Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways

Fischer, Carol L.; Dawson, Deborah V.; Blanchette, Derek R.; Drake, David R.; Wertz, Philip W.; Brogden, Kim A.

doi:10.1128/jb.00665-15

Cited by 6 publications

(9 citation statements)

References 71 publications

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“…Treatment of P. gingivalis with sapienic acid produced statistically significant overrepresentation of proteins involved in respiration, metabolism, energy production, iron acquisition and processing, and lipid biosynthesis, when compared to healthy, untreated bacteria. Further studies by this group suggested that along with the expected increase in proteins related to energy production, iron acquisition and processing, and respiration, and the decrease in some virulence proteins, sapienic acid treated P. gingivalis also showed an increase in proteins related to lipid metabolism [59]. Because endogenous P. gingivalis cell membrane phospholipids contain branched fatty acids of approximately the same length as sapienic acid, it may be possible for sapienic acid to be incorporated into newly synthesized P. gingivalis phospholipids, which would alter the fluidity of the membrane.…”

Section: Aml Lipid Mechanismsmentioning

confidence: 96%

“…Sapienic acid is more effective than lauric acid against all oral bacteria tested, including P. gingivalis and F. nucleatum [37,38] . P. gingivalis rapidly takes up sapienic acid and induces upregulation of proteins involved in multiple cellular processes, including lipid metabolism, and killing P. gingivalis in less than six minutes [37,59]. Scanning and transmission micrographs of treated and untreated bacteria demonstrate that sapienic acid also triggers creation of pores in the P. gingivalis cell membrane, flocculation of intracellular contents, alteration of the cellular membrane, and lysis of cells.…”

Section: Fatty Acids As Amlsmentioning

confidence: 99%

“…Sphingoid bases are also broadly active against oral bacteria (Table 3). Fischer and colleagues [36,37,59] tested sphingoid bases, sphingosine, dihydrosphingosine, and phytosphingosine, against a wide variety of Gram positive and Gram negative bacteria, including E. coli, S. aureus, S. sanguinis, Streptococcus mitis, Corynebacterium striatum, Corynebacterium jeikeium, A. actinomycetemcomitans, F. nucleatum, and P. gingivalis using minimum inhibitory concentrations (MIC), minimum bactericidal concentrations, and kill kinetics assays. Sphingoid bases were widely active against Gram positive bacteria and some Gram negative oral species of bacteria with variable and specific activity.…”

Section: Sphingoid Bases As Amlsmentioning

confidence: 99%

“…Recent studies demonstrate differential protein regulation in P. gingivalis when treated with sapienic acid [37,59]. Treatment of P. gingivalis with sapienic acid produced statistically significant overrepresentation of proteins involved in respiration, metabolism, energy production, iron acquisition and processing, and lipid biosynthesis, when compared to healthy, untreated bacteria.…”

Section: Aml Lipid Mechanismsmentioning

confidence: 99%

“…This study suggests that while trying to overcome excessive sapienic acid uptake, P. gingivalis increased energy production and fatty acid biosynthesis, possibly to compete with insertion of toxic fatty acid species into the bacterial plasma membrane. Increased fatty acid biosynthesis is supported by evidence of preferential serine metabolism, which is an important intermediate for sphingoid bases present in P. gingivalis membranes [98][99][100], and significant increases in FabH and FabF, proteins associated with the FAS-II fatty acid biosynthesis pathway [59].…”

Section: Aml Lipid Mechanismsmentioning

confidence: 99%

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Antimicrobial Activity of Host-Derived Lipids

