Alecia N Septer

University of Georgia, Атина, Georgia, United States

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Publications (12)45.23 Total impact

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    ABSTRACT: The Gac/Csr regulatory system is conserved throughout the γ-proteobacteria and controls key pathways in central carbon metabolism, quorum sensing, biofilm formation, and virulence in important plant and animal pathogens. Here we show that elevated intracellular citrate levels in a Vibrio fischeri aconitase mutant correlate with activation of the Gac/Csr cascade and induction of bright luminescence. Spontaneous or directed mutations in the gene encoding citrate synthase reversed the bright luminescence of aconitase mutants, eliminated their citrate accumulation, and reversed their elevated expression of CsrB. Our data elucidate a correlative link between central metabolic and regulatory pathways, and they suggest that the Gac system senses a blockage at the aconitase step of the TCA cycle, either through elevated citrate levels or a secondary metabolic effect of citrate accumulation, and responds by modulating carbon flow and various functions associated with host colonization, including bioluminescence.
    Molecular Microbiology 11/2014; 95(2). DOI:10.1111/mmi.12864 · 4.42 Impact Factor
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    ABSTRACT: We announce the complete genome sequence for Proteus mirabilis strain BB2000, a model system for self recognition. This opportunistic pathogen contains a single, circular chromosome (3,846,754 bp). Comparisons between this genome and that of strain HI4320 reveal genetic variations corresponding to previously unknown physiological and self-recognition differences.
    Genome Announcements 08/2013; 1(5). DOI:10.1128/genomeA.00024-13
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    ABSTRACT: Unlabelled: Swarming colonies of the bacterium Proteus mirabilis are capable of self-recognition and territorial behavior. Swarms of independent P. mirabilis isolates can recognize each other as foreign and establish a visible boundary where they meet; in contrast, genetically identical swarms merge. The ids genes, which encode self-identity proteins, are necessary but not sufficient for this territorial behavior. Here we have identified two new gene clusters: one (idr) encodes rhs-related products, and another (tss) encodes a putative type VI secretion (T6S) apparatus. The Ids and Idr proteins function independently of each other in extracellular transport and in territorial behaviors; however, these self-recognition systems are linked via this type VI secretion system. The T6S system is required for export of select Ids and Idr proteins. Our results provide a mechanistic and physiological basis for the fundamental behaviors of self-recognition and territoriality in a bacterial model system. Importance: Our results support a model in which self-recognition in P. mirabilis is achieved by the combined action of two independent pathways linked by a shared machinery for export of encoded self-recognition elements. These proteins together form a mechanistic network for self-recognition that can serve as a foundation for examining the prevalent biological phenomena of territorial behaviors and self-recognition in a simple, bacterial model system.
    mBio 06/2013; 4(4). DOI:10.1128/mBio.00374-13 · 6.79 Impact Factor
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    Alecia N Septer · Noreen L Lyell · Eric V Stabb
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    ABSTRACT: Bacteria often use pheromones to coordinate group behaviors in specific environments. While high cell density is required for pheromones to achieve stimulatory levels, environmental cues can also influence pheromone accumulation and signaling. For the squid symbiont Vibrio fischeri ES114, bioluminescence requires pheromone-mediated regulation, and this signaling is induced in the host to a greater extent than in culture, even at an equivalent cell density. Our goal is to better understand this environment-specific control over pheromone signaling and bioluminescence. Previous work with V. fischeri MJ1 showed that iron limitation induces luminescence, and we recently found that ES114 encounters a low-iron environment in its host. Here we show that ES114 induces luminescence at lower cell density and achieves brighter luminescence in low-iron media. This iron-dependent effect on luminescence required ferric uptake regulator (Fur), which we propose influences two pheromone signaling master regulators, LitR and LuxR. Genetic and bioinformatic analyses suggested that under low-iron conditions, Fur-mediated repression of litR is relieved, enabling more LitR to perform its established role as an activator of luxR. Interestingly, Fur may similarly control the LitR homolog SmcR of Vibrio vulnificus. These results reveal an intriguing regulatory link between low-iron conditions, which are often encountered in host tissues, and pheromone-dependent master regulators.
