Hydrogen sulfide in physiology and pathogenesis of bacteria and viruses

Pal, Virender Kumar; Bandyopadhyay, Parijat; Singh, Amit

doi:10.1002/iub.1740

Cited by 92 publications

(93 citation statements)

References 191 publications

(221 reference statements)

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“…In a study involving wild-type and H 2 S deficient strains of E.coli, H 2 O 2 degradation in the cell was severely hampered in the mutant strains compared to the wild-type (H 2 S proficient) strains [48]. H 2 S has the ability to antagonize H 2 O 2 effects on the host [49], scavenge reactive oxygen species [50], and induce the expression of catalases and peroxidases [50], all leading to lower amounts of H 2 O 2 in the host.…”

Section: Viral Reactivationmentioning

confidence: 99%

The influence of spaceflight on the astronaut salivary microbiome and the search for a microbiome biomarker for viral reactivation

et al. 2020

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Background: Spaceflight impacts astronauts in many ways but little is known on how spaceflight affects the salivary microbiome and the consequences of these changes on astronaut health, such as viral reactivation. In order to understand this, the salivary microbiome was analyzed with 16S rRNA gene amplicon sequencing, and saliva viral titers were analyzed with quantitative polymerase chain reaction (qPCR) with primers specific for Epstein-Barr virus (EBV), herpes simplex virus (HSV), and varicella zoster virus (VZV) from 10 astronauts pre-flight, in-flight, and postflight. Results: Streptococcus was the most abundant organism in the saliva, making up 8% of the total organisms detected, and their diversity decreased during spaceflight. Other organisms that had statistically significant changes were Proteobacteria and Fusobacteria which increased during flight and Actinobacteria which decreased during flight. At the genus level, Catonella, Megasphera, and Actinobacillus were absent in more than half of saliva samples collected pre-flight but were then detected during flight. In those subjects that already had these genera pre-flight, their relative abundances increased during flight. Correlation analyses between the microbiome and viral titers revealed a positive correlation with Gracilibacteria, Absconditabacteria, and Abiotrophia and a negative correlation between Oribacterium, Veillonella, and Haemophilus. There was also a significant positive correlation between microbiome richness and EBV viral titers. Conclusions: This is the first study to look at how the salivary microbiome changes as a result of spaceflight and the search for bacterial biomarkers for viral reactivation. Further studies examining the role of specific organisms that were shown to be correlative and predictive in viral reactivation, a serious problem in astronauts during spaceflight, could lead to mitigation strategies to help prevent disease during both short and long duration space missions.

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Section: Viral Reactivationmentioning

confidence: 99%

The influence of spaceflight on the astronaut salivary microbiome and the search for a microbiome biomarker for viral reactivation

et al. 2020

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“…In conclusion, we demonstrate that it is indeed possible for non-metallated, dithiol-based transcriptional regulators to achieve a level of specificity required for bacterial cells to trigger a unique response to RSS/H 2 S toxicity rather than general redox misbalance. This is functionally important since increased H 2 S biogenesis has been shown to be necessary for bacteria to counteract the effect of antibiotic stress and host derived reactive oxygen and nitrogen species stressors 4,16,19,42 . We show that this chemical specificity derives from a unique energetic landscape dictated by the protein matrix, which dictates the spectrum of posttranslational modifications by minimizing local structural frustration, while exploiting steric hindrance and low nucleophilicity.…”

Section: Figurementioning

confidence: 99%

Structural determinants of persulfide-sensing specificity in a dithiol-based transcriptional regulator

