2‐Hydroxyisocaproic acid is bactericidal in human dental root canals <i>ex vivo</i>

Sakko, Marjut; Tjäderhane, Leo; Sorsa, Timo; Hietala, Pentti K.; Rautemaa, Riina

doi:10.1111/iej.12639

Cited by 15 publications

(14 citation statements)

References 48 publications

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“…39 An amino acid derivative 2-hydroxyisocaproic acid (HICA) with broad-spectrum antimicrobial activity could also be potential alternative for endodontic use. 40,41 Safe agents with new mode of actions and suitable physical properties for long lasting antimicrobial activity are needed for interappointment medication.…”

Section: Future Perspectivesmentioning

confidence: 99%

Microbiology of Root Canal Infections

2016

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Inflammatory reaction in the periapical tissues is induced by microbial infection in the root canal system. The aim of root canal treatment is to preserve healthy periapical tissues or to provide healing of them in restorable teeth, which have sufficient periodontal support. The amount of microbial cells in the root canal system and their virulence as well as host responses influence on the degree of periapical inflammation and symptoms. Microbial biofilm formation is typically seen on root canal walls but some microbial species are able to invade the dentine tubules to varying depth. In prolonged and complicated infections, or in case of risk of systemic spread of infection, root canal sampling for microbiological diagnostics is recommended. Anaerobic gram-negative rods are commonly isolated organisms in primary infections. In post-treatment disease, the microflora is dominated by facultatively anaerobic gram-positive cocci and rods such as Streptococcus, Enterococcus, Peptostreptococcus and Actinomyces species. Instrumentation, disinfection and interappointment medication in strict aseptic conditions are essential steps for eradication of microbial species from the infected root canal system. During past decades, Enterococcus faecalis and Candida albicans have been commonly associated organisms in treatment-resistant infections. Novel microbial detection methods are giving increasing knowledge about microbial species associated with endodontic infections and their roles in them.

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Section: Future Perspectivesmentioning

confidence: 99%

Microbiology of Root Canal Infections

2016

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“…A previous report showed that the Lactobacillus amylovorus DSM19280 (cereal isolate), Lactobacillus brevis R2Δ (porcine isolate), and Lactobacillus reuteri R29 strains produce HICA and characterized their antifungal activities 26 . HICA exhibits mild fungicidal or antibiotic activity against Candida , Aspergillus , Staphylococcus , and Fusobacterium 27 , 28 and also shows activity against Enterococcus faecalis isolated from human teeth 29 . In a murine model, HICA attenuated inflammatory responses during Candida infection 25 .…”

Section: Discussionmentioning

confidence: 99%

Identification of 2-hydroxyisocaproic acid production in lactic acid bacteria and evaluation of microbial dynamics during kimchi ripening

Park¹,

Hwang²,

Chang³

et al. 2017

Sci Rep

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Lactic acid bacteria produce diverse functional metabolites in fermented foods. However, little is known regarding the metabolites and the fermentation process in kimchi. In this study, the culture broth from Leuconostoc lactis, a lactic acid bacterium isolated from kimchi, was analysed by liquid chromatography-tandem mass spectrometry and identified by the MS-DIAL program. The MassBank database was used to analyse the metabolites produced during fermentation. A mass spectrum corresponding to 2-hydroxyisocaproic acid (HICA) was validated based on a collision-induced dissociation (CID) fragmentation pattern with an identified m/z value of 131.07. HICA production by lactic acid bacteria was monitored and showed a positive correlation with hydroxyisocaproate dehydrogenases (HicDs), which play a key role in the production of HICA from leucine and ketoisocaproic acid. Interestingly, the HICA contents of kimchi varied with Leuconostoc and Lactobacillus content during the early stage of fermentation, and the addition of lactic acid bacteria enhanced the HICA content of kimchi. Our results suggest that HICA production in kimchi is dependent on the lactic acid bacterial composition.

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“…vaginalis also produces very high levels of HICA suggesting that catabolism of leucine by this route is important to the organism. HICA is produced by lactic acid bacteria and was recently shown to have antimicrobial [ 75 – 77 ] and anti-inflammatory activity [ 78 ]. HICA can also improve muscle recovery by inducing an increase in protein synthesis through mTOR signalling [ 79 ], which also regulates the innate immune response to bacterial, fungal or parasitic infection.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine

et al. 2017

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Trichomonas vaginalis and Tritrichomonas foetus are pathogens that parasitise, respectively, human and bovine urogenital tracts causing disease. Using LC-MS, reference metabolomic profiles were obtained for both species and stable isotope labelling with D-[U-13C6] glucose was used to analyse central carbon metabolism. This facilitated a comparison of the metabolic pathways of T. vaginalis and T. foetus, extending earlier targeted biochemical studies. 43 metabolites, whose identities were confirmed by comparison of their retention times with authentic standards, occurred at more than 3-fold difference in peak intensity between T. vaginalis and T. foetus. 18 metabolites that were removed from or released into the medium during growth also showed more than 3-fold difference between the species. Major differences were observed in cysteine and methionine metabolism in which homocysteine, produced as a bi-product of trans-methylation, is catabolised by methionine γ-lyase in T. vaginalis but converted to cystathionine in T. foetus. Both species synthesise methylthioadenosine by an unusual mechanism, but it is not used as a substrate for methionine recycling. T. vaginalis also produces and exports high levels of S-methylcysteine, whereas only negligible levels were found in T. foetus which maintains significantly higher intracellular levels of cysteine. 13C-labeling confirmed that both cysteine and S-methylcysteine are synthesised by T. vaginalis; S-methylcysteine can be generated by recombinant T. vaginalis cysteine synthase using phosphoserine and methanethiol. T. foetus contained higher levels of ornithine and citrulline than T. vaginalis and exported increased levels of putrescine, suggesting greater flux through the arginine dihydrolase pathway. T. vaginalis produced and exported hydroxy acid derivatives of certain amino acids, particularly 2-hydroxyisocaproic acid derived from leucine, whereas negligible levels of these metabolites occurred in T. foetus.

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2‐Hydroxyisocaproic acid is bactericidal in human dental root canals ex vivo

Abstract: HICA paste exerted superior activity against E. faecalis and could have potential for root canal medication.

Cited by 15 publications

References 48 publications

Microbiology of Root Canal Infections

Microbiology of Root Canal Infections

Identification of 2-hydroxyisocaproic acid production in lactic acid bacteria and evaluation of microbial dynamics during kimchi ripening

Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine

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