scholarly journals The Cellular Response to Lanthanum Is Substrate Specific and Reveals a Novel Route for Glycerol Metabolism in Pseudomonas putida KT2440

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Matthias Wehrmann ◽  
Maxime Toussaint ◽  
Jens Pfannstiel ◽  
Patrick Billard ◽  
Janosch Klebensberger
Keyword(s):  
Pseudomonas Putida ◽  
Cellular Response ◽  
Physiological Role ◽  
Physiological Traits ◽  
Glycerol Metabolism ◽  
Methylotrophic Bacteria ◽  
Environmental Implications ◽  
Glycerate Kinase ◽  
Content Type

ABSTRACT Ever since the discovery of the first rare earth element (REE)-dependent enzyme, the physiological role of lanthanides has become an emerging field of research due to the environmental implications and biotechnological opportunities. In Pseudomonas putida KT2440, the two pyrroloquinoline quinone-dependent alcohol dehydrogenases (PQQ-ADHs) PedE and PedH are inversely regulated in response to REE availability. This transcriptional switch is orchestrated by a complex regulatory network that includes the PedR2/PedS2 two-component system and is important for efficient growth on several alcoholic volatiles. To study whether cellular responses beyond the REE switch exist, the differential proteomic responses that occur during growth on various model carbon sources were analyzed. Apart from the Ca2+-dependent enzyme PedE, the differential abundances of most identified proteins were conditional. During growth on glycerol—and concomitant with the proteomic changes—lanthanum (La3+) availability affected different growth parameters, including the onset of logarithmic growth and final optical densities. Studies with mutant strains revealed a novel metabolic route for glycerol utilization, initiated by PedE and/or PedH activity. Upon oxidation to glycerate via glyceraldehyde, phosphorylation by the glycerate kinase GarK most likely yields glycerate-2-phosphate, which is eventually channeled into the central metabolism of the cell. This new route functions in parallel with the main degradation pathway encoded by the glpFKRD operon and provides a growth advantage to the cells by allowing an earlier onset of growth with glycerol as the sole source of carbon and energy. IMPORTANCE The biological role of REEs has long been underestimated, and research has mainly focused on methanotrophic and methylotrophic bacteria. We have recently demonstrated that P. putida, a plant growth-promoting bacterium that thrives in the rhizosphere of various food crops, possesses a REE-dependent alcohol dehydrogenase (PedH), but knowledge about REE-specific effects on physiological traits in nonmethylotrophic bacteria is still scarce. This study demonstrates that the cellular response of P. putida to lanthanum (La3+) is mostly substrate specific and that La3+ availability highly affects the growth of cells on glycerol. Further, a novel route for glycerol metabolism is identified, which is initiated by PedE and/or PedH activity and provides a growth advantage to this biotechnologically relevant organism by allowing a faster onset of growth. Overall, these findings demonstrate that lanthanides can affect physiological traits in nonmethylotrophic bacteria and might influence their competitiveness in various environmental niches.

scholarly journals The cellular response towards lanthanum is substrate specific and reveals a novel route for glycerol metabolism inPseudomonas putidaKT2440

2019 ◽  
Author(s):  
Matthias Wehrmann ◽  
Maxime Toussaint ◽  
Jens Pfannstiel ◽  
Patrick Billard ◽  
Janosch Klebensberger
Keyword(s):  
Rare Earth ◽  
Cellular Response ◽  
Physiological Role ◽  
Physiological Traits ◽  
Glycerol Metabolism ◽  
Methylotrophic Bacteria ◽  
Environmental Implications ◽  
Glycerate Kinase ◽  
Proteomic Approach

