CysB-dependent upregulation of the Salmonella Typhimurium cysJIH operon in response to antimicrobial compounds that induce oxidative stress

Alvarez, Ricardo J.; Neumann, German; Frávega, Jorge; Dı́az, Fernando; Tejías, Cristóbal; Collao, Bernardo; Fuentes, Juan A.; Paredes-Sabja, Daniel; Calderón, Iván L.; Gil, Fernando

doi:10.1016/j.bbrc.2015.01.058

Cited by 21 publications

(24 citation statements)

References 33 publications

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“…Typhimurium. This suggests that the modifications in antibiotic resistance previously described in this species [20,34] are not due to the H 2 S itself. In fact, these authors state that the accumulation of H 2 S in their experiments is due to either a decrease in cysteine synthesis or an increase in its catabolism.…”

Section: Discussionsupporting

confidence: 52%

H₂S mediates interbacterial communication through the air reverting intrinsic antibiotic resistance

Thomas‐López

Carrilero

Matrat

et al. 2017

Preprint

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Hydrogen sulfide, a gas classically considered as a by-product of cellular metabolism, is today recognized as a crucial gasotransmitter in Eukaryotes. Moreover, most bacteria harbor the eukaryotic orthologous genes for H2S synthesis, and these genes have been linked to different metabolic pathways.Some bacteria, however, produce high amounts of H2S in their extracellular space, a characteristic classically used for identification purposes. This is the case of Salmonella Typhimurium, which produces H2S by its phsABC operon. Here we show that extracellular release of H2S by S. Typhimurium is solely dependent on its phsABC operon. Furthermore, we show that S. Typhimurium and other H2S-producing bacteria can interact with physically distant bacteria through H2S production. We demonstrate how H2S can revert intrinsic cephalosporin resistance of Enterococccus faecalis and Enterococcus faecium to complete susceptibility. This study constitutes a significant step in the study of bacterial interplay and niche competition. Furthermore, as H2S releasing drugs have already been designed, our results open the way to future therapeutic alternatives for the treatment of infections caused by enterococci, multiresistant pathogens for which no treatments are clinically available.Author SummaryIt has been known for decades that bacteria can communicate with each other through the diffusion of metabolites in the media. However, the capacity of a bacterium to interact with other physically distant cell is a recent discovery of the 21st century. In this work we show how some well-studied bacteria, as it is Salmonella spp., interacts with other bacteria thanks to the compound hydrogen sulfide (H2S) that they produce and release to the environment.In our study we have designed novel techniques that allow us to study the interaction between two bacteria, and we have seen that Salmonella is able to affect other species that is even 1 cm away, i.e., a distance corresponding to 10.0000 times its own size.What is more astonishing is that Enterococcus, when exposed to the H2S, is dramatically becomes susceptible to many antibiotics, to which it is supposed to be naturally resistant. Enterococcus spp. are responsible for life-threatening infections in hospitals worldwide. Thus, our observations reveal that bacteria can communicate through the air with H2S, and that this molecule can make bacteria that are highly resistant to antibiotics susceptible to antibiotics, making untreatable infections treatable with current antibiotics.

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Section: Discussionsupporting

confidence: 52%

H₂S mediates interbacterial communication through the air reverting intrinsic antibiotic resistance

Thomas‐López

Carrilero

Matrat

et al. 2017

Preprint

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“…An alternative hypothesis for the cysteine requirement in the Galleria model is that cysteine serves as a protectant from oxidative and/or nitrosative stresses, which are widely conserved antimicrobial defense strategies. Indeed, cys genes have been linked to increased susceptibility to oxidative stress in several other bacterial species ( 33 – 35 ).…”

Section: Resultsmentioning

confidence: 99%

Joint Transcriptional Control of Virulence and Resistance to Antibiotic and Environmental Stress in Acinetobacter baumannii

