I am thinking why hydrogen sulfide has its effects in the body. For instance, it is one Salmonella's virulence factor. I am not sure if such a balance equations holds

H2O + H2S ←→ ...

Actually, I miss here some factors because I am not understanding the biochemistry enough to answer this. I think H2S can exists in some sort of ionic form. Hydrogen sulfide reminds me of ammonia. I think it inhibits some systems. By which mechanisms?

It is mentioned in many places the empirical effects: signaling functions similar to NO and CO. But I am interested in how this happens. What is the rate of adhesion of H2S to hemoglobin for instance?

H2S can change to sulfite and thiosulfate in mitochondria which are then excreted into urine. I think most of the biological effects are done before these forms. But in which forms?

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    $\begingroup$ According to my preliminary reading around this topic, although production of hydrogen sulphide is used as a convenient method for detecting the presence of pathogenic Salmonella, there is nothing to link this trait with virulence. Do you have a reference for this? $\endgroup$
    – Alan Boyd
    Mar 4, 2014 at 19:18
  • $\begingroup$ You are probably right. I read about this topic in Lange's Medical Microbiology mostly, and I cannot be find any mentioning that directly related to Virulence, but there are mentionings that H2S is related to signalling functions similar to NO and CO, which possibly have virulence roles. $\endgroup$ Mar 5, 2014 at 7:06
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    $\begingroup$ I am not sure about this. I mean, yes it is used to detect sulfide production of Salmonella species (note that not every Salmonella produces H2S), but it is a gasotransmitter in the human body, which has a role for example in regulating immune responses. In small doses it has antiinflammatory effect, while in large doses it has proinflammatory effect. So I think it is possible that H2S is a virulence factor, but it is really hard to find a study about H2S as virulence factor, since it is a relatively new resource area. $\endgroup$
    – inf3rno
    Nov 4, 2014 at 20:07

2 Answers 2


$H_2S$ is the end product of sulfur related respirations (like sulfate respiration, sulfur respiration, etc...).

By aerob (oxygen) respiration the oxygen in $O_2$ has 0 oxidation number, by $CO_2$ the oxygen has -2 oxidation number, so it was reduced while the carbon was oxidized.

By the thiosulfate respiration of Salmonella enterica the following reaction happens by the reduction of thiosulfate: $S_2O_3^{2-} +2H^+ + 2e^- \to HS^- + HSO_3^{-}$. In this case the sulfur in $S_2O_3^{2-}$ has +2 oxidation number while the sulfur in $HS^-$ has -2 oxidation number, so the sulfur was reduced, it was an electron acceptor, just like oxygen by aerob respiration.

So in the case of Salmonella enterica $H_2S$ production is a byproduct of anaerob respiration. It makes growth faster.

Sulfate-reducing bacteria are those bacteria that can obtain energy by oxidizing organic compounds or molecular hydrogen (H2) while reducing sulfate (SO2- 4) to hydrogen sulfide (H2S).1 In a sense, these organisms "breathe" sulfate rather than oxygen in a form of anaerobic respiration.

Salmonella typhimurium produces H2S from thiosulfate or sulfite.

S. enterica uses gut inflammation to enhance its sulfur related respiration to outgrow the resident microbes in the intestinal lumen (microbiota). The inflammation creates tetrathionate $S_4O_6^{2-}$ in which the sulfur has an average oxidation number of +2.5. This tetrathionate is reduced by the tetrathionate reductase into thiosulfate with sulfur having +2 oxidation number. So sulfur related respiration helps to make growth faster in order to colonize the gut.

Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen.

Since $H_2S$ is a gasotransmitter in the human body, there can be other mechanisms which help S. enterica.

  • in small amounts $H_2S$ has anti-inflammatory and anti-apoptotic effects
  • in large amounts $H_2S$ has pro-inflammatory and pro-apoptotic effects

So S. enterica can probably cause inflammation due to killing cells with a fast release of $H_2S$ or prevent inflammation and keep infected cells alive with a slow release of $H_2S$. I found many evidence of the pro-inflammatory theory. By the anti-apoptotic theory I wasn't so lucky, I found only a single review about anti-apoptotic strategies of intracellular pathogens, but it did not mention $H_2S$ production as a possible mechanism. So it might not be true, further studies needed...

In the digestive system, H2S exerts potent anti-inflammatory actions, regulates blood flow and smooth muscle tone, modulates epithelial secretion and promotes healing of ulcers [4, 5].

Hydrogen sulfide (H2S) is the most recent endogenous gasotransmitter that has been reported to serve many physiological and pathological functions in different tissues. Studies over the past decade have revealed that H2S can be synthesized through numerous pathways and its bioavailability regulated through its conversion into different biochemical forms. H2S exerts its biological effects in various manners including redox regulation of protein and small molecular weight thiols, polysulfides, thiosulfate/sulfite, iron-sulfur cluster proteins, and anti-oxidant properties that affect multiple cellular and molecular responses.

Understanding precise pathophysiological signaling mechanisms and the metabolism of H2S is a topic of active research. Unraveling H2S interactions within different tissues, with other biochemical molecules and various signaling mediators is becoming ever more complex.

These results demonstrate that H2S donors can down-regulate adhesion molecule and proinflammatory cytokine expression, therefore identifying H2S, its synthesis enzymes, and molecular targets (e.g., KATP channels) as potential targets for novel anti-inflammatory therapies.

Thus, all of the above findings demonstrate that H2S induces cytoprotection by an anti-apoptotic pathway.

