scholarly journals The Irr and RirA Proteins Participate in a Complex Regulatory Circuit and Act in Concert To Modulate Bacterioferritin Expression in Ensifer meliloti 1021

2017 ◽  
Vol 83 (16) ◽  
Author(s):  
Daniela Costa ◽  
Vanesa Amarelle ◽  
Claudio Valverde ◽  
Mark R. O'Brian ◽  
Elena Fabiano
Keyword(s):  
Gene Expression ◽  
Small Rna ◽  
Iron Homeostasis ◽  
Sufficient Conditions ◽  
Iron Storage ◽  
Content Type ◽  
Reading Frame ◽  
Regulatory Circuit ◽  
Ensifer Meliloti ◽  
Rhizobial Species

ABSTRACT In this work we found that the bfr gene of the rhizobial species Ensifer meliloti, encoding a bacterioferritin iron storage protein, is involved in iron homeostasis and the oxidative stress response. This gene is located downstream of and overlapping the smc03787 open reading frame (ORF). No well-predicted RirA or Irr boxes were found in the region immediately upstream of the bfr gene although two presumptive RirA boxes and one presumptive Irr box were present in the putative promoter of smc03787. We demonstrate that bfr gene expression is enhanced under iron-sufficient conditions and that Irr and RirA modulate this expression. The pattern of bfr gene expression as well as the response to Irr and RirA is inversely correlated to that of smc03787. Moreover, our results suggest that the small RNA SmelC759 participates in RirA- and Irr-mediated regulation of bfr expression and that additional unknown factors are involved in iron-dependent regulation. IMPORTANCE E. meliloti belongs to the Alphaproteobacteria, a group of bacteria that includes several species able to associate with eukaryotic hosts, from mammals to plants, in a symbiotic or pathogenic manner. Regulation of iron homeostasis in this group of bacteria differs from that found in the well-studied Gammaproteobacteria. In this work we analyzed the effect of rirA and irr mutations on bfr gene expression. We demonstrate the effect of an irr mutation on iron homeostasis in this bacterial genus. Moreover, results obtained indicate a complex regulatory circuit where multiple regulators, including RirA, Irr, the small RNA SmelC759, and still unknown factors, act in concert to balance bfr gene expression.

scholarly journals Regulation of Iron Storage by CsrA Supports Exponential Growth of Escherichia coli

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Christine Pourciau ◽  
Archana Pannuri ◽  
Anastasia Potts ◽  
Helen Yakhnin ◽  
Paul Babitzke ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Escherichia Coli ◽  
Exponential Growth ◽  
Iron Homeostasis ◽  
Iron Storage ◽  
Content Type ◽  
Mrna Targets ◽  
Cellular Iron ◽  
The Impact

ABSTRACT The global regulatory protein CsrA coordinates gene expression in response to physiological cues reflecting cellular stress and nutrition. CsrA binding to the 5′ segments of mRNA targets affects their translation, RNA stability, and/or transcript elongation. Recent studies identified probable mRNA targets of CsrA that are involved in iron uptake and storage in Escherichia coli, suggesting an unexplored role for CsrA in regulating iron homeostasis. Here, we assessed the impact of CsrA on iron-related gene expression, cellular iron, and growth under various iron levels. We investigated five new targets of CsrA regulation, including the genes for 4 ferritin or ferritin-like iron storage proteins (ISPs) and the stress-inducible Fe-S repair protein, SufA. CsrA bound with high affinity and specificity to ftnB, bfr, and dps mRNAs and inhibited their translation, while it modestly activated ftnA expression. Furthermore, CsrA was found to regulate cellular iron levels and support growth by repressing the expression of genes for ISPs, most importantly, ferritin B (FtnB) and bacterioferritin (Bfr). Iron starvation did not substantially affect cellular levels of CsrA or its small RNA (sRNA) antagonists, CsrB and CsrC. csrA disruption led to increased resistance to the lethal effects of H2O2 during exponential growth, consistent with a regulatory role in oxidative stress resistance. We propose that during exponential growth and under minimal stress, CsrA represses the deleterious expression of the ISPs that function under oxidative stress and stationary-phase conditions (FtnB, Bfr, and Dps), thus ensuring that cellular iron is available to processes that are required for growth. IMPORTANCE Iron is an essential micronutrient for nearly all living organisms but is toxic in excess. Consequently, the maintenance of iron homeostasis is a critical biological process, and the genes involved in this function are tightly regulated. Here, we explored a new role for the bacterial RNA binding protein CsrA in the regulation of iron homeostasis. CsrA was shown to be a key regulator of iron storage genes in Escherichia coli, with consequential effects on cellular iron levels and growth. Our findings establish a model in which robust CsrA activity during the exponential phase of growth leads to repression of genes whose products sequester iron or divert it to unnecessary stress response processes. In so doing, CsrA supports E. coli growth under iron-limiting laboratory conditions and may promote fitness in the competitive iron-limited environment of the host large intestine.

