other gut microbes (28).…”

Enhanced levels of λ Red-mediated recombinants in mismatch repair mutants

“…Because ssDNA at the replication fork is bound by Ssb protein (45,46), and Beta protein is important for the interaction between the oligo and the chromosome target, Beta may interact directly and specifically with Ssb (29). The Red system has been shown to work in Salmonella typhimurium (47)(48)(49), a species very closely related to E. coli, and it may also work in other related Gram-negative bacteria. However, for more distantly related bacteria, it may be necessary to provide Beta-like functions from phage endogenous to those bacteria.…”

Specificity of respiratory pathways involved in the reduction of sulfur compounds by Salmonella enterica

“…Expression of the ttrBCA operon requires the TtrSR two-component regulator and is induced by tetrathionate (Hensel et al, 1999 ;Price-Carter et al, 2001). It is probable that tetrathionate is sensed directly by TtrS since thiosulfate, the product of tetrathionate metabolism, does not induce Ttr expression.…”