Fischer

2020

Antibiotics

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Host-derived lipids are increasingly recognized as antimicrobial molecules that function in innate immune activities along with antimicrobial peptides. Sphingoid bases and fatty acids found on the skin, in saliva and other body fluids, and on all mucosal surfaces, including oral mucosa, exhibit antimicrobial activity against a variety of Gram positive and Gram negative bacteria, viruses, and fungi, and reduce inflammation in animal models. Multiple studies demonstrate that the antimicrobial activity of lipids is both specific and selective. There are indications that the site of action of antimicrobial fatty acids is the bacterial membrane, while the long-chain bases may inhibit cell wall synthesis as well as interacting with bacterial membranes. Research in this area, although still sporadic, has slowly increased in the last few decades; however, we still have much to learn about antimicrobial lipid mechanisms of activity and their potential use in novel drugs or topical treatments. One important potential benefit for the use of innate antimicrobial lipids (AMLs) as antimicrobial agents is the decreased likelihood side effects with treatment. Multiple studies report that endogenous AML treatments do not induce damage to cells or tissues, often decrease inflammation, and are active against biofilms. The present review summarizes the history of antimicrobial lipids from the skin surface, including both fatty acids and sphingoid bases, in multiple human body systems and summarizes their relative activity against various microorganisms. The range of antibacterial activities of lipids present at the skin surface and in saliva is presented. Some observations relevant to mechanisms of actions are discussed, but are largely still unknown. Multiple recent studies examine the therapeutic and prophylactic uses of AMLs. Although these lipids have been repeatedly demonstrated to act as innate effector molecules, they are not yet widely accepted as such. These compiled data further support fatty acid and sphingoid base inclusion as innate effector molecules.

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Section: Aml Lipid Mechanismsmentioning

confidence: 96%

Section: Fatty Acids As Amlsmentioning

confidence: 99%

Section: Sphingoid Bases As Amlsmentioning

confidence: 99%

Section: Aml Lipid Mechanismsmentioning

confidence: 99%

Section: Aml Lipid Mechanismsmentioning

confidence: 99%

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Antimicrobial Activity of Host-Derived Lipids

Fischer

2020

Antibiotics

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Fatty acids and related lipid mediators in the regulation of cutaneous inflammation

Kiezel-Tsugunova

Kendall

Nicolaou

2018

Biochemical Society Transactions

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Human skin has a distinct profile of fatty acids and related bioactive lipid mediators that regulate many aspects of epidermal and dermal homeostasis, including immune and inflammatory reactions. Sebum lipids act as effective antimicrobial agents, shape immune cell communications and contribute to the epidermal lipidome. The essential fatty acid linoleic acid is crucial for the structure of the epidermal barrier, while polyunsaturated fatty acids act as precursors to eicosanoids, octadecanoids and docosanoids through cyclooxygenase, lipoxygenase and cytochrome P450 monooxygenase-mediated reactions, and endocannabinoids and -acyl ethanolamines. Cross-communication between these families of bioactive lipids suggests that their cutaneous activities should be considered as part of a wider metabolic network that can be targeted to maintain skin health, control inflammation and improve skin pathologies.

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Bile acid fitness determinants of aBacteroides fragilisisolate from a human pouchitis patient

Fiebig,

Schnizlein,

Pena-Rivera

et al. 2023

Preprint

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Bacteroides fragiliscomprises 1-5% of the gut microbiota in healthy individuals but can expand to >50% of the population in ulcerative colitis (UC) patients experiencing inflammation. The mechanisms underlying such microbial blooms are poorly understood, but the gut of UC patients has physicochemical features that differ from healthy patients and that likely impact microbial growth and community structure. In UC colectomy patients with surgically created ileoanal pouches, levels of the bile acid deoxycholate (DC) are reduced in the pouch. We developed aB. fragilisstrain isolated from a UC patient with pouch inflammation (i.e. pouchitis) as a genetic model system and have used this strain to identify genes and pathways that impact fitness in DC and crude bile. Treatment ofB. fragiliswith a DC concentration congruent with a healthy human gut reduced cell growth and remodeled transcription of approximately one-quarter of all genes. DC strongly induced transcription of chaperones and select transcriptional regulators and efflux systems and downregulated protein synthesis genes. We further definedB. fragilisgenes that impacted fitness in media containing DC or crude bile using a barcoded collection of ≈50,000 unique mutants. Genes that contribute to cell envelope functions including cardiolipin synthesis, cell surface glycosylation, and systems implicated in sodium-dependent bioenergetics were major bile acid fitness factors. The correspondence between genes that were transcriptionally regulated and genes that impacted fitness in bile was limited. Our study provides a genome-scale view of aB. fragilisbile response and genetic determinants of fitness in DC and crude bile.

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Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways

Cited by 6 publications

References 71 publications

Antimicrobial Activity of Host-Derived Lipids

Antimicrobial Activity of Host-Derived Lipids

Fatty acids and related lipid mediators in the regulation of cutaneous inflammation

Bile acid fitness determinants of aBacteroides fragilisisolate from a human pouchitis patient

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