scholarly journals Impact of Anaerobiosis on Expression of the Iron-Responsive Fur and RyhB Regulons

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Nicole A. Beauchene ◽  
Kevin S. Myers ◽  
Dongjun Chung ◽  
Dan M. Park ◽  
Allison M. Weisnicht ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Rna ◽  
Iron Homeostasis ◽  
Target Genes ◽  
Arms Race ◽  
Anaerobic Conditions ◽  
Content Type ◽  
Expression Of Genes ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

ABSTRACTIron, a major protein cofactor, is essential for most organisms. Despite the well-known effects of O2on the oxidation state and solubility of iron, the impact of O2on cellular iron homeostasis is not well understood. Here we report that inEscherichia coliK-12, the lack of O2dramatically changes expression of genes controlled by the global regulators of iron homeostasis, the transcription factor Fur and the small RNA RyhB. Using chromatin immunoprecipitation sequencing (ChIP-seq), we found anaerobic conditions promote Fur binding to more locations across the genome. However, by expression profiling, we discovered that the major effect of anaerobiosis was to increase the magnitude of Fur regulation, leading to increased expression of iron storage proteins and decreased expression of most iron uptake pathways and several Mn-binding proteins. This change in the pattern of gene expression also correlated with an unanticipated decrease in Mn in anaerobic cells. Changes in the genes posttranscriptionally regulated by RyhB under aerobic and anaerobic conditions could be attributed to O2-dependent changes in transcription of the target genes: aerobic RyhB targets were enriched in iron-containing proteins associated with aerobic energy metabolism, whereas anaerobic RyhB targets were enriched in iron-containing anaerobic respiratory functions. Overall, these studies showed that anaerobiosis has a larger impact on iron homeostasis than previously anticipated, both by expanding the number of direct Fur target genes and the magnitude of their regulation and by altering the expression of genes predicted to be posttranscriptionally regulated by the small RNA RyhB under iron-limiting conditions.IMPORTANCEMicrobes and host cells engage in an “arms race” for iron, an essential nutrient that is often scarce in the environment. Studies of iron homeostasis have been key to understanding the control of iron acquisition and the downstream pathways that enable microbes to compete for this valuable resource. Here we report that O2availability affects the gene expression programs of twoEscherichia colimaster regulators that function in iron homeostasis: the transcription factor Fur and the small RNA regulator RyhB. Fur appeared to be more active under anaerobic conditions, suggesting a change in the set point for iron homeostasis. RyhB preferentially targeted iron-containing proteins of respiration-linked pathways, which are differentially expressed under aerobic and anaerobic conditions. Such findings may be relevant to the success of bacteria within their hosts since zones of reduced O2may actually reduce bacterial iron demands, making it easier to win the arms race for iron.

scholarly journals Ethanolamine Utilization and Bacterial Microcompartment Formation Are Subject to Carbon Catabolite Repression

