Characterization and Expression of HmuR, a TonB-Dependent Hemoglobin Receptor of
            <i>Porphyromonas gingivalis</i>

Simpson, William A.; Olczak, Teresa; Genco, Caroline Attardo

doi:10.1128/jb.182.20.5737-5748.2000

Cited by 129 publications

(192 citation statements)

References 44 publications

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“…1c, underlined sequence) than its previously reported variants (Karunakaran et al, 1997;Simpson et al, 2000). Also, the originally described HmuY led to incorrect annotation of the hmuY gene on the genome of P. gingivalis W83 at both Oralgen (http://www.oralgen.…”

Section: Analysis Of Hmuyrstuv Indicates That It Is a Novel Haemin-upmentioning

confidence: 96%

“…The two genes were independently transcribed, and while hemR was repressed by haemin, orf1 was upregulated in the presence of haemin. Using a different P. gingivalis strain, A7436, Simpson et al (2000) demonstrated the presence of a homologue of this locus consisting of hmuY (99 % identical to orf1) and hmuR (identical at the 59 end to hemR but differing significantly at the 39 end). hmuY and hmuR are co-transcribed and repressed by iron.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional organization, regulation and role of the Porphyromonas gingivalis W83 hmu haemin-uptake locus

et al. 2006

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Porphyromonas gingivalis, an oral bacterium associated with periodontal disease, requires haemin for growth. Although several multigenic clusters encoding haemin-uptake systems are present on the genome of P. gingivalis, little is known regarding their transcriptional organization and expression. This study identified a 23 kDa iron-regulated haemin-binding protein encoded by a larger than previously reported variant of hmuY. It was shown that the hmu locus is larger than previously reported and is composed of six genes, hmuYRSTUV, encoding a novel hybrid haemin-uptake system. The locus has an operonic organization and the transcriptional start site is located 292 bp upstream of hmuY. The data indicate that the regulation of the operon is iron-dependent. Interestingly, differential regulation within the operon was demonstrated, resulting in excess of the hmuYR message encoding the outer-membrane proteins when compared to the full-length transcript. In addition, the hmuY transcript is more prevalent than the hmuR transcript. Secondary structure analysis of the hmuYRSTUV mRNA predicted the formation of several potential stem-loops in the 59 ends of hmuR-and hmuS-specific mRNAs, consistent with the differential regulation observed. Finally, it was demonstrated that haemin binding and uptake are elevated in iron-depleted conditions and are reduced 45 % and 70 %, respectively, in an hmu-deficient strain when compared to the parental strain, indicating that the hmu locus plays a major role in haemin acquisition in P. gingivalis. Since homologues of the hmu locus were also found in Bacteroides fragilis, Bacteroides thetaiotaomicron and Prevotella intermedia, these findings may have implications for a better understanding of haemin acquisition in those organisms as well.

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Section: Analysis Of Hmuyrstuv Indicates That It Is a Novel Haemin-upmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Transcriptional organization, regulation and role of the Porphyromonas gingivalis W83 hmu haemin-uptake locus

et al. 2006

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“…Examples include hmuR and feoB-1 and -2. The hmuR (PG1552) gene encodes a TonBdependent outer membrane haemin utilization transporter, which is known to be regulated by iron levels and which possesses a Fur (ferric uptake regulator; PG0465) binding site in its promoter region (Simpson et al, 2000). The feoB-1 (PG1043) gene encodes an inner membrane ferrous iron uptake protein that is essential for pathogenesis of P. gingivalis and is also thought to be Fur-dependent (Dashper et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Identification of bistable populations of Porphyromonas gingivalis that differ in epithelial cell invasion

et al. 2010

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Bistable populations of bacteria give rise to two or more subtypes that exhibit different phenotypes. We have explored whether the periodontal pathogen Porphyromonas gingivalis exhibits bistable invasive phenotypes. Using a modified cell invasion assay, we show for the first time that there are two distinct subtypes within a population of P. gingivalis strains NCTC 11834 and W50 that display differences in their ability to invade oral epithelial cells. The highly invasive subtype invades cells at 10-30-fold higher levels than the poorly invasive subtype and remains highly invasive for approximately 12-16 generations. Analysis of the gingipain activity of these subtypes revealed that the highly invasive type had reduced cell-associated arginine-specific protease activity. The role of Arg-gingipain activity in invasion was verified by enhancement of invasion by rgpAB mutations and by inclusion of an Arg-gingipain inhibitor in invasion assays using wild-type bacteria. In addition, a population of DrgpAB bacteria did not contain a hyperinvasive subtype. Screening of the protease activity of wild-type populations of both strains identified high and low protease subtypes which also showed a corresponding reduction or enhancement, respectively, of invasive capabilities. Microarray analysis of these bistable populations revealed a putative signature set of genes that includes oxidative stress resistance and iron transport genes, and which might be critical to invasion of or survival within epithelial cells.