AbstractEver since the discovery of the first rare earth element (REE)-dependent enzyme, the physiological role of lanthanides has become an emerging field of research due to the potential environmental implications and biotechnological opportunities. InPseudomonas putidaKT2440, the two pyrroloquinoline quinone-dependent alcohol dehydrogenases (PQQ-ADHs) PedE and PedH are inversely produced in response to La3+-availability. This REE-switch is orchestrated by a complex regulatory network including the PedR2/PedS2 two-component system and is important for efficient growth on several alcoholic volatiles. AsP. putidais exposed to a broad variety of organic compounds in its natural soil habitat, the cellular responses towards La3+during growth on various carbon and energy sources were investigated with a differential proteomic approach. Apart from the Ca2+-dependent enzyme PedE, the differential abundance of most other identified proteins was conditional and revealed a substrate specificity. Concomitant with the proteomic changes, La3+had a beneficial effect on lag-phases while causing reduced growth rates and lower optical densities in stationary phase during growth on glycerol. When these growth phenotypes were evaluated with mutant strains, a novel metabolic route for glycerol utilization was identified that seems to be functional in parallel with the main degradation pathway encoded by theglpFKRDoperon. The newly discovered route is initiated by PedE and/or PedH, which most likely convert glycerol to glyceraldehyde. In the presence of lanthanum, glyceraldehyde seems to be further oxidized to glycerate, which, upon phosphorylation to glycerate-2-phosphate by the glycerate kinase GarK, is finally channelled into the central metabolism.ImportanceThe biological role of rare earth elements has long been underestimated and research has mainly focused on methanotrophic bacteria. We have recently demonstrated thatP. putida,a plant growth promoting bacterium that thrives in the rhizosphere of various feed crops, possesses a REE-dependent alcohol dehydrogenase (PedH), but knowledge about lanthanide-dependent effects on physiological traits in non-methylotrophic bacteria is still scarce. This study demonstrates that the cellular response ofP. putidaKT2440 towards La3+is mostly substrate specific and that during growth on glycerol, La3+has a severe effect on several growth parameters. We provide compelling evidence that the observed physiological changes are linked to the catalytic activity of PedH and thereby identify a novel route for glycerol metabolism in this biotechnological relevant organism. Overall, these findings demonstrate that lanthanides can alter important physiological traits of non-methylotrophic bacteria, which might consequently influence their competitiveness during colonization of various environmental niches.

scholarly journals Phosphoserine Phosphatase Is Required for Serine and One-Carbon Unit Synthesis in Hydrogenobacter thermophilus

2017 ◽  
Vol 199 (21) ◽  
Author(s):  
Keugtae Kim ◽  
Yoko Chiba ◽  
Azusa Kobayashi ◽  
Hiroyuki Arai ◽  
Masaharu Ishii
Keyword(s):  
Physiological Role ◽  
Tca Cycle ◽  
Content Type ◽  
Phosphoserine Phosphatase ◽  
Genes Encoding ◽  
Hydrogenobacter Thermophilus ◽  
Glycine Cleavage ◽  
Major Donor ◽  
Serine Biosynthesis

ABSTRACT Hydrogenobacter thermophilus is an obligate chemolithoautotrophic bacterium of the phylum Aquificae and is capable of fixing carbon dioxide through the reductive tricarboxylic acid (TCA) cycle. The recent discovery of two novel-type phosphoserine phosphatases (PSPs) in H. thermophilus suggests the presence of a phosphorylated serine biosynthesis pathway; however, the physiological role of these novel-type metal-independent PSPs (iPSPs) in H. thermophilus has not been confirmed. In the present study, a mutant strain with a deletion of pspA, the catalytic subunit of iPSPs, was constructed and characterized. The generated mutant was a serine auxotroph, suggesting that the novel-type PSPs and phosphorylated serine synthesis pathway are essential for serine anabolism in H. thermophilus. As an autotrophic medium supplemented with glycine did not support the growth of the mutant, the reversible enzyme serine hydroxymethyltransferase does not appear to synthesize serine from glycine and may therefore generate glycine and 5,10-CH2-tetrahydrofolate (5,10-CH2-THF) from serine. This speculation is supported by the lack of glycine cleavage activity, which is needed to generate 5,10-CH2-THF, in H. thermophilus. Determining the mechanism of 5,10-CH2-THF synthesis is important for understanding the fundamental anabolic pathways of organisms, because 5,10-CH2-THF is a major one-carbon donor that is used for the synthesis of various essential compounds, including nucleic and amino acids. The findings from the present experiments using a pspA deletion mutant have confirmed the physiological role of iPSPs as serine producers and show that serine is a major donor of one-carbon units in H. thermophilus. IMPORTANCE Serine biosynthesis and catabolism pathways are intimately related to the metabolism of 5,10-CH2-THF, a one-carbon donor that is utilized for the biosynthesis of various essential compounds. For this reason, determining the mechanism of serine synthesis is important for understanding the fundamental anabolic pathways of microorganisms. In the present study, we experimentally confirmed that a novel phosphoserine phosphatase in the obligate chemolithoautotrophic bacterium Hydrogenobacter thermophilus is essential for serine biosynthesis. This finding indicates that serine is synthesized from an intermediate of gluconeogenesis in H. thermophilus. In addition, because glycine cleavage system activity and genes encoding an enzyme capable of producing 5,10-CH2-THF were not detected, serine appears to be the major one-carbon donor to tetrahydrofolate (THF) in H. thermophilus.