2019 ◽  
Vol 201 (10) ◽  
Author(s):  
Karan Gautam Kaval ◽  
Margo Gebbie ◽  
Jonathan R. Goodson ◽  
Melissa R. Cruz ◽  
Wade C. Winkler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enterococcus Faecalis ◽  
Small Rna ◽  
Catabolite Repression ◽  
Carbon Catabolite Repression ◽  
Bioinformatics Analysis ◽  
Maximum Efficiency ◽  
Gi Tract ◽  
Content Type ◽  
Regulatory Factors

ABSTRACT Ethanolamine (EA) is a compound prevalent in the gastrointestinal (GI) tract that can be used as a carbon, nitrogen, and/or energy source. Enterococcus faecalis, a GI commensal and opportunistic pathogen, contains approximately 20 ethanolamine utilization (eut) genes encoding the necessary regulatory, enzymatic, and structural proteins for this process. Here, using a chemically defined medium, two regulatory factors that affect EA utilization were examined. First, the functional consequences of loss of the small RNA (sRNA) EutX on the efficacy of EA utilization were investigated. One effect observed, as loss of this negative regulator causes an increase in eut gene expression, was a concomitant increase in the number of catabolic bacterial microcompartments (BMCs) formed. However, despite this increase, the growth of the strain was repressed, suggesting that the overall efficacy of EA utilization was negatively affected. Second, utilizing a deletion mutant and a complement, carbon catabolite control protein A (CcpA) was shown to be responsible for the repression of EA utilization in the presence of glucose. A predicted cre site in one of the three EA-inducible promoters, PeutS, was identified as the target of CcpA. However, CcpA was shown to affect the activation of all the promoters indirectly through the two-component system EutV and EutW, whose genes are under the control of the PeutS promoter. Moreover, a bioinformatics analysis of bacteria predicted to contain CcpA and cre sites revealed that a preponderance of BMC-containing operons are likely regulated by carbon catabolite repression (CCR). IMPORTANCE Ethanolamine (EA) is a compound commonly found in the gastrointestinal (GI) tract that can affect the behavior of human pathogens that can sense and utilize it, such as Enterococcus faecalis and Salmonella. Therefore, it is important to understand how the genes that govern EA utilization are regulated. In this work, we investigated two regulatory factors that control this process. One factor, a small RNA (sRNA), is shown to be important for generating the right levels of gene expression for maximum efficiency. The second factor, a transcriptional repressor, is important for preventing expression when other preferred sources of energy are available. Furthermore, a global bioinformatics analysis revealed that this second mechanism of transcriptional regulation likely operates on similar genes in related bacteria.

scholarly journals σIfromBacillus subtilis: Impact on Gene Expression and Characterization of σI-Dependent Transcription That Requires New Types of Promoters with Extended −35 and −10 Elements

2018 ◽  
Vol 200 (17) ◽  
Author(s):  
Olga Ramaniuk ◽  
Martin Převorovský ◽  
Jiří Pospíšil ◽  
Dragana Vítovská ◽  
Olga Kofroňová ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Iron Metabolism ◽  
Transcription Initiation ◽  
Iron Homeostasis ◽  
Model Organism ◽  
Content Type ◽  
Σ Factor