A short course of H2S infusion was associated with reduction of lung and kidney injury. Prolonged infusion did not enhance protection. Systemically, infusion of H2S increased both the pro-inflammatory response during endotoxemia, as demonstrated by increased TNF-α levels, as well as the anti-inflammatory response, as demonstrated by increased IL-10 levels. In LPS-stimulated whole blood of healthy volunteers, co-incubation with H2S had solely anti-inflammatory effects, resulting in decreased TNF-α levels and increased IL-10 levels. Co-incubation with a neutralizing IL-10 antibody partly abrogated the decrease in TNF-α levels. In conclusion, a short course of H2S infusion reduced organ injury during endotoxemia, at least in part via upregulation of IL-10.

H2S causes apoptosis in HPSCs by activating the mitochondrial pathway. It is suggested that H2S might be one of the factors modifying the pathogenesis of pulpitis by causing loss of viability of HPSCs through apoptosis.

The level ofendogenous H2S was increasing along with the infection occurrence and the gradient of infection aggravate. We can presume that endogenous H2S participated in inflammatory reaction of abdominal infection and could be one of the serology index which concerned with the gradient of infection.

The evidences showed that H2S has an obvious effect on colon smooth muscle contraction, and can increase the intestinal movements in slow transmit constipation. Our experiment states that H2S has anti-inflammation effect in prophase of acute peritoneal cavity infection.

H2S is believed to have two contradicting roles in inflammation. It acts as both pro- and anti-inflammatory molecule(9). Li et al. reported that the physiological concentration of H2S has anti-inflammatory effects, while higher concentrations of H2S can produce pro-inflammatory effects(10). The H2S inflammatory role was also studied in different systems. In the gastrointestinal tract, the H2S regulating role functions by activating KATP channels in order to promote the inflammation response(57). The similar H2S function was observed in pancreas(7), but the actual mechanisms are largely unknown. In conclusion, H2S pathway is a possible route for targeting the inflammation treatment. However, much work needs to be done for understanding the mechanisms of the contradictory roles of H2S in inflammation.

Developing evidence suggests that dysbiosis (abnormal microbial composition or function) can contribute to if not cause chronic intestinal inflammation. 5,7 This inflammation can be caused either by an abnormal composition of entericbacteria with an elevated ratio of aggressive vs protective species, defective production of short-chain fatty acids and other protective microbial products, or enhanced production of hydrogen sulfide and nitrates that block butyrate metabolism and disrupt the mucosal barrier.

These results showed that physiological concentrations of H2S can induce apoptosis of PDL cells and HGFs in periodontitis, suggesting that H2S may play an important role in periodontal tissue damage in periodontal diseases.

We have shown that inactivation of H2S producing enzymes (cystathionine beta-synthase, cystathionine gamma lyase, or 3-mercaptopyruvate sulfurtransferase) and NO-synthase in several Gram (+) and Gram (−) bacteria render them highly sensitive to different classes of antibiotics (Gusarov et al., Science 325 (2009) 1380–1384; Shatalin et al. Science 334 (2011) 986–990). We also presented evidence that Bacillus anthracis-derived NO is critical at the early stage of infection (Shatalin et al. PNAS 105 (2008) 1009–1013). Here we show that: (1) cbs/cse and nos mutations change Bacilli global gene transcription profile; (2) apore formation process in cbs/cse and nos mutants of B. anthracis is affected; (3) virulence of cbs/cse and nos mutants of B. anthracis is diminished. These results demonstrate that bacterial H2S and NO are an important virulence factors, and that enzymes generated these gases may serve as an attractive target for antimicrobial therapy.

Btw. there is non-hydrogen sulfide producing S. enterica too, which can probably (no study about this yet) cause salmonellosis. So using thiosulfate as electron acceptor and producing $H_2S$ might not be essential by the infection. (There are other non-sulfur electron acceptors e.g. nitrate, fumarate, etc... for the case of anaerob metabolism.)

Overall hydrogen-sulfide and other gasotransmitters are important virulence factors of many pathogens.

  • $\begingroup$ You are right. This is very new research area (since 2011 most focus put) such that it has not been bound to virulence in any articles. Much discussion about gasotransmitters: en.wikipedia.org/wiki/Gasotransmitter but not reached any major textbooks. Feel, free to update your answer when you hear more about this topic and updates. $\endgroup$ Nov 5, 2014 at 8:28
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    $\begingroup$ @Masi "These results demonstrate that bacterial H2S and NO are an important virulence factors, and that enzymes generated these gases may serve as an attractive target for antimicrobial therapy." - But you are right studies about gasotransmitters and virulence are very rare. Nice question btw., I have not known that gasotransmitters exists until now... :-) $\endgroup$
    – inf3rno
    Nov 5, 2014 at 13:41
  • $\begingroup$ Neither me. I just noticed now that your answer make sense, just because you have this term gasotransmitter. There is no mentioning about them in Mercks' manual nor Harrison. Could not find in any Medical textbooks. $\endgroup$ Nov 5, 2014 at 14:00
  • $\begingroup$ @Masi en.wikipedia.org/wiki/Gasotransmitter it is a pretty old word - since 1981. The discovery that H2S is a gasotransmitter is about a decade old story. $\endgroup$
    – inf3rno
    Nov 5, 2014 at 14:08
  • $\begingroup$ Yes, time is relative. Very little has been done in the research of this topic. No mentioning in any major medical textbooks. Thank you for doing some meta-analysis! It would be helpful to all if you could reorganise your answer and make introduction and summary at the end. Now, the main point can disappear. $\endgroup$ Nov 5, 2014 at 14:11

Alan Boyd's answer

Production of hydrogen sulphide is used as a convenient method for detecting the presence of pathogenic Salmonella, there is nothing to link this with virulence.

which I agree with.


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