    Applied and Environmental Microbiology 01/2013; 79(6). DOI:10.1128/AEM.03079-12 · 3.67 Impact Factor
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    Alecia N Septer · Eric V Stabb
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    ABSTRACT: Bacterial pheromone signaling is often governed both by environmentally responsive regulators and by positive feedback. This regulatory combination has the potential to coordinate a group response among distinct subpopulations that perceive key environmental stimuli differently. We have explored the interplay between an environmentally responsive regulator and pheromone-mediated positive feedback in intercellular signaling by Vibrio fischeri ES114, a bioluminescent bacterium that colonizes the squid Euprymna scolopes. Bioluminescence in ES114 is controlled in part by N-(3-oxohexanoyl)-L-homoserine lactone (3OC6), a pheromone produced by LuxI that together with LuxR activates transcription of the luxICDABEG operon, initiating a positive feedback loop and inducing luminescence. The lux operon is also regulated by environmentally responsive regulators, including the redox-responsive ArcA/ArcB system, which directly represses lux in culture. Here we show that inactivating arcA leads to increased 3OC6 accumulation to initiate positive feedback. In the absence of positive feedback, arcA-mediated control of luminescence was only ∼2-fold, but luxI-dependent positive feedback contributed more than 100 fold to the net induction of luminescence in the arcA mutant. Consistent with this overriding importance of positive feedback, 3OC6 produced by the arcA mutant induced luminescence in nearby wild-type cells, overcoming their ArcA repression of lux. Similarly, we found that artificially inducing ArcA could effectively repress luminescence before, but not after, positive feedback was initiated. Finally, we show that 3OC6 produced by a subpopulation of symbiotic cells can induce luminescence in other cells co-colonizing the host. Our results suggest that even transient loss of ArcA-mediated regulation in a sub-population of cells can induce luminescence in a wider community. Moreover, they indicate that 3OC6 can communicate information about both cell density and the state of ArcA/ArcB.
    PLoS ONE 11/2012; 7(11):e49590. DOI:10.1371/journal.pone.0049590 · 3.23 Impact Factor
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    ABSTRACT: The protein YfeX from Escherichia coli has been proposed to be essential for the process of iron removal from heme by carrying out a dechelation of heme without cleavage of the porphyrin macrocycle. Since this proposed reaction is unique and would represent the first instance of the biological dechelation of heme, we undertook to characterize YfeX. Our data reveal that YfeX effectively decolorizes the dyes alizarin red and Cibacron blue F3GA and has peroxidase activity with pyrogallal but not guiacol. YfeX oxidizes protoporphyrinogen to protoporphyrin in vitro. However, we were unable to detect any dechelation of heme to free porphyrin with purified YfeX or in cellular extracts of E. coli overexpressing YfeX. Additionally, Vibrio fischeri, an organism that can utilize heme as an iron source when grown under iron limitation, is able to grow with heme as the sole source of iron when its YfeX homolog is absent. Plasmid-driven expression of YfeX in V. fischeri grown with heme did not result in accumulation of protoporphyrin. We propose that YfeX is a typical dye-decolorizing peroxidase (or DyP) and not a dechelatase. The protoporphyrin reported to accumulate when YfeX is overexpressed in E. coli likely arises from the intracellular oxidation of endogenously synthesized protoporphyrinogen and not from dechelation of exogenously supplied heme. Bioinformatic analysis of bacterial YfeX homologs does not identify any connection with iron acquisition but does suggest links to anaerobic-growth-related respiratory pathways. Additionally, some genes encoding homologs of YfeX have tight association with genes encoding a bacterial cytoplasmic encapsulating protein.
    mBio 10/2011; 2(6):e00248-11. DOI:10.1128/mBio.00248-11 · 6.79 Impact Factor
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    Alecia N Septer · Yanling Wang · Edward G Ruby · Eric V Stabb · Anne K Dunn
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    ABSTRACT: Although it is accepted that bacteria-colonizing host tissues are commonly faced with iron-limiting conditions and that pathogenic bacteria often utilize iron from host-derived haem-based compounds, the mechanisms of iron acquisition by beneficial symbiotic bacteria are less clear. The bacterium Vibrio fischeri mutualistically colonizes the light organ of the squid Euprymna scolopes. Genome sequence analysis of V. fischeri revealed a putative haem-uptake gene cluster, and through mutant analysis we confirmed this cluster is important for haemin use by V. fischeri in culture. LacZ reporter assays demonstrated Fur-dependent transcriptional regulation of cluster promoter activity in culture. GFP-based reporter assays revealed that gene cluster promoter activity is induced in symbiotic V. fischeri as early as 14 h post inoculation, although colonization assays with the haem uptake mutant suggested an inability to uptake haem does not begin to limit colonization until later stages of the symbiosis. Our data indicate that the squid light organ is a low iron environment and that haem-based sources of iron are used by symbiotic V. fischeri cells. These findings provide important additional information on the availability of iron during symbiotic colonization of E. scolopes by V. fischeri, as well as the role of haem uptake in non-pathogenic host-microbe interactions.