scholarly journals Importance of Bacillithiol in the Oxidative Stress Response of Staphylococcus aureus

2013 ◽  
Vol 82 (1) ◽  
pp. 316-332 ◽  
Author(s):  
Ana C. Posada ◽  
Stacey L. Kolar ◽  
Renata G. Dusi ◽  
Patrice Francois ◽  
Alexandra A. Roberts ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Physiological Role ◽  
Content Type ◽  
Chromatography Analysis ◽  
Expression Of Genes ◽  
Fold Reduction ◽  
Fosfomycin Resistance ◽  
Microarray Analyses

ABSTRACTInStaphylococcus aureus, the low-molecular-weight thiol called bacillithiol (BSH), together with cognateS-transferases, is believed to be the counterpart to the glutathione system of other organisms. To explore the physiological role of BSH inS. aureus, we constructed mutants with the deletion ofbshA(sa1291), which encodes the glycosyltransferase that catalyzes the first step of BSH biosynthesis, andfosB(sa2124), which encodes a BSH-S-transferase that confers fosfomycin resistance, in severalS. aureusstrains, including clinical isolates. Mutation offosBorbshAcaused a 16- to 60-fold reduction in fosfomycin resistance in theseS. aureusstrains. High-pressure liquid chromatography analysis, which quantified thiol extracts, revealed some variability in the amounts of BSH present acrossS. aureusstrains. Deletion offosBled to a decrease in BSH levels. ThefosBandbshAmutants of strain COL and a USA300 isolate, upon further characterization, were found to be sensitive to H2O2and exhibited decreased NADPH levels compared with those in the isogenic parents. Microarray analyses of COL and the isogenicbshAmutant revealed increased expression of genes involved in staphyloxanthin synthesis in thebshAmutant relative to that in COL under thiol stress conditions. However, thebshAmutant of COL demonstrated decreased survival compared to that of the parent in human whole-blood survival assays; likewise, the naturally BSH-deficient strain SH1000 survived less well than its BSH-producing isogenic counterpart. Thus, the survival ofS. aureusunder oxidative stress is facilitated by BSH, possibly via a FosB-mediated mechanism, independently of its capability to produce staphyloxanthin.

scholarly journals Taxis of Pseudomonas putida F1 toward Phenylacetic Acid Is Mediated by the Energy Taxis Receptor Aer2

2013 ◽  
Vol 79 (7) ◽  
pp. 2416-2423 ◽  
Author(s):  
Rita A. Luu ◽  
Benjamin J. Schneider ◽  
Christie C. Ho ◽  
Vasyl Nesteryuk ◽  
Stacy E. Ngwesse ◽  
...  
Keyword(s):  
Pseudomonas Putida ◽  
Phenylacetic Acid ◽  
Environmental Pollutants ◽  
Bacterial Chemotaxis ◽  
Degradation Pathway ◽  
Content Type ◽  
E Coli ◽  
Energy Taxis ◽  
System A

ABSTRACTThe phenylacetic acid (PAA) degradation pathway is a widely distributed funneling pathway for the catabolism of aromatic compounds, including the environmental pollutants styrene and ethylbenzene. However, bacterial chemotaxis to PAA has not been studied. The chemotactic strainPseudomonas putidaF1 has the ability to utilize PAA as a sole carbon and energy source. We identified a putative PAA degradation gene cluster (paa) inP. putidaF1 and demonstrated that PAA serves as a chemoattractant. The chemotactic response was induced during growth with PAA and was dependent on PAA metabolism. A functionalcheAgene was required for the response, indicating that PAA is sensed through the conserved chemotaxis signal transduction system. AP. putidaF1 mutant lacking the energy taxis receptor Aer2 was deficient in PAA taxis, indicating that Aer2 is responsible for mediating the response to PAA. The requirement for metabolism and the role of Aer2 in the response indicate thatP. putidaF1 uses energy taxis to detect PAA. We also revealed that PAA is an attractant forEscherichia coli; however, a mutant lacking a functional Aer energy receptor had a wild-type response to PAA in swim plate assays, suggesting that PAA is detected through a different mechanism inE. coli. The role of Aer2 as an energy taxis receptor provides the potential to sense a broad range of aromatic growth substrates as chemoattractants. Since chemotaxis has been shown to enhance the biodegradation of toxic pollutants, the ability to sense PAA gradients may have implications for the bioremediation of aromatic hydrocarbons that are degraded via the PAA pathway.

