Metal uptake in hostâpathogen interactions: role of iron in Porphyromonas gingivalis interactions with host organisms

Lewis, Janina P.

doi:10.1111/j.1600-0757.2009.00329.x

Cited by 78 publications

(77 citation statements)

References 168 publications

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“…It is thought that P. gingivalis growth is dependent on exogenous sources of heme, and several heme acquisition, uptake, and processing loci have been found to be necessary for growth and virulence (11). Limited heme acquisition or processing may lead to lack of sufficient heme to display on the cell surface.…”

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confidence: 99%

Using Tn-seq To Identify Pigmentation-Related Genes of Porphyromonas gingivalis: Characterization of the Role of a Putative Glycosyltransferase

et al. 2017

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Cellular pigmentation is an important virulence factor of the oral pathogen Porphyromonas gingivalis. Pigmentation has been associated with many bacterial functions, including but not limited to colonization, maintaining a local anaerobic environment by binding oxygen molecules, and defense against reactive oxygen species (ROS) produced by immune cells. Pigmentation-associated loci identified to date have involved lipopolysaccharide, fimbriae, and heme acquisition and processing. We utilized a transposon mutant library of P. gingivalis strain ATCC 33277 and screened for pigmentation-defective colonies using massively parallel sequencing of the transposon junctions (Tn-seq) to identify genes involved in pigmentation. Transposon insertions at 235 separate sites, located in 67 genes and 15 intergenic regions, resulted in altered pigmentation: 7 of the genes had previously been shown to be involved in pigmentation, while 75 genes and intergenic regions had not. To further confirm identification, we generated a smaller transposon mutant library in P. gingivalis strain W83 and identified pigment mutations in several of the same loci as those identified in the screen in ATCC 33277 but also eight that were not identified in the ATCC 33277 screen. PGN_0361/ PG_0264, a putative glycosyltransferase gene located between two tRNA synthetase genes and adjacent to a miniature inverted-repeat transposable element, was identified in the Tn-seq screen and then verified through targeted deletion and complementation. Deletion mutations in PGN_0361/PG_0264 glycosyltransferase abolish pigmentation, modulate gingipain protease activity, and alter lipopolysaccharide. The mechanisms of involvement in pigmentation for other loci identified in this study remain to be determined, but our screen provides the most complete survey of genes involved in pigmentation to date. IMPORTANCE P. gingivalis has been implicated in the onset and progression of periodontal disease. One important virulence factor is the bacterium's ability to produce pigment. Using a transposon library, we were able to identify both known and novel genes involved in pigmentation of P. gingivalis. We identified a glycosyltransferase, previously not associated with pigmentation, that is required for pigmentation and determined its mechanism of involvement. A better understanding of the genes involved in pigmentation may lead to new insights into the complex mechanisms involved in this important virulence characteristic and could facilitate development of novel therapeutics.

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Using Tn-seq To Identify Pigmentation-Related Genes of Porphyromonas gingivalis: Characterization of the Role of a Putative Glycosyltransferase

et al. 2017

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“…Previous studies, using proteomic and transcriptomic analyses to identify differentially expressed proteins and genes, showed that expression of 70 proteins and 160 genes was significantly altered when P. gingivalis was grown under hemin-limited conditions compared to excess-hemin conditions (6). Another recent study indicated that at least 3% of the genes in P. gingivalis genome were modulated in response to a change in hemin concentration (11). These differentially expressed genes or proteins were linked to bacterial invasion, iron transport, and an oxidative-stress response.…”

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OxyR Activation in Porphyromonas gingivalis in Response to a Hemin-Limited Environment

Xie

Zheng

2012

Infect Immun

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ABSTRACTPorphyromonas gingivalisis a Gram-negative obligately anaerobic bacterium associated with several forms of periodontal disease, most closely with chronic periodontitis. Previous studies demonstrated that OxyR plays an important role in the aerotolerance ofP. gingivalisby upregulating the expression of oxidative-stress genes. Increases in oxygen tension and in H2O2both induce activation of OxyR. It is also known thatP. gingivalisrequires hemin as an iron source for its growth. In this study, we found that a hemin-limited growth environment significantly enhanced OxyR activity inP. gingivalis. As a result, expression ofsod,dps, andahpCwas also upregulated. Using a chromatin immunoprecipitation quantitative PCR (qPCR) analysis, DNA binding of activated OxyR to the promoter of thesodgene was enhanced inP. gingivalisgrown under hemin-limited conditions compared to excess-hemin conditions. Cellular tolerance of H2O2was also enhanced when hemin was limited in the growth medium ofP. gingivalis. Our work supports a model in which hemin serves as a signal for the regulation of OxyR activity and indicates thatP. gingivaliscoordinately regulates expression of oxidative-stress-related genes by this hemin concentration-dependent pathway.

