Structural confirmation of the dihydrosphinganine and fatty acid constituents of the dental pathogen Porphyromonas gingivalis

Mun, Ji Young; Onorato, Amber; Nichols, Frank C.; Morton, Martha D.; Saleh, Abdullah; Welzel, Morgan; Smith, Michael B.

doi:10.1039/b712707c

Cited by 20 publications

(12 citation statements)

References 45 publications

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“…To calculate the percentage of lipid uptake for each sample we divided the total extracted lipid weight by the total weight of lipid added to each sample. Because P. gingivalis plasma membrane naturally contains dihydrosphingosine, 32,33,34,35 total sphingoid base lipids were normalized by subtracting the total sphingoid base weight present in the untreated P. gingivalis controls.…”

Section: Methodsmentioning

confidence: 99%

Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

et al. 2013

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Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria; however, little is known about their spectrum of antimicrobial activity or mechanisms of action against oral bacteria. In this study, we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Minimal inhibitory concentrations, minimal bactericidal concentrations, and kill kinetics revealed variable, but potent, activity of oral mucosal and salivary lipids against P. gingivalis, indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria, although specific components of bacterial membranes are also likely important. Electron micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma membrane. This information, coupled with the association of treatment lipids with P. gingivalis lipids revealed via thin layer chromatography, suggests that the plasma membrane is a likely target of lipid antibacterial activity. Utilizing a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique P. gingivalis stress response, including proteins important in fatty acid biosynthesis, metabolism and energy production, protein processing, cell adhesion and virulence. Prophylactic or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

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Section: Methodsmentioning

confidence: 99%

Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

et al. 2013

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“…In contrast to higher order organisms, relatively few studies have been carried out to investigate the role of SL biosynthesis and metabolism in bacterial species. Of these, it is interesting to note that microbes from the human microbiome, P. gingivalis from the oral cavity and the gut commensal B. fragilis , make SLs with unusual structural features (14–16). Their roles in bacterial metabolism, as well as their interaction within the host environment, are currently under investigation (48).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the number of bacteria that produce SLs, examples being Sphingomonas spp (12) and Myxobacterium spp (13), is relatively small. However, it is interesting to note that many of the bacteria that are part of the human microbiome, such as Bacteroides fragilis and Porphyromonas gingivalis , also produce SLs (14–16). This raises the interesting question of what is the function of bacterial SLs?…”

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confidence: 99%

Characterization of homologous sphingosine-1-phosphate lyase isoforms in the bacterial pathogen Burkholderia pseudomallei

McLean

Marles‐Wright

Custódio

et al. 2017

Journal of Lipid Research

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Sphingolipids (SLs) are ubiquitous elements in eukaryotic membranes and are also found in some bacterial and viral species. As well as playing an integral structural role, SLs also act as potent signaling molecules involved in numerous cellular pathways and have been linked to many human diseases. A central SL signaling molecule is sphingosine-1-phosphate (S1P), whose breakdown is catalyzed by S1P lyase (S1PL), a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyzes the cleavage of S1P to (2E)-hexadecenal (2E-HEX) and phosphoethanolamine. Here, we show that the pathogenic bacterium, Burkholderia pseudomallei K96243, encodes two homologous proteins (S1PL2021 and S1PL2025) that display moderate sequence identity to known eukaryotic and prokaryotic S1PLs. Using an established MS-based methodology, we show that recombinant S1PL2021 is catalytically active. We also used recombinant human fatty aldehyde dehydrogenase to develop a spectrophotometric enzyme-coupled assay to detect 2E-HEX formation and measure the kinetic constants of the two B. pseudomallei S1PL isoforms. Furthermore, we determined the X-ray crystal structure of the PLP-bound form of S1PL2021 at 2.1 Å resolution revealing that the enzyme displays a conserved structural fold and active site architecture comparable with known S1PLs. The combined data suggest that B. pseudomallei has the potential to degrade host SLs in a S1PL-dependent manner.

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“…This organism is thought to be a major periodontal pathogen associated with inflammatory periodontal disease in adults [46]. …”

Section: Patho-biological Functions Of Microbial 3-hydroxy Oxylipinsmentioning

confidence: 99%

The presence of 3-hydroxy oxylipins in pathogenic microbes

Sebolai

Pohl

Kock

et al. 2012

Prostaglandins & Other Lipid Mediators

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There is a sufficient body of work documenting the distribution of 3-hydroxy oxylipins in microbes. However, there is limited information on the role of these compounds in microbial pathogenesis. When derived from mammalian cells, these compounds regulate patho-biological processes, thus an understanding of 3-hydroxy oxylipin function and metabolism could prove important in shedding light on how these compounds mediate cellular pathology and physiology. This could present 3-hydroxy oxylipin biosynthetic pathways as targets for drug development. In this minireview, we interrogate the relevant yeast and bacterial 3-hydroxy oxylipin literature in order to appreciate how these compounds may influence the inflammatory response leading to disease development.

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Structural confirmation of the dihydrosphinganine and fatty acid constituents of the dental pathogen Porphyromonas gingivalis

Cited by 20 publications

References 45 publications

Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

Characterization of homologous sphingosine-1-phosphate lyase isoforms in the bacterial pathogen Burkholderia pseudomallei

The presence of 3-hydroxy oxylipins in pathogenic microbes

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