ABSTRACTThe σIsigma factor fromBacillus subtilisis a σ factor associated with RNA polymerase (RNAP) that was previously implicated in adaptation of the cell to elevated temperature. Here, we provide a comprehensive characterization of this transcriptional regulator. By transcriptome sequencing (RNA-seq) of wild-type (wt) and σI-null strains at 37°C and 52°C, we identified ∼130 genes affected by the absence of σI. Further analysis revealed that the majority of these genes were affected indirectly by σI. The σIregulon, i.e., the genes directly regulated by σI, consists of 16 genes, of which eight (thedhbandykuoperons) are involved in iron metabolism. The involvement of σIin iron metabolism was confirmed phenotypically. Next, we set up anin vitrotranscription system and defined and experimentally validated the promoter sequence logo that, in addition to −35 and −10 regions, also contains extended −35 and −10 motifs. Thus, σI-dependent promoters are relatively information rich in comparison with most other promoters. In summary, this study supplies information about the least-explored σ factor from the industrially important model organismB. subtilis.IMPORTANCEIn bacteria, σ factors are essential for transcription initiation. Knowledge about their regulons (i.e., genes transcribed from promoters dependent on these σ factors) is the key for understanding how bacteria cope with the changing environment and could be instrumental for biotechnologically motivated rewiring of gene expression. Here, we characterize the σIregulon from the industrially important model Gram-positive bacteriumBacillus subtilis. We reveal that σIaffects expression of ∼130 genes, of which 16 are directly regulated by σI, including genes encoding proteins involved in iron homeostasis. Detailed analysis of promoter elements then identifies unique sequences important for σI-dependent transcription. This study thus provides a comprehensive view on this underexplored component of theB. subtilistranscription machinery.

scholarly journals The Pseudomonas aeruginosa PrrF Small RNAs Regulate Iron Homeostasis during Acute Murine Lung Infection

2017 ◽  
Vol 85 (5) ◽  
Author(s):  
Alexandria A. Reinhart ◽  
Angela T. Nguyen ◽  
Luke K. Brewer ◽  
Justin Bevere ◽  
Jace W. Jones ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Small Rnas ◽  
Iron Homeostasis ◽  
Critical Role ◽  
Opportunistic Pathogen ◽  
Lung Infection ◽  
Content Type ◽  
The Individual

ABSTRACT Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that requires iron for virulence. Iron homeostasis is maintained in part by the PrrF1 and PrrF2 small RNAs (sRNAs), which block the expression of iron-containing proteins under iron-depleted conditions. The PrrF sRNAs also promote the production of the Pseudomonas quinolone signal (PQS), a quorum sensing molecule that activates the expression of several virulence genes. The tandem arrangement of the prrF genes allows for expression of a third sRNA, PrrH, which is predicted to regulate gene expression through its unique sequence derived from the prrF1-prrF2 intergenic (IG) sequence (the PrrHIG sequence). Previous studies showed that the prrF locus is required for acute lung infection. However, the individual functions of the PrrF and PrrH sRNAs were not determined. Here, we describe a system for differentiating PrrF and PrrH functions by deleting the PrrHIG sequence [prrF(ΔHIG)]. Our analyses of this construct indicate that the PrrF sRNAs, but not PrrH, are required for acute lung infection by P. aeruginosa. Moreover, we show that the virulence defect of the ΔprrF1-prrF2 mutant is due to decreased bacterial burden during acute lung infection. In vivo analysis of gene expression in lung homogenates shows that PrrF-mediated regulation of genes for iron-containing proteins is disrupted in the ΔprrF1-prrF2 mutant during infection, while the expression of genes that mediate PrrF-regulated PQS production are not affected by prrF deletion in vivo. Combined, these studies demonstrate that regulation of iron utilization plays a critical role in P. aeruginosa's ability to survive during infection.

scholarly journals Cell Envelope Perturbation Induces Oxidative Stress and Changes in Iron Homeostasis in Vibrio cholerae

2009 ◽  
Vol 191 (17) ◽  
pp. 5398-5408 ◽  
Author(s):  
Aleksandra E. Sikora ◽  
Sinem Beyhan ◽  
Michael Bagdasarian ◽  
Fitnat H. Yildiz ◽  
Maria Sandkvist
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Outer Membrane ◽  
Vibrio Cholerae ◽  
Iron Homeostasis ◽  
Cell Envelope ◽  
Membrane Integrity ◽  
Genetic Alterations ◽  
Iron Storage ◽  
Study Gene Expression