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“…Since hemin is too large to diffuse freely through the bacterial membranes, P. gingivalis requires transport of hemin across two membranes by a process that requires energy (41). Three multigenic clusters have been detected in the genome of P. gingivalis W83, encoding proteins thought to be involved in hemin uptake (26): IhtABCDE (iron-heme transport), Tlr-htrABCD (hemin uptake), and HmuYRSTUV (hemin uptake).…”

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Antibacterial Action of Polyphosphate on Porphyromonas gingivalis

Moon

Park

Lee

2011

Antimicrob Agents Chemother

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Polyphosphate [poly(P)] has antibacterial activity against various Gram-positive bacteria. In contrast, Gram-negative bacteria are generally resistant to poly(P). Here, we describe the antibacterial characterization of poly(P) against a Gram-negative periodontopathogen, Porphyromonas gingivalis. The MICs of pyrophosphate (Na 4 P 2 O 7 ) and all poly(P) (Na n ؉ 2 P n O 3n ؉ 1 ; n ‫؍‬ 3 to 75) tested for the bacterium by the agar dilution method were 0.24% and 0.06%, respectively. Orthophosphate (Na 2 HPO 4 ) failed to inhibit bacterial growth. Poly-P75 was chosen for further study. In liquid medium, 0.03% poly-P75 was bactericidal against P. gingivalis irrespective of the growth phase and inoculum size, ranging from 10 5 to10 9 cells/ml. UV-visible spectra of the pigments from P. gingivalis grown on blood agar with or without poly-P75 showed that poly-P75 reduced the formation of -oxo bisheme by the bacterium. Poly-P75 increased hemin accumulation on the P. gingivalis surface and decreased energy-driven uptake of hemin by the bacterium. The expression of the genes encoding hemagglutinins, gingipains, hemin uptake loci, chromosome replication, and energy production was downregulated, while that of the genes related to iron storage and oxidative stress was upregulated by poly-P75. The transmission electron microscope showed morphologically atypical cells with electron-dense granules and condensed nucleoid in the cytoplasm. Collectively, poly(P) is bactericidal against P. gingivalis, in which hemin/heme utilization is disturbed and oxidative stress is increased by poly(P).Inorganic polyphosphate [poly(P)] is a ubiquitous compound found in bacteria, fungi, algae, plants, and animals. The poly(P) found in the organisms is a chain of a few or many hundreds of phosphate (P i ) residues linked by high-energy phosphoanhydride. It performs varied functions in bacteria: it can serve as an ATP source and substitute, it is a strong chelator of metal ions and thus can regulate the levels of the ions in the cells, it is a channel for DNA entry, and it is a regulator that contributes to bacterial resistance and survival under stress and stringent conditions (18). Therefore, intracellular poly(P) is considered a virulence factor of microorganisms.In contrast, exogenous poly(P) has attracted considerable attention as an antimicrobial agent, since it can prevent spoilage of food (29, 32), and it is listed as a GRAS (generally recognized as safe) food additive by the FDA. Poly(P) inhibits the growth of various Gram-positive bacteria, such as Staphylococcus aureus (14,17,22,35,52), Listeria monocytogenes (37, 52), Sarcina lutea (35), Bacillus cereus, and Lactobacillus, and of fungi, such as Aspergillus flavus (17,28). Concerning oral bacteria, mutans streptococci were first found to be inhibited by condensed phosphate, resulting in a decrease of plaque formation and dental caries (5, 39). The ability of poly(P) to chelate divalent cations is regarded as relevant to the antibacterial effects of poly(P), contributing to cell division i...

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Metal uptake in hostâpathogen interactions: role of iron in Porphyromonas gingivalis interactions with host organisms

Cited by 78 publications

References 168 publications

Using Tn-seq To Identify Pigmentation-Related Genes of Porphyromonas gingivalis: Characterization of the Role of a Putative Glycosyltransferase

Using Tn-seq To Identify Pigmentation-Related Genes of Porphyromonas gingivalis: Characterization of the Role of a Putative Glycosyltransferase

OxyR Activation in Porphyromonas gingivalis in Response to a Hemin-Limited Environment

Antibacterial Action of Polyphosphate on Porphyromonas gingivalis

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Metal uptake in hostâpathogen interactions: role of iron in Porphyromonas gingivalis interactions with host organisms

Cited by 78 publications

References 168 publications

Using Tn-seq To Identify Pigmentation-Related Genes of Porphyromonas gingivalis: Characterization of the Role of a Putative Glycosyltransferase

Using Tn-seq To Identify Pigmentation-Related Genes of Porphyromonas gingivalis: Characterization of the Role of a Putative Glycosyltransferase

OxyR Activation in Porphyromonas gingivalis in Response to a Hemin-Limited Environment

Antibacterial Action of Polyphosphate on Porphyromonas gingivalis

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Metal uptake in hostâpathogen interactions: role of iron in Porphyromonas gingivalis interactions with host organisms