The transcription factor SlyA from Salmonella Typhimurium regulates genes in response to hydrogen peroxide and sodium hypochlorite

Cabezas, Carolina; Briones, Alan C.; Aguirre, Camila; Pardo-Esté, Coral; Castro‐Severyn, Juan; Salinas, Cesar; Baquedano, María Soledad; Hidalgo, Alejandro A.; Fuentes, Juan A.; Morales, Eduardo; Meneses, Claudio; Castro-Nallar, Eduardo; Saavedra, Claudia P.

doi:10.1016/j.resmic.2018.04.003

Cited by 22 publications

(14 citation statements)

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“…Other redox sensors primarily known to be involved in ROS resistance have also been described in HOCl response in Gram-negative bacteria. These include the two-component system aerobic respiration control (ArcAB) [ 82 , 143 , 144 ], SylA [ 145 ] and OhrR [ 134 ], which are members of the MarR family, PerR, which belongs to the Fur family [ 70 ], and ComR, controlled by the TetR family [ 70 ].…”

Section: Adaptive Response Of Gram-negative Cells To Hoclmentioning

confidence: 99%

Surviving Reactive Chlorine Stress: Responses of Gram-Negative Bacteria to Hypochlorous Acid

2020

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Sodium hypochlorite (NaOCl) and its active ingredient, hypochlorous acid (HOCl), are the most commonly used chlorine-based disinfectants. HOCl is a fast-acting and potent antimicrobial agent that interacts with several biomolecules, such as sulfur-containing amino acids, lipids, nucleic acids, and membrane components, causing severe cellular damage. It is also produced by the immune system as a first-line of defense against invading pathogens. In this review, we summarize the adaptive responses of Gram-negative bacteria to HOCl-induced stress and highlight the role of chaperone holdases (Hsp33, RidA, Cnox, and polyP) as an immediate response to HOCl stress. We also describe the three identified transcriptional regulators (HypT, RclR, and NemR) that specifically respond to HOCl. Besides the activation of chaperones and transcriptional regulators, the formation of biofilms has been described as an important adaptive response to several stressors, including HOCl. Although the knowledge on the molecular mechanisms involved in HOCl biofilm stimulation is limited, studies have shown that HOCl induces the formation of biofilms by causing conformational changes in membrane properties, overproducing the extracellular polymeric substance (EPS) matrix, and increasing the intracellular concentration of cyclic-di-GMP. In addition, acquisition and expression of antibiotic resistance genes, secretion of virulence factors and induction of the viable but nonculturable (VBNC) state has also been described as an adaptive response to HOCl. In general, the knowledge of how bacteria respond to HOCl stress has increased over time; however, the molecular mechanisms involved in this stress response is still in its infancy. A better understanding of these mechanisms could help understand host-pathogen interactions and target specific genes and molecules to control bacterial spread and colonization.

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Section: Adaptive Response Of Gram-negative Cells To Hoclmentioning

confidence: 99%

Surviving Reactive Chlorine Stress: Responses of Gram-Negative Bacteria to Hypochlorous Acid

2020

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“…Panels show gene expression levels in each strain according to the heatmap scale. Expression data by qRT-PCR were normalized against the expression of talB (Cabezas et al, 2018; Pardo-Esté et al, 2018). Values represent the average of three independent experiments; three technical replicates per experiment.…”

Section: Resultsmentioning

confidence: 99%

“…Fold-change expression of target genes, normalized by the expression of a suitable gene selected in these experimental conditions were calculated as described (Pfaffl, 2011). talB gene expression was used for normalization, since we have validated this gene as showing stable expression under our experimental conditions (Cabezas et al, 2018; Pardo-Esté et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

The Transcription Factor ArcA Modulates Salmonella’s Metabolism in Response to Neutrophil Hypochlorous Acid-Mediated Stress