    Environmental Microbiology 08/2011; 13(11):2855-64. DOI:10.1111/j.1462-2920.2011.02558.x · 6.20 Impact Factor
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    ABSTRACT: Vibrio fischeri serves as a valuable model of bacterial bioluminescence, its regulation, and its functional significance. Light output varies more than 10,000-fold in wild-type isolates from different environments, yet dim and bright strains have similar organization of the light-producing lux genes, with the activator-encoding luxR divergently transcribed from luxICDABEG. By comparing the genomes of bright strain MJ11 and the dimmer ES114, we found that the lux region has diverged more than most shared orthologs, including those flanking lux. Divergence was particularly high in the intergenic sequence between luxR and luxI. Analysis of the intergenic lux region from 18 V. fischeri strains revealed that, with one exception, sequence divergence essentially mirrored strain phylogeny but with relatively high substitution rates. The bases conserved among intergenic luxR-luxI sequences included binding sites for known regulators, such as LuxR and ArcA, and bases of unknown significance, including a striking palindromic repeat. By using this collection of diverse luxR-luxI regions, we found that expression of P(luxI)-lacZ but not P(luxR)-lacZ transcriptional reporters correlated with the luminescence output of the strains from which the promoters originated. We also found that exchange of a small stretch of the luxI-luxR intergenic region between two strains largely reversed their relative brightness. Our results show that the luxR-luxI intergenic region contributes significantly to the variable luminescence output among V. fischeri strains isolated from different environments, although other elements of strain backgrounds also contribute. Moreover, the lux system appears to have evolved relatively rapidly, suggesting unknown environment-specific selective pressures.
    Applied and Environmental Microbiology 02/2011; 77(7):2445-57. DOI:10.1128/AEM.02643-10 · 3.67 Impact Factor
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    Alecia N Septer · Jeffrey L Bose · Anne K Dunn · Eric V Stabb
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    ABSTRACT: Vibrio fischeri induces both anaerobic respiration and bioluminescence during symbiotic infection. In many bacteria, the oxygen-sensitive regulator FNR activates anaerobic respiration, and a preliminary study using the light-generating lux genes from V. fischeri MJ1 cloned in Escherichia coli suggested that FNR stimulates bioluminescence. To test for FNR-mediated regulation of bioluminescence and anaerobic respiration in V. fischeri, we generated fnr mutants of V. fischeri strains MJ1 and ES114. In both strains, FNR was required for normal fumarate- and nitrate-dependent respiration. However, contrary to the report in transgenic E. coli, FNR mediated the repression of lux. ArcA represses bioluminescence, and P(arcA)-lacZ reporters showed reduced expression in fnr mutants, suggesting a possible indirect effect of FNR on bioluminescence via arcA. Finally, the fnr mutant of ES114 was not impaired in colonization of its host squid, Euprymna scolopes. This study extends the characterization of FNR to the Vibrionaceae and underscores the importance of studying lux regulation in its native background.
    FEMS Microbiology Letters 02/2010; 306(1):72-81. DOI:10.1111/j.1574-6968.2010.01938.x · 2.12 Impact Factor
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    ABSTRACT: The Salmonella PreA/PreB two-component system (TCS) is an ortholog of the QseBC TCS of Escherichia coli. In both Salmonella and E. coli, this system has been shown to affect motility and virulence in response to quorum-sensing and hormonal signals, and to affect the transcription of the Salmonella enterica serovar Typhimurium (S. Typhimurium) pmrAB operon, which encodes an important virulence-associated TCS. To determine the PreA/PreB regulon in S. Typhimurium, we performed DNA microarrays comparing the wild type strain and various preA and/or preB mutants in the presence of ectopically expressed preA (qseB). These data confirmed our previous findings of the negative effect of PreB on PreA gene regulation and identified candidate PreA-regulated genes. A proportion of the activated loci were previously identified as PmrA-activated genes (yibD, pmrAB, cptA, etc.) or were genes located in the local region around preA, including the preAB operon. The transcriptional units were defined in this local region by RT-PCR, suggesting three PreA activated operons composed of preA-preB, mdaB-ygiN, and ygiW-STM3175. Several putative virulence-related phenotypes were examined for preAB mutants, resulting in the observation of a host cell invasion and slight virulence defect of a preAB mutant. Contrary to previous reports on this TCS, we were unable to show a PreA/PreB-dependent effect of the quorum-sensing signal AI-2 or of epinephrine on S. Typhimurium with regard to bacterial motility. This work further characterizes this unorthadox OmpR/EnvZ class TCS and provides novel candidate regulated genes for further study. This first in-depth study of the PreA/PreB regulatory system phenotypes and regulation suggests significant comparative differences to the reported function of the orthologous QseB/QseC in E. coli.