scholarly journals Crystal structures of γ-glutamyltranspeptidase in complex with inhibitors

2014 ◽  
Vol 70 (a1) ◽  
pp. C847-C847
Author(s):  
Kei Hirabayashi ◽  
Tomoyo Ida ◽  
Chunjie Li ◽  
Hideyuki Suzuki ◽  
Keiichi Fukuyama ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Cellular Response ◽  
Physiological Role ◽  
Time Lapse ◽  
Binding Mode ◽  
E Coli ◽  
Glutathione Biosynthesis ◽  
Intracellular Glutathione ◽  
H Pylori

γ-Glutamyltranspeptidase (GGT; EC 2.3.2.2) is involved in the degradation of γ-glutamyl compounds such as glutathione (GSH; γ-glutamyl-cysteinyl-glycine) . A major physiological role of this enzyme is to cleave the extracellular GSH as a source of cysteine for intracellular glutathione biosynthesis. Another crucial role of GGT is to cleave glutathione-S-conjugates as a key step in detoxification of xenobiotics and drug metabolism. In mammals, GGT has been implicated in physiological disorders such as Parkinson's disease, other neurodegenerative diseases including Alzheimer's disease and cardiovascular disease. The indispensable roles played by GGT in GSH-mediated detoxification and cellular response to oxidative stress suggest that GGT is an attractive pharmaceutical target. We here report the binding mode of acivicin, a well-known glutamine antagonist, to B. subtilis GGT at 1.8 Å resolution showing that acivicin is bound to the Oγ atom of Thr403, the catalytic nucleophile of the enzyme, through its C3 atom [1]. The observed electron density around the C3 atom was best fitted to the planar and sp2 hybridized carbon, consistent with a simple nucleophilic substitution of Cl at the imino carbon by Oγ atom of Thr403. Furthermore, comparison of three bacterial enzymes, the GGTs from E. coli, H. pylori and B. subtilis in complex with acivicin, showed significant diversity in the orientation of the dihydroisoxazole ring among three GGTs. The differences are discussed in terms of the recognition of the α-amino and α-carboxy groups in preference to the dihydroisoxazole ring as observed in time-lapse soaking crystal structures of B. subtilis GGT with acivicin.

scholarly journals Role of N,N-Dimethylglycine and Its Catabolism to Sarcosine in Chromohalobacter salexigens DSM 3043

2020 ◽  
Vol 86 (17) ◽  
Author(s):  
Ting Yang ◽  
Ya-Hui Shao ◽  
Li-Zhong Guo ◽  
Xiang-Lin Meng ◽  
Hao Yu ◽  
...  
Keyword(s):  
Glycine Betaine ◽  
Synthetic Medium ◽  
Physiological Role ◽  
Intermolecular Electron Transfer ◽  
Coenzyme Specificity ◽  
Content Type ◽  
Cell Extracts ◽  
N Source ◽  
Chromohalobacter Salexigens