et al. 2019

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Salmonella Typhimurium, a bacterial pathogen with high metabolic plasticity, can adapt to different environmental conditions; these traits enhance its virulence by enabling bacterial survival. Neutrophils play important roles in the innate immune response, including the production of microbicidal reactive oxygen species (ROS). In addition, the myeloperoxidase in neutrophils catalyzes the formation of hypochlorous acid (HOCl), a highly toxic molecule that reacts with essential biomolecules, causing oxidative damage including lipid peroxidation and protein carbonylation. The bacterial response regulator ArcA regulates adaptive responses to oxygen levels and influences the survival of Salmonella inside phagocytic cells. Here, we demonstrate by whole transcriptomic analyses that ArcA regulates genes related to various metabolic pathways, enabling bacterial survival during HOCl-stress in vitro. Also, inside neutrophils, ArcA controls the transcription of several metabolic pathways by downregulating the expression of genes related to fatty acid degradation, lysine degradation, and arginine, proline, pyruvate, and propanoate metabolism. ArcA also upregulates genes encoding components of the oxidative pathway. These results underscore the importance of ArcA in ATP generation inside the neutrophil phagosome and its participation in bacterial metabolic adaptations during HOCl stress.

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“…We detected a concentration-dependent reduction of growth rate as the CIP concentration was increased, similar to another study with CIP in P. aeruginosa 12 . We then employed RNA-Seq analysis to investigate the influence of a sub-inhibitory CIP concentration on the gene expression of PaeAG1 and its relationship with the bacterial growth, similar to recent studies in P. aeruginosa 76 , 77 and other bacteria 16 , 44 , 78 – 81 . Differential expression analysis (Fig.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic determinants of the response of ST-111 Pseudomonas aeruginosa AG1 to ciprofloxacin identified by a top-down systems biology approach

Molina-Mora

Chinchilla-Montero

Chavarría-Azofeifa

et al. 2020

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Pseudomonas aeruginosa is an opportunistic pathogen that thrives in diverse environments and causes a variety of human infections. Pseudomonas aeruginosa AG1 (PaeAG1) is a high-risk sequence type 111 (ST-111) strain isolated from a Costa Rican hospital in 2010. PaeAG1 has both blaVIM-2 and blaIMP-18 genes encoding for metallo-β-lactamases, and it is resistant to β-lactams (including carbapenems), aminoglycosides, and fluoroquinolones. Ciprofloxacin (CIP) is an antibiotic commonly used to treat P. aeruginosa infections, and it is known to produce DNA damage, triggering a complex molecular response. In order to evaluate the effects of a sub-inhibitory CIP concentration on PaeAG1, growth curves using increasing CIP concentrations were compared. We then measured gene expression using RNA-Seq at three time points (0, 2.5 and 5 h) after CIP exposure to identify the transcriptomic determinants of the response (i.e. hub genes, gene clusters and enriched pathways). Changes in expression were determined using differential expression analysis and network analysis using a topdown systems biology approach. A hybrid model using database-based and co-expression analysis approaches was implemented to predict gene-gene interactions. We observed a reduction of the growth curve rate as the sub-inhibitory cip concentrations were increased. in the transcriptomic analysis, we detected that over time CIP treatment resulted in the differential expression of 518 genes, showing a complex impact at the molecular level. The transcriptomic determinants were 14 hub genes, multiple gene clusters at different levels (associated to hub genes or as co-expression modules) and 15 enriched pathways. Down-regulation of genes implicated in several metabolism pathways, virulence elements and ribosomal activity was observed. in contrast, amino acid catabolism, RpoS factor, proteases, and phenazines genes were up-regulated. Remarkably, > 80 resident-phage genes were up-regulated after CIP treatment, which was validated at phenomic level using a phage plaque assay. thus, reduction of the growth curve rate and increasing phage induction was evidenced as the CIP concentrations were increased. In summary, transcriptomic and network analyses, as well as the growth curves and phage plaque assays provide evidence that PaeAG1 presents a complex, concentration-dependent response to sub-inhibitory CIP exposure, showing pleiotropic effects at the systems level. Manipulation of these determinants, such as phage genes, could be used to gain

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The transcription factor SlyA from Salmonella Typhimurium regulates genes in response to hydrogen peroxide and sodium hypochlorite

Cited by 22 publications

References 50 publications

Surviving Reactive Chlorine Stress: Responses of Gram-Negative Bacteria to Hypochlorous Acid

Surviving Reactive Chlorine Stress: Responses of Gram-Negative Bacteria to Hypochlorous Acid

The Transcription Factor ArcA Modulates Salmonella’s Metabolism in Response to Neutrophil Hypochlorous Acid-Mediated Stress

Transcriptomic determinants of the response of ST-111 Pseudomonas aeruginosa AG1 to ciprofloxacin identified by a top-down systems biology approach

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