Gebhardt

Gallagher

Jacobson

et al. 2015

mBio

116

124

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The increasing emergence of antibiotic-resistant bacterial pathogens represents a serious risk to human health and the entire health care system. Many currently circulating strains of Acinetobacter baumannii exhibit resistance to multiple antibiotics. A key limitation in combating A. baumannii is that our understanding of the molecular mechanisms underlying the pathogenesis of A. baumannii is lacking. To identify potential virulence determinants of a contemporary multidrug-resistant isolate of A. baumannii, we used transposon insertion sequencing (TnSeq) of strain AB5075. A collection of 250,000 A. baumannii transposon mutants was analyzed for growth within Galleria mellonella larvae, an insect-based infection model. The screen identified 300 genes that were specifically required for survival and/or growth of A. baumannii inside G. mellonella larvae. These genes encompass both known, established virulence factors and several novel genes. Among these were more than 30 transcription factors required for growth in G. mellonella. A subset of the transcription factors was also found to be required for resistance to antibiotics and environmental stress. This work thus establishes a novel connection between virulence and resistance to both antibiotics and environmental stress in A. baumannii.

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“…Recently, specific interest has been directed toward sulfur-containing amino acids and global control of cysteine and methionine metabolism in both Gram positive and negative bacteria, such as Lactococcus lactis , Salmonella sp., Vibrio fischeri and Clostridium perfringens ( Fernandez et al, 2002 ; Andre et al, 2010 ; Alvarez et al, 2015 ; Singh et al, 2015 ). Cysteine biosynthesis is the key mechanism by which inorganic sulfur is reduced and incorporated into organic compounds ( Kredich, 1992 ), where it plays an essential role in the formation of the catalytic sites of several enzymes, or protein folding and assembly via the formation of disulfide bonds ( Mihara and Esaki, 2002 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring Amino Acid Auxotrophy in Bifidobacterium bifidum PRL2010

et al. 2015

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The acquisition and assimilation strategies followed by members of the infant gut microbiota to retrieve nitrogen from the gut lumen are still largely unknown. In particular, no information on these metabolic processes is available regarding bifidobacteria, which are among the first microbial colonizers of the human intestine. Here, evaluation of amino acid auxotrophy and prototrophy of Bifidobacterium bifidum, with particular emphasis on B. bifidum strain PRL2010 (LMG S-28692), revealed a putative auxotrophy for cysteine. In addition, we hypothesized that cysteine plays a role in the oxidative stress response in B. bifidum. The use of glutathione as an alternative reduced sulfur compound did not alleviate cysteine auxotrophy of this strain, though it was shown to stimulate expression of the genes involved in cysteine biosynthesis, reminiscent of oxidative stress response. When PRL2010 was grown on a medium containing complex substrates, such as whey proteins or casein hydrolysate, we noticed a distinct growth-promoting effect of these compounds. Transcriptional analysis involving B. bifidum PRL2010 cultivated on whey proteins or casein hydrolysate revealed that the biosynthetic pathways for cysteine and methionine are modulated by the presence of casein hydrolysate. Such findings support the notion that certain complex substrates may act as potential prebiotics for bifidobacteria in their ecological niche.

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CysB-dependent upregulation of the Salmonella Typhimurium cysJIH operon in response to antimicrobial compounds that induce oxidative stress

Cited by 21 publications

References 33 publications

H₂S mediates interbacterial communication through the air reverting intrinsic antibiotic resistance

H₂S mediates interbacterial communication through the air reverting intrinsic antibiotic resistance

Joint Transcriptional Control of Virulence and Resistance to Antibiotic and Environmental Stress in Acinetobacter baumannii

Exploring Amino Acid Auxotrophy in Bifidobacterium bifidum PRL2010

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CysB-dependent upregulation of the Salmonella Typhimurium cysJIH operon in response to antimicrobial compounds that induce oxidative stress

Cited by 21 publications

References 33 publications

H2S mediates interbacterial communication through the air reverting intrinsic antibiotic resistance

H2S mediates interbacterial communication through the air reverting intrinsic antibiotic resistance

Joint Transcriptional Control of Virulence and Resistance to Antibiotic and Environmental Stress in Acinetobacter baumannii

Exploring Amino Acid Auxotrophy in Bifidobacterium bifidum PRL2010

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H₂S mediates interbacterial communication through the air reverting intrinsic antibiotic resistance

H₂S mediates interbacterial communication through the air reverting intrinsic antibiotic resistance