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“…The molecular mechanisms underlying iron uptake have been extensively studied (Olczak et al, 2005). Genes involved in iron acquisition include the hmuYRSTUV locus (PG1551-PG1556), which encodes a novel hybrid haemin-uptake system (Brunner et al, 2010;Lewis et al, 2006;Olczak et al, 2005Olczak et al, , 2008Simpson et al, 2000Simpson et al, , 2004Smalley et al, 2011); the hbp35 gene (PG0616), which encodes a haemin-binding protein that also exhibits thioredoxin activity (Hiratsuka et al, 2010;Shoji et al, 2010); the surface protein HusA (PG2227), which acts as a haemophore with very high affinity (Gao et al, 2010); the tlr (PG0644) iron transport locus Slakeski et al, 2000); the haemin-binding protein FetB (PG0669) and the surrounding genes in that locus; and PG0465, the ferric uptake regulator (fur) (Olczak et al, 2005). In addition, regulatory mechanisms controlling expression of iron acquisition genes have been identified, including the transcriptional activator encoded by PG1237, which has been shown to control expression of the hmu locus (Wu et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

The nucleoid-associated protein HUβ affects global gene expression in Porphyromonas gingivalis

et al. 2013

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HU is a non-sequence-specific DNA-binding protein and one of the most abundant nucleoidassociated proteins in the bacterial cell. Like Escherichia coli, the genome of Porphyromonas gingivalis is predicted to encode both the HUa (PG1258) and the HUb (PG0121) subunit. We have previously reported that PG0121 encodes a non-specific DNA-binding protein and that PG0121 is co-transcribed with the K-antigen capsule synthesis operon. We also reported that deletion of PG0121 resulted in downregulation of capsule operon expression and produced a P. gingivalis strain that is phenotypically deficient in surface polysaccharide production. Here, we show through complementation experiments in an E. coli MG1655 hupAB double mutant strain that PG0121 encodes a functional HU homologue. Microarray and quantitative RT-PCR analysis were used to further investigate global transcriptional regulation by HUb using comparative expression profiling of the PG0121 (HUb) mutant strain to the parent strain, W83. Our analysis determined that expression of genes encoding proteins involved in a variety of biological functions, including iron acquisition, cell division and translation, as well as a number of predicted nucleoid associated proteins were altered in the PG0121 mutant. Phenotypic and quantitative real-time-PCR (qRT-PCR) analyses determined that under iron-limiting growth conditions, cell division and viability were defective in the PG0121 mutant. Collectively, our studies show that PG0121 does indeed encode a functional HU homologue, and HUb has global regulatory functions in P. gingivalis; it affects not only production of capsular polysaccharides but also expression of genes involved in basic functions, such as cell wall synthesis, cell division and iron uptake. INTRODUCTIONPorphyromonas gingivalis is a Gram-negative obligate anaerobe belonging to the family Bacteroidaceae that persists as a natural member of the human oral microbiota. A shift in the microbial community leading to outgrowth of this anaerobe is directly linked to periodontitis, a chronic inflammatory disease that leads to destruction of the tissues supporting the gums and ultimately, exfoliation of the teeth (Choil et al., 1990;Dzink et al., 1988;Grossi et al., 1994;Lamont & Jenkinson, 2000;Moore et al., 1991). This commensal can colonize, invade and multiply within gingival epithelial cells, as well as penetrate into deeper epithelial cell layers, potentially releasing the whole organism and/or virulence factors into the bloodstream (reviewed by Yilmaz, 2008). In addition to its ability to cause disease in the oral cavity, there are data indicating a role in systemic disease, including its ability to invade vascular endothelial cells (Dorn et al., 2000(Dorn et al., , 2002Jandik et al., 2008) and to cause aggregation of platelets (Pham et al., 2002). For many pathogenic bacteria, surface polysaccharides play a key role in immune modulation et al., 1996). HU typically acts as an accessory protein in virtually all types of nucleoprotein-mediated processes (reviewed by...

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Characterization and Expression of HmuR, a TonB-Dependent Hemoglobin Receptor of Porphyromonas gingivalis

Cited by 129 publications

References 44 publications

Transcriptional organization, regulation and role of the Porphyromonas gingivalis W83 hmu haemin-uptake locus

Transcriptional organization, regulation and role of the Porphyromonas gingivalis W83 hmu haemin-uptake locus

Identification of bistable populations of Porphyromonas gingivalis that differ in epithelial cell invasion

The nucleoid-associated protein HUβ affects global gene expression in Porphyromonas gingivalis

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