ABSTRACT The Vibrio cholerae type II secretion (T2S) machinery is a multiprotein complex that spans the cell envelope. When the T2S system is inactivated, cholera toxin and other exoproteins accumulate in the periplasmic compartment. Additionally, loss of secretion via the T2S system leads to a reduced growth rate, compromised outer membrane integrity, and induction of the extracytoplasmic stress factor RpoE (A. E. Sikora, S. R. Lybarger, and M. Sandkvist, J. Bacteriol. 189:8484-8495, 2007). In this study, gene expression profiling reveals that inactivation of the T2S system alters the expression of genes encoding cell envelope components and proteins involved in central metabolism, chemotaxis, motility, oxidative stress, and iron storage and acquisition. Consistent with the gene expression data, molecular and biochemical analyses indicate that the T2S mutants suffer from internal oxidative stress and increased levels of intracellular ferrous iron. By using a tolA mutant of V. cholerae that shares a similar compromised membrane phenotype but maintains a functional T2S machinery, we show that the formation of radical oxygen species, induction of oxidative stress, and changes in iron physiology are likely general responses to cell envelope damage and are not unique to T2S mutants. Finally, we demonstrate that disruption of the V. cholerae cell envelope by chemical treatment with polymyxin B similarly results in induction of the RpoE-mediated stress response, increased sensitivity to oxidants, and a change in iron metabolism. We propose that many types of extracytoplasmic stresses, caused either by genetic alterations of outer membrane constituents or by chemical or physical damage to the cell envelope, induce common signaling pathways that ultimately lead to internal oxidative stress and misregulation of iron homeostasis.

scholarly journals Mitochondria InfluenceCDR1Efflux Pump Activity, Hog1-Mediated Oxidative Stress Pathway, Iron Homeostasis, and Ergosterol Levels in Candida albicans

2013 ◽  
Vol 57 (11) ◽  
pp. 5580-5599 ◽  
Author(s):  
Edwina Thomas ◽  
Elvira Roman ◽  
Steven Claypool ◽  
Nikhat Manzoor ◽  
Jesús Pla ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Cellular Response ◽  
Iron Homeostasis ◽  
Sufficient Conditions ◽  
Ergosterol Biosynthesis ◽  
Biosynthesis Pathway ◽  
Content Type ◽  
Iron Assimilation ◽  
Increased Susceptibility

ABSTRACTMitochondrial dysfunction inCandida albicansis known to be associated with drug susceptibility, cell wall integrity, phospholipid homeostasis, and virulence. In this study, we deletedCaFZO1, a key component required during biogenesis of functional mitochondria. Cells withFZO1deleted displayed fragmented mitochondria, mitochondrial genome loss, and reduced mitochondrial membrane potential and were rendered sensitive to azoles and peroxide. In order to understand the cellular response to dysfunctional mitochondria, genome-wide expression profiling offzo1Δ/Δ cells was performed. Our results show that the increased susceptibility to azoles was likely due to reduced efflux activity ofCDRefflux pumps, caused by the missorting of Cdr1p into the vacuole. In addition,fzo1Δ/Δ cells showed upregulation of genes involved in iron assimilation, in iron-sufficient conditions, characteristic of iron-starved cells. One of the consequent effects was downregulation of genes of the ergosterol biosynthesis pathway with a commensurate decrease in cellular ergosterol levels. We therefore connect deregulated iron metabolism to ergosterol biosynthesis pathway in response to dysfunctional mitochondria. Impaired activation of the Hog1 pathway in the mutant was the basis for increased susceptibility to peroxide and increase in reactive oxygen species, indicating the importance of functional mitochondria in controlling Hog1-mediated oxidative stress response. Mitochondrial phospholipid levels were also altered as indicated by an increase in phosphatidylserine and phosphatidylethanolamine and decrease in phosphatidylcholine infzo1Δ/Δ cells. Collectively, these findings reinforce the connection between functional mitochondria and azole tolerance, oxidant-mediated stress, and iron homeostasis inC. albicans.