ABSTRACT Chromohalobacter salexigens DSM 3043 can grow on N,N-dimethylglycine (DMG) as the sole C, N, and energy source and utilize sarcosine as the sole N source under aerobic conditions. However, little is known about the genes and enzymes involved in the conversion of DMG to sarcosine in this strain. In the present study, gene disruption and complementation assays indicated that the csal_0990, csal_0991, csal_0992, and csal_0993 genes are responsible for DMG degradation to sarcosine. The csal_0990 gene heterologously expressed in Escherichia coli was proven to encode an unusual DMG dehydrogenase (DMGDH). The enzyme, existing as a monomer of 79 kDa with a noncovalently bound flavin adenine dinucleotide, utilized both DMG and sarcosine as substrates and exhibited dual coenzyme specificity, preferring NAD+ to NADP+. The optimum pH and temperature of enzyme activity were determined to be 7.0 and 60°C, respectively. Kinetic parameters of the enzyme toward its substrates were determined accordingly. Under high-salinity conditions, the presence of DMG inhibited growth of the wild type and induced the production and accumulation of trehalose and glucosylglycerate intracellularly. Moreover, exogenous addition of DMG significantly improved the growth rates of the four DMG– mutants (Δcsal_0990, Δcsal_0991, Δcsal_0992, and Δcsal_0993) incubated at 37°C in S-M63 synthetic medium with sarcosine as the sole N source. 13C nuclear magnetic resonance (13C-NMR) experiments revealed that not only ectoine, glutamate, and N-acetyl-2,4-diaminobutyrate but also glycine betaine (GB), DMG, sarcosine, trehalose, and glucosylglycerate are accumulated intracellularly in the four mutants. IMPORTANCE Although N,N-dimethylglycine (DMG) dehydrogenase (DMGDH) activity was detected in cell extracts of microorganisms, the genes encoding microbial DMGDHs have not been determined until now. In addition, to our knowledge, the physiological role of DMG in moderate halophiles has never been investigated. In this study, we identified the genes involved in DMG degradation to sarcosine, characterized an unusual DMGDH, and investigated the role of DMG in Chromohalobacter salexigens DSM 3043 and its mutants. Our results suggested that the conversion of DMG to sarcosine is accompanied by intramolecular delivery of electrons in DMGDH and intermolecular electron transfer between DMGDH and other electron acceptors. Moreover, an unidentified methyltransferase catalyzing the production of glycine betaine (GB) from DMG but sharing no homology with the reported sarcosine DMG methyltransferases was predicted to be present in the cells. The results of this study expand our understanding of the physiological role of DMG and its catabolism to sarcosine in C. salexigens.

scholarly journals Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida

2017 ◽  
Vol 83 (7) ◽  
Author(s):  
Klara Bojanovič ◽  
Isotta D'Arrigo ◽  
Katherine S. Long
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Pseudomonas Putida ◽  
Cellular Response ◽  
Functional Characterization ◽  
Transcriptional Response ◽  
Stress Conditions ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Content Type

ABSTRACTBacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response ofPseudomonas putidaKT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification of differentially expressed mRNAs and small RNAs (sRNAs). A total of 440 sRNA transcripts were detected, of which 10% correspond to previously annotated sRNAs, 40% to novel intergenic transcripts, and 50% to novel transcripts antisense to annotated genes. Each stress elicits a unique response as far as the extent and dynamics of the transcriptional changes. Nearly 200 protein-encoding genes exhibited significant changes in all stress types, implicating their participation in a general stress response. Almost half of the sRNA transcripts were differentially expressed under at least one condition, suggesting possible functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through whichP. putidaresponds to different stress conditions and increases understanding of bacterial adaptation in natural and industrial settings.IMPORTANCEThis study maps the complete transcriptional response ofP. putidaKT2440 to osmotic, oxidative, and imipenem stress conditions at short and long exposure times. Over 400 sRNA transcripts, consisting of both intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous knowledge of stress response mechanisms due to the depth of the RNA sequencing data. Almost half of the sRNAs exhibit significant expression changes under at least one condition, suggesting their involvement in adaptation to stress conditions and identifying interesting candidates for further functional characterization.

scholarly journals Novel Toxin-Antitoxin Module SlvT-SlvA Regulates Megaplasmid Stability and Incites Solvent Tolerance in Pseudomonas putida S12

2020 ◽  
Vol 86 (13) ◽  
Author(s):  
Hadiastri Kusumawardhani ◽  
David van Dijk ◽  
Rohola Hosseini ◽  
Johannes H. de Winde
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Putida ◽  
Aromatic Compounds ◽  
Efflux Pump ◽  
Gene Clusters ◽  
Host Cells ◽  
Solvent Tolerance ◽  
Content Type ◽  
Solvent Tolerant

