The Cysteine Desulfhydrase CdsH Is Conditionally Required for Sulfur Mobilization to the Thiamine Thiazole in Salmonella enterica

Abstract

Thiamine pyrophosphate is a required coenzyme that contains a mechanistically important sulfur atom. In Salmonella enterica, sulfur is trafficked to both thiamine biosynthesis and 4-thiouridine biosynthesis by the enzyme ThiI using persulfide (R-S-S-H) chemistry. It was previously reported that a thiI mutant strain could grow independent of exogenous thiamine in the presence of cysteine, suggesting there was a second mechanism for sulfur mobilization. Data reported here show that oxidation products of cysteine rescue the growth of a thiI mutant strain by a mechanism that requires the transporter YdjN and the cysteine desulfhydrase CdsH. The data are consistent with a model in which sulfide produced by CdsH reacts with cystine (Cys-S-S-Cys), S-sulfocysteine (Cys-S-SO 3 ؊ ), or another disulfide to form a small-molecule persulfide (R-S-S-H). We suggest that this persulfide replaced ThiI by donating sulfur to the thiamine sulfur carrier protein ThiS. This model describes a potential mechanism used for sulfur trafficking in organisms that lack ThiI but are capable of thiamine biosynthesis.

Perturbation of the metabolic network in Salmonella enterica reveals cross-talk between coenzyme A and thiamine pathways

“…A previous report described ThiC variants (ThiC E281K and ThiC V267M ) that allowed growth on minimal medium, but were unable to support thiamine-independent growth when adenine was added to the growth medium [ 36 ]. The data were consistent with the effect of adenine being to decrease carbon flux through purine biosynthesis, resulting in lower substrate (AIR) concentration for ThiC [ 37 ]. The phenotype of strains carrying the respective thiC alleles appeared similar to that of strains lacking panE in their inability to synthesize thiamine when adenine was present in the medium.…”

H2S and reactive sulfur signaling at the host-bacterial pathogen interface

“…4C) (127). Although rhodanese domains were originally believed to function in cyanide (CN 2 ) detoxification by forming thiocyanide (SCN 2 ) (128), it is well-established that Fe-S cluster biogenesis, molybdenum cofactor biosynthesis, 2-thiouridine synthesis, and thiamine pyrophosphate biosynthesis are known or proposed to use STRs as persulfide transfer catalysts (129)(130)(131)(132)(133). Such "targeted" transsulfuration reactions require specific, albeit likely transient, interactions between donor and acceptor and an exposed active site, as described for TSTD1 and thioredoxin in colon epithelial cells (134).…”

Using axenic and gnotobiotic insects to examine the role of different microbes on the development and reproduction of the kissing bug Rhodnius prolixus (Hemiptera: Reduviidae)

“…encode thiI , but the gene lacks a rhodanase domain which is necessary for sulfurtransferase activity (Martinez-Gomez et al, 2011). In Salmonenlla enterica , YdjN and CdsH have been shown to fulfill the sulfurtransferase role of ThiI (Palmer et al, 2014). D yigB and ybjI are not required for riboflavin synthesis in Rhodococcus or M. luteus but are essential for E. coli riboflavin biosynthesis.…”