scholarly journals A Membrane-Embedded Amino Acid Couples the SpoIIQ Channel Protein to Anti-Sigma Factor Transcriptional Repression during Bacillus subtilis Sporulation

2016 ◽  
Vol 198 (9) ◽  
pp. 1451-1463 ◽  
Author(s):  
Kelly A. Flanagan ◽  
Joseph D. Comber ◽  
Elizabeth Mearls ◽  
Colleen Fenton ◽  
Anna F. Wang Erickson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Amino Acid ◽  
Sigma Factor ◽  
Late Gene ◽  
Late Gene Expression ◽  
Gene Encoding ◽  
Content Type ◽  
Regulatory Circuit ◽  
Gene Regulatory

ABSTRACTSpoIIQ is an essential component of a channel connecting the developing forespore to the adjacent mother cell duringBacillus subtilissporulation. This channel is generally required for late gene expression in the forespore, including that directed by the late-acting sigma factor σG. Here, we present evidence that SpoIIQ also participates in a previously unknown gene regulatory circuit that specifically represses expression of the gene encoding the anti-sigma factor CsfB, a potent inhibitor of σG. ThecsfBgene is ordinarily transcribed in the forespore only by the early-acting sigma factor σF. However, in a mutant lacking the highly conserved SpoIIQ transmembrane amino acid Tyr-28,csfBwas also aberrantly transcribed later by σG, the very target of CsfB inhibition. This regulation ofcsfBby SpoIIQ Tyr-28 is specific, given that the expression of other σF-dependent genes was unaffected. Moreover, we identified a conserved element within thecsfBpromoter region that is both necessary and sufficient for SpoIIQ Tyr-28-mediated inhibition. These results indicate that SpoIIQ is a bifunctional protein that not only generally promotes σGactivity in the forespore as a channel component but also specifically maximizes σGactivity as part of a gene regulatory circuit that represses σG-dependent expression of its own inhibitor, CsfB. Finally, we demonstrate that SpoIIQ Tyr-28 is required for the proper localization and stability of the SpoIIE phosphatase, raising the possibility that these two multifunctional proteins cooperate to fine-tune developmental gene expression in the forespore at late times.IMPORTANCECellular development is orchestrated by gene regulatory networks that activate or repress developmental genes at the right time and place. Late gene expression in the developingBacillus subtilisspore is directed by the alternative sigma factor σG. The activity of σGrequires a channel apparatus through which the adjacent mother cell provides substrates that generally support gene expression. Here we report that the channel protein SpoIIQ also specifically maximizes σGactivity as part of a previously unknown regulatory circuit that prevents σGfrom activating transcription of the gene encoding its own inhibitor, the anti-sigma factor CsfB. The discovery of this regulatory circuit significantly expands our understanding of the gene regulatory network controlling late gene expression in the developingB. subtilisspore.

scholarly journals The Sinorhizobium meliloti SyrM Regulon: Effects on Global Gene Expression Are Mediated bysyrAandnodD3

2015 ◽  
Vol 197 (10) ◽  
pp. 1792-1806 ◽  
Author(s):  
Melanie J. Barnett ◽  
Sharon R. Long
Keyword(s):  
Gene Expression ◽  
Sinorhizobium Meliloti ◽  
Developmental Process ◽  
Global Gene Expression ◽  
Subsequent Increase ◽  
Altered Expression ◽  
Content Type ◽  
Regulatory Circuit ◽  
Regulatory Circuits ◽  
Exogenous Compounds

