Roles of porphyrins and host iron transport proteins in regulation of growth of Porphyromonas gingivalis W50

Bramanti, Thomas E.; Holt, Stanley C.

doi:10.1128/jb.173.22.7330-7339.1991

Cited by 128 publications

(160 citation statements)

References 54 publications

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“…Our studies were done in Mycoplasma broth containing low levels of iron and thus the 10 mM DP that we used was sufficient to chelate the free iron present in the medium, as demonstrated by previous work (Bramanti & Holt, 1991;Dashper et al, 2004). In addition, previous studies demonstrated haemin-dependent regulation.…”

Section: Discussionmentioning

confidence: 97%

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: Discussionmentioning

confidence: 97%

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

et al. 2006

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“…P. gingivalis cannot synthesize the protoporhyrin IX ring and does not have siderophores for alternative bioavailability of hemin [36–39]. Therefore, P. gingivalis depends on the host for a supply of heme [40].…”

Section: The Lipid a Structure Is Modulated By Hemin And Temperaturementioning

confidence: 99%

Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signalling

Olsen

Singhrao

2018

Journal of Oral Microbiology

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Lipopolysaccharide (LPS) of Porphyromonas gingivalis exists in at least two known forms, O-LPS and A-LPS. A-LPS shows heterogeneity in which two isoforms designated LPS1,435/1,449 and LPS1,690 appear responsible for tissue-specific immune signalling pathways activation and increased virulence. The modification of lipid A to tetra-acylated1,435/1,449 and/or penta-acylated1,690 fatty acids indicates poor growth conditions and bioavailability of hemin. Hemin protects P. gingivalis from serum resistance and the lipid A serves as a site for its binding. The LPS1,435/1,449 and LPS1,690 isoforms can produce opposite effects on the human Toll-like receptors (TLR) TLR2 and TLR4 activation. This enables P. gingivalis to select the conditions for its entry, survival, and that of its co-habiting species in the host, orchestrating its virulence to control innate immune pathway activation and biofilm dysbiosis. This review describes a number of effects that LPS1,435/1,449 and LPS1,690 can exert on the host tissues such as deregulation of the innate immune system, subversion of host cell autophagy, regulation of outer membrane vesicle production, and adverse effects on pregnancy outcome. The ability to change its LPS1,435/1,449 and/or LPS1,690 composition may enable P. gingivalis to paralyze local pro-inflammatory cytokine production, thereby gaining access to its primary location in periodontal tissue.

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“…Genes hemA, hemL, hemB and hemC encoding the enzymes that are involved in haem biosynthesis pathway cannot be identified in the genome of P. gingivalis [27]. While P. gingivalis can utilize haem from other sources such as serum albumin, transferrin, lactoferrin, haemopexin, catalase, lactoperoxidase and cytochrome [77][78], haemoglobin is the preferred haem and iron source [79].…”

Section: Gingipains In Haem Acquisitionmentioning

confidence: 99%

Gingipains fromPorphyromonas gingivalis— complex domain structures confer diverse functions

Li¹,

Collyer²

2011

European Journal of Microbiology and Immunology

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Gingipains, a group of arginine or lysine specific cysteine proteinases (also known as RgpA, RgpB and Kgp), have been recognized as major virulence factors in Porphyromonas gingivalis. This bacterium is one of a handful of pathogens that cause chronic periodontitis. Gingipains are involved in adherence to and colonization of epithelial cells, haemagglutination and haemolysis of erythrocytes, disruption and manipulation of the inflammatory response, and the degradation of host proteins and tissues. RgpA and Kgp are multi-domain proteins composed of catalytic domains and haemagglutinin/adhesin (HA) regions. The structure of the HA regions have previously been defined by a gingipain domain structure hypothesis which is a set of putative domain boundaries derived from the sequences of fragments of these proteins extracted from the cell surface. However, multiple sequence alignments and hidden Markov models predict an alternative domain architecture for the HA regions of gingipains. In this alternate model, two or three repeats of the socalled "cleaved adhesin" domains (and one other undefined domain in some strains) are the modules which constitute the substructure of the HA regions. Recombinant forms of these putative cleaved adhesin domains are indeed stable folded protein modules and recently determined crystal structures support the hypothesis of a modular organisation of the HA region. Based on the observed K2 and K3 structures as well as multiple sequence alignments, it is proposed that all the cleaved adhesin domains in gingipains will share the same β-sandwich jelly roll fold. The new domain model of the structure for gingipains and the haemagglutinin (HagA) proteins of P. gingivalis will guide future functional studies of these virulence factors.Keywords: Porphyromonas gingivalis, cleaved adhesin, gingipain, haemagglutinin, lysine-and arginine-specific cysteine proteases *Corresponding author: Charles A. Collyer; Phone: +61 293512794; Fax: +61 293514726; E-mail: charles.collyer@sydney.edu.au high as 50% [23]. P. gingivalis is a non-motile Gram-negative anaerobic bacillus [18]. In contrast to other members of the genus Porphyromonas, many of which are able to grow on complex carbohydrates, P. gingivalis is asaccharolytic and reliant upon nitrogenous substrates such as proteins or peptides as nutrients and for metabolic energy [24][25][26]. P. gingivalis is able to produce a large amount of proteinases to degrade proteins from host or other microorganisms in order to meet its special nutritional requirements [5,18]. Importantly, this bacterium needs exogenous haem for growth due to the lack of a haem biosynthesis pathway [27][28]. P. gingivalis is mostly found in bleeding chronic periodontal lesions, where haemoglobin from ruptured erythrocytes provides a very convenient and abundant haem source. When growing on blood agar plates P. gingivalis colonies are initially white to creamy in colour, but turn dark red to black after 6-10 days [26]. The black pigmentation has been verified as an accumulation of iron (...

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Roles of porphyrins and host iron transport proteins in regulation of growth of Porphyromonas gingivalis W50

Cited by 128 publications

References 54 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

Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signalling

Gingipains fromPorphyromonas gingivalis— complex domain structures confer diverse functions

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