Capdevila¹,

Walsh²,

Zhang³

et al. 2020

Preprint

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1Cysteine thiol-based transcriptional regulators orchestrate coordinated regulation of redox homeostasis 2 and other cellular processes by "sensing" or detecting a specific redox-active molecule, which in turn 3 activates the transcription of a specific detoxification pathway. The extent to which these sensors are 4 truly specific in cells for a singular class of reactive small molecule stressors, e.g., reactive oxygen or 5 sulfur species, is largely unknown. Here we report novel structural and mechanistic insights into a thiol-6 based transcriptional repressor SqrR, that reacts exclusively with organic and inorganic oxidized sulfur 7 species, e.g., persulfides, to yield a unique tetrasulfide bridge that allosterically inhibits DNA operator-8 promoter binding. Evaluation of five crystallographic structures of SqrR in various derivatized states, 9 coupled with the results of a mass spectrometry-based kinetic profiling strategy, suggest that persulfide 1 0 selectivity is determined by structural frustration of the disulfide form. This energetic roadblock 1 1 effectively decreases the reactivity toward major oxidants to kinetically favor formation of the 1 2 tetrasulfide product. These findings lead to the identification of an uncharacterized repressor from the 1 3 increasingly antibiotic-resistant bacterial pathogen, Acinetobacter baumannii, as a persulfide sensor, 1 4illustrating the predictive power of this work and potential applications to bacterial infectious disease. 1 5 1 6Regulatory posttranslational modifications on thiol groups of redox-active and allosterically important 1 cysteines are a critical component of signaling and redox regulation in cells 1-3 . The successful 2 adaptation of microorganisms to an ever-changing microenvironment depends, to a considerable degree, 3 on the specificity of the regulation of the expression of needed repair enzymes 4-6 . Understanding the 4 extent to which transcriptional regulation is specific to a particular redox-active small molecule(s) is 5 complicated by cross-talk or interconversion among these species in cells 7,8 and the difficulties 6 associated with identifying a posttranslational modification that is biologically meaningful at cell-7 appropriate concentrations that induce a cellular response 9 . Prominent exceptions to this are a handful 8 of transcriptional regulators that employ a metallated cofactor, such as a mononuclear iron 10,11 , an iron-9 sulfur cluster 12,13 or a heme-based sensing moeity 14 ; here, the local inorganic chemistry alone is 1 0 typically sufficient to explain the specificity of these switches toward their inducer 15 . In fact, it remains 1 1 unclear if and how a non-metallated, dithiol-based transcriptional regulator achieves a similar level of 1 2 specificity toward different cellular oxidants.

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“…At physiological pH, H 2 S exists mainly as a hydrosulfide anion (HS − , 75−80%), with the remainder in the form of the dissolved uncharged H 2 S gas (~20−25%) and negligible amounts of S 2− 8 . Here, unless specified, we refer to the sulfide pool (H 2 S + HS − + S 2− ) as H 2 S. H 2 S modulates various physiological functions including inflammation, metabolism, neuroprotection, vasodilation 9 , and protection of microbes against antibiotics 10,11 . Surprisingly, despite having several overlapping functions with CO and •NO 8,12 , a role for host-generated H 2 S in bacterial pathogenesis has not yet been described.…”

mentioning

confidence: 99%

Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis

et al. 2020

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Hydrogen sulfide (H 2 S) is involved in numerous pathophysiological processes and shares overlapping functions with CO and •NO. However, the importance of host-derived H 2 S in microbial pathogenesis is unknown. Here we show that Mtb-infected mice deficient in the H 2 S-producing enzyme cystathionine β-synthase (CBS) survive longer with reduced organ burden, and that pharmacological inhibition of CBS reduces Mtb bacillary load in mice. Highresolution respirometry, transcriptomics and mass spectrometry establish that H 2 S stimulates Mtb respiration and bioenergetics predominantly via cytochrome bd oxidase, and that H 2 S reverses •NO-mediated inhibition of Mtb respiration. Further, exposure of Mtb to H 2 S regulates genes involved in sulfur and copper metabolism and the Dos regulon. Our results indicate that Mtb exploits host-derived H 2 S to promote growth and disease, and suggest that host-directed therapies targeting H 2 S production may be potentially useful for the management of tuberculosis and other microbial infections.

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Hydrogen sulfide in physiology and pathogenesis of bacteria and viruses

Cited by 92 publications

References 191 publications

The influence of spaceflight on the astronaut salivary microbiome and the search for a microbiome biomarker for viral reactivation

The influence of spaceflight on the astronaut salivary microbiome and the search for a microbiome biomarker for viral reactivation

Structural determinants of persulfide-sensing specificity in a dithiol-based transcriptional regulator

Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis

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