ABSTRACTInSinorhizobium meliloti, three NodD transcriptional regulators activate bacterial nodulation (nod) gene expression. NodD1 and NodD2 require plant compounds to activatenodgenes. The NodD3 protein does not require exogenous compounds to activatenodgene expression; instead, another transcriptional regulator, SyrM, activatesnodD3expression. In addition, NodD3 can activatesyrMexpression. SyrM also activates expression of another gene,syrA, which when overexpressed causes a dramatic increase in exopolysaccharide production. In a previous study, we identified more than 200 genes with altered expression in a strain overexpressingnodD3. In this work, we define the transcriptomes of strains overexpressingsyrMorsyrA. ThesyrM,nodD3, andsyrAoverexpression transcriptomes share similar gene expression changes; analyses imply thatnodD3andsyrAare the only targets directly activated by SyrM. We propose that most of the gene expression changes observed whennodD3is overexpressed are due to NodD3 activation ofsyrMexpression, which in turn stimulates SyrM activation ofsyrAexpression. The subsequent increase in SyrA abundance results in broad changes in gene expression, most likely mediated by the ChvI-ExoS-ExoR regulatory circuit.IMPORTANCESymbioses with bacteria are prevalent across the animal and plant kingdoms. Our system of study, the rhizobium-legume symbiosis (Sinorhizobium melilotiandMedicagospp.), involves specific host-microbe signaling, differentiation in both partners, and metabolic exchange of bacterial fixed nitrogen for host photosynthate. During this complex developmental process, both bacteria and plants undergo profound changes in gene expression. TheS. melilotiSyrM-NodD3-SyrA and ChvI-ExoS-ExoR regulatory circuits affect gene expression and are important for optimal symbiosis. In this study, we defined the transcriptomes ofS. melilotioverexpressing SyrM or SyrA. In addition to identifying new targets of the SyrM-NodD3-SyrA regulatory circuit, our work further suggests how it is linked to the ChvI-ExoS-ExoR regulatory circuit.

scholarly journals Ferric Uptake Regulator and Its Role in the Pathogenesis of Nontypeable Haemophilus influenzae

2013 ◽  
Vol 81 (4) ◽  
pp. 1221-1233 ◽  
Author(s):  
Alistair Harrison ◽  
Estevan A. Santana ◽  
Blake R. Szelestey ◽  
David E. Newsom ◽  
Peter White ◽  
...  
Keyword(s):  
Gene Expression ◽  
Haemophilus Influenzae ◽  
Iron Homeostasis ◽  
Expression Patterns ◽  
Opportunistic Pathogen ◽  
Nontypeable Haemophilus Influenzae ◽  
Bacterial Persistence ◽  
Content Type ◽  
Regulatory Pathways ◽  
Iron Utilization

ABSTRACTNontypeableHaemophilus influenzae(NTHi) is a commensal microorganism of the human nasopharynx, and yet is also an opportunistic pathogen of the upper and lower respiratory tracts. Host microenvironments influence gene expression patterns, likely critical for NTHi persistence. The host sequesters iron as a mechanism to control microbial growth, and yet iron limitation influences gene expression and subsequent production of proteins involved in iron homeostasis. Careful regulation of iron uptake, via theferricuptakeregulator Fur, is essential in multiple bacteria, including NTHi. We hypothesized therefore that Fur contributes to iron homeostasis in NTHi, is critical for bacterial persistence, and likely regulates expression of virulence factors. Toward this end,furwas deleted in the prototypic NTHi clinical isolate, 86-028NP, and we assessed gene expression regulated by Fur. As expected, expression of the majority of genes that encode proteins with predicted roles in iron utilization was repressed by Fur. However, 14 Fur-regulated genes encode proteins with no known function, and yet may contribute to iron utilization or other biological functions. In a mammalian model of human otitis media, we determined that Fur was critical for bacterial persistence, indicating an important role for Fur-mediated iron homeostasis in disease progression. These data provide a profile of genes regulated by Fur in NTHi and likely identify additional regulatory pathways involved in iron utilization. Identification of such pathways will increase our understanding of how this pathogen can persist within host microenvironments, as a common commensal and, importantly, as a pathogen with significant clinical impact.

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