The RcsCDB regulatory system plays a crucial role in the protection of Salmonella enterica serovar Typhimurium against oxidative stress

Farizano, Juan V.; Torres, Mariela Analía; Pescaretti, María de Las Mercedes; Delgado, Mònica

doi:10.1099/mic.0.081133-0

Cited by 26 publications

(16 citation statements)

References 38 publications

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“…In drug-tolerant E. coli cells, SOD and catalase have been shown to have a protective function (50). In other gastrointestinal pathogens, such as S. Typhimurium, many genes must be expressed in order to inactivate ROS, in a process controlled by regulons, such as SoxRS, OxyR, S, E, SlyA, and RecA, as well as the Dps protein, which halts bacterial growth under the control of the factor RpoS (51) (Fig. 2).…”

Section: Oxidant Tolerance (Ros Response)mentioning

confidence: 99%

Mechanisms of Bacterial Tolerance and Persistence in the Gastrointestinal and Respiratory Environments

et al. 2018

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SUMMARYPathogens that infect the gastrointestinal and respiratory tracts are subjected to intense pressure due to the environmental conditions of the surroundings. This pressure has led to the development of mechanisms of bacterial tolerance or persistence which enable microorganisms to survive in these locations. In this review, we analyze the general stress response (RpoS mediated), reactive oxygen species (ROS) tolerance, energy metabolism, drug efflux pumps, SOS response, quorum sensing (QS) bacterial communication, (p)ppGpp signaling, and toxin-antitoxin (TA) systems of pathogens, such as , spp., spp., spp., , spp., spp., spp., and , all of which inhabit the gastrointestinal tract. The following respiratory tract pathogens are also considered:, ,, , and Knowledge of the molecular mechanisms regulating the bacterial tolerance and persistence phenotypes is essential in the fight against multiresistant pathogens, as it will enable the identification of new targets for developing innovative anti-infective treatments.

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Section: Oxidant Tolerance (Ros Response)mentioning

confidence: 99%

Mechanisms of Bacterial Tolerance and Persistence in the Gastrointestinal and Respiratory Environments

et al. 2018

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“…The RcsCDB is an unorthodox signaling system which consists of the transmembrane sensor kinases RcsC and RcsD and the response regulator RcsB (Clarke, 2010;Pescaretti Mde et al, 2013). In Salmonella and E. coli, RcsB induces expression of genes involved in capsular polysaccharide synthesis, responses to oxidative stress, resistance to antimicrobial peptides and systemic colonization of mice (Gottesman et al, 1985;Erickson and Detweiler, 2006;Clarke, 2010;Farizano et al, 2014). RcsB represses flagellar motility and virulence genes on the Salmonella Pathogenicity Island II (Gottesman et al, 1985;Wang et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

Involvement of the Rcs regulon in the persistence of SalmonellaTyphimurium in tomatoes

Marvasi

Moraes

Salas-González

et al. 2016

Environ Microbiol Rep

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It is becoming clear that human enteric pathogens, like Salmonella, can efficiently colonize vegetative and reproductive organs of plants. Even though the bacterium's ability to proliferate within plant tissues has been linked to outbreaks of salmonellosis, little is known about regulatory and physiological adaptations of Salmonella, or other human pathogens, to their persistence in plants. A screen of Salmonella deletion mutants in tomatoes identified rcsA and rcsB genes as those under positive selection. In tomato fruits, populations of Salmonella rcsB mutants were as much as 100-fold lower than those of the wild type. In the follow-up experiments, competitive fitness of rcsA and rcsB mutants was strongly reduced in tomatoes. Bioinformatics predictions identified a putative Salmonella RcsAB binding box (TTMGGAWWAABCTYA) and revealed an extensive putative RcsAB regulon, of which many members were differentially fit within tomatoes.

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“…To confirm the SlyA repression effect on rcsB, we used another RcsB-dependent gene, dps (32). When the levels of dps::lacZY transcription were determined, we observed that slyA overexpression decreased dps expression in the wild type but not in the rcsB strain (Fig.…”

Section: Figmentioning

confidence: 91%

Regulatory Effect of SlyA on rcsB Expression in Salmonella enterica Serovar Typhimurium

et al. 2019

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The Salmonella enterica serovar Typhimurium RcsCDB system regulates the synthesis of colanic acid and the flagellum as well as the expression of virulence genes. We previously demonstrated that the rcsC11 mutant, which constitutively activates the RcsB regulator, attenuates Salmonella virulence in an animal model. This attenuated phenotype was also produced by deletion of the slyA gene. In this work, we investigated if this antagonistic behavior is produced by modulating the expression of both regulator-encoding genes. We demonstrated that SlyA overproduction negatively regulates rcsB transcription. A bioinformatics analysis enabled us to identify putative SlyA binding sites on both promoters, PrcsDB and PrcsB, which control rcsB transcriptional levels. We also determined that SlyA is able to recognize and bind to these predicted sites to modulate the activity of both rcsB promoters. According to these results, SlyA represses rcsB transcription by direct binding to specific sites located on the rcsB promoters, thus accounting for the attenuated/virulence antagonistic behaviors. Moreover, we showed that the opposite effect between both regulators also physiologically affects the Salmonella motility phenotype. In this sense, we observed that under SlyA overproduction, PrcsB is repressed, and consequently, bacterial motility is increased. On the basis of these results, we suggest that during infection, the different RcsB levels produced act as a switch between the virulent and attenuated forms of Salmonella. Thereby, we propose that higher concentrations of RcsB tilt the balance toward the attenuated form, while absence or low concentrations resulting from SlyA overproduction tilt the balance toward the virulent form. IMPORTANCE The antagonistic behavior of RcsB and SlyA on virulence gene expression led us to hypothesize that there is interplay between both regulators in a regulatory network and these could be considered coordinators of this process. Here, we report that the SlyA virulence factor influences motility behavior by controlling rcsB transcription from the PrcsB promoter. We also demonstrate that SlyA negatively affects the expression of the rcsB gene by direct binding to PrcsDB and PrcsB promoters. We suggest that different levels of RcsB act as a switch between the virulent and attenuated forms of Salmonella, where high concentrations of the regulator tend to tilt the balance toward the attenuated form and low concentrations or its absence tilt it toward the virulent form.

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The RcsCDB regulatory system plays a crucial role in the protection of Salmonella enterica serovar Typhimurium against oxidative stress

Cited by 26 publications

References 38 publications

Mechanisms of Bacterial Tolerance and Persistence in the Gastrointestinal and Respiratory Environments

Mechanisms of Bacterial Tolerance and Persistence in the Gastrointestinal and Respiratory Environments

Involvement of the Rcs regulon in the persistence of SalmonellaTyphimurium in tomatoes

Regulatory Effect of SlyA on rcsB Expression in Salmonella enterica Serovar Typhimurium

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