ABSTRACT Pseudomonas putida S12 is highly tolerant of organic solvents in saturating concentrations, rendering this microorganism suitable for the industrial production of various aromatic compounds. Previous studies revealed that P. putida S12 contains the single-copy 583-kbp megaplasmid pTTS12. pTTS12 carries several important operons and gene clusters facilitating P. putida S12 survival and growth in the presence of toxic compounds or other environmental stresses. We wished to revisit and further scrutinize the role of pTTS12 in conferring solvent tolerance. To this end, we cured the megaplasmid from P. putida S12 and conclusively confirmed that the SrpABC efflux pump is the major determinant of solvent tolerance on the megaplasmid pTTS12. In addition, we identified a novel toxin-antitoxin module (proposed gene names slvT and slvA, respectively) encoded on pTTS12 which contributes to the solvent tolerance phenotype and is important for conferring stability to the megaplasmid. Chromosomal introduction of the srp operon in combination with the slvAT gene pair created a solvent tolerance phenotype in non-solvent-tolerant strains, such as P. putida KT2440, Escherichia coli TG1, and E. coli BL21(DE3). IMPORTANCE Sustainable alternatives for high-value chemicals can be achieved by using renewable feedstocks in bacterial biocatalysis. However, during the bioproduction of such chemicals and biopolymers, aromatic compounds that function as products, substrates, or intermediates in the production process may exert toxicity to microbial host cells and limit the production yield. Therefore, solvent tolerance is a highly preferable trait for microbial hosts in the biobased production of aromatic chemicals and biopolymers. In this study, we revisit the essential role of megaplasmid pTTS12 from solvent-tolerant Pseudomonas putida S12 for molecular adaptation to an organic solvent. In addition to the solvent extrusion pump (SrpABC), we identified a novel toxin-antitoxin module (SlvAT) which contributes to short-term tolerance in moderate solvent concentrations, as well as to the stability of pTTS12. These two gene clusters were successfully expressed in non-solvent-tolerant strains of P. putida and Escherichia coli strains to confer and enhance solvent tolerance.

scholarly journals Stress Response Protein BolA Influences Fitness and PromotesSalmonella entericaSerovar Typhimurium Virulence

2018 ◽  
Vol 84 (8) ◽  
pp. e02850-17 ◽  
Author(s):  
Dalila Mil-Homens ◽  
Susana Barahona ◽  
Ricardo N. Moreira ◽  
Inês J. Silva ◽  
Sandra N. Pinto ◽  
...  
Keyword(s):  
Host Defense ◽  
Defense Mechanisms ◽  
Cellular Response ◽  
Critical Role ◽  
Bacterial Virulence ◽  
Public Health Care ◽  
Infection Model ◽  
Content Type ◽  
Determining Factor

ABSTRACTThe intracellular pathogenSalmonella entericaserovar Typhimurium has emerged as a major cause of foodborne illness, representing a severe clinical and economic concern worldwide. The capacity of this pathogen to efficiently infect and survive inside the host depends on its ability to synchronize a complex network of virulence mechanisms. Therefore, the identification of new virulence determinants has become of paramount importance in the search of new targets for drug development. BolA-like proteins are widely conserved in all kingdoms of life. InEscherichia coli, this transcription factor has a critical regulatory role in several mechanisms that are tightly related to bacterial virulence. Therefore, in the present work we used the well-established infection modelGalleria mellonellato evaluate the role of BolA protein inS. Typhimurium virulence. We have shown that BolA is an important player inS. Typhimurium pathogenesis. Specifically, the absence of BolA leads to a defective virulence capacity that is most likely related to the remarkable effect of this protein onS. Typhimurium evasion of the cellular response. Furthermore, it was demonstrated that BolA has a critical role in bacterial survival under harsh conditions since BolA conferred protection against acidic and oxidative stress. Hence, we provide evidence that BolA is a determining factor in the ability ofSalmonellato survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence.IMPORTANCEBolA has been described as an important protein for survival in the late stages of bacterial growth and under harsh environmental conditions. High levels of BolA in stationary phase and under stresses have been connected with a plethora of phenotypes, strongly suggesting its important role as a master regulator. Here, we show that BolA is a determining factor in the ability ofSalmonellato survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence. This work constitutes a relevant step toward an understanding of the role of BolA protein and may have an important impact on future studies in other organisms. Therefore, this study is of utmost importance for understanding the genetic and molecular bases involved in the regulation ofSalmonellavirulence and may contribute to future industrial and public health care applications.

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