    BMC Microbiology 03/2009; 9(1):42. DOI:10.1186/1471-2180-9-42 · 2.73 Impact Factor
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    ABSTRACT: The PmrA/PmrB two-component system encoded by the pmrCAB operon regulates the modification of Salmonella enterica serovar Typhimurium lipopolysaccharide leading to polymyxin B resistance. PmrA and PhoP are the only known activators of pmrCAB. A transposon mutagenesis screen for additional regulators of a pmrC::MudJ fusion led to the identification of a two-component system, termed PreA/PreB (pmrCAB regulators A and B), that controls the transcription of the pmrCAB operon in response to unknown signals. The initial observations indicated that insertions in, or a deletion of, the preB sensor, but not the preA response regulator, caused upregulation of pmrCAB. Interestingly, the expression of pmrCAB was not upregulated in a preAB mutant grown in LB broth, implicating PreA in the increased expression of pmrCAB in the preB strain. This was confirmed by overexpression of preA(+) in preAB or preB backgrounds, which resulted in significant upregulation or further upregulation of pmrCAB. No such effect was observed in any tested preB(+) backgrounds. Additionally, an ectopic construct expressing a preA[D51A] allele also failed to upregulate pmrC in any of the pre backgrounds tested, which implies that there is a need for phosphorylation in the activation of the target genes. The observed upregulation of pmrCAB occurred independently of the response regulators PmrA and PhoP. Although a preB mutation led to increased transcription of pmrCAB, this did not result in a measurable effect on polymyxin B resistance. Our genetic data support a model of regulation whereby, in response to unknown signals, the PreB sensor activates PreA, which in turn indirectly upregulates pmrCAB transcription.
    Journal of Bacteriology 02/2006; 188(1):141-9. DOI:10.1128/JB.188.1.141-149.2006 · 2.81 Impact Factor
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    R Tamayo · B Choudhury · A Septer · M Merighi · R Carlson · J S Gunn
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    ABSTRACT: In response to the in vivo environment, the Salmonella enterica serovar Typhimurium lipopolysaccharide (LPS) is modified. These modifications are controlled in part by the two-component regulatory system PmrA-PmrB, with the addition of 4-aminoarabinose (Ara4N) to the lipid A and phosphoethanolamine (pEtN) to the lipid A and core. Here we demonstrate that the PmrA-regulated STM4118 (cptA) gene is necessary for the addition of pEtN to the LPS core. pmrC, a PmrA-regulated gene necessary for the addition of pEtN to lipid A, did not affect core pEtN addition. Although imparting a similar surface charge modification as Ara4N, which greatly affects polymyxin B resistance and murine virulence, neither pmrC nor cptA plays a dramatic role in antimicrobial peptide resistance in vitro or virulence in the mouse model. Therefore, factors other than surface charge/electrostatic interaction contribute to resistance to antimicrobial peptides such as polymyxin B.
    Journal of Bacteriology 06/2005; 187(10):3391-9. DOI:10.1128/JB.187.10.3391-3399.2005 · 2.81 Impact Factor

Publication Stats

217 Citations
45.23 Total Impact Points


  • 2010–2014
    • University of Georgia
      • Department of Microbiology
      Атина, Georgia, United States
  • 2013
    • Harvard University
      • Department of Molecular and Cell Biology
      Cambridge, Massachusetts, United States
  • 2011
    • University of Wisconsin, Madison
      • Department of Medical Microbiology and Immunology
      Mississippi, United States
  • 2005–2009
    • The Ohio State University
      • • Department of Molecular Virology, Immunology and Medical Genetics
      • • Center for Microbial Interface Biology
      Columbus, OH, United States
  • 2006
    • University of Texas Health Science Center at San Antonio
      San Antonio, Texas, United States