Antibacterial effects of sodium tripolyphosphate against Porphyromonas species associated with periodontitis of companion animals

다국어 초록 (Multilingual Abstract)

Porphyromonas species are closely associated with companion animal periodontitis which is one of the most common diseases in dogs and cats and leads to serious systemic diseases if left untreated. In this study, we evaluated the antimicrobial effects and mode of action of sodium tripolyphosphate (polyP3, Na5P3O10), a food additive with proven safety, using three pathogenic Porphyromonas species. The minimum inhibitory concentrations (MICs) of polyP3 against Porphyromonas gulae, Porphyromonas cansulci, and Porphyromonas cangingivalis were between 500 and 750 mg/L. PolyP3 significantly decreased viable planktonic cells as well as bacterial biofilm formation, even at sub-MIC concentrations. PolyP3 caused bacterial membrane disruption and this effect was most prominent in P. cangingivalis, which was demonstrated by measuring the amount of nucleotide leakage from the cells. To further investigate the mode of action of polyP3, high-throughput whole-transcriptome sequencing was performed using P. gulae. Approximately 30% of the total genes of P. gulae were differentially expressed by polyP3 (> 4-fold, adjusted p value < 0.01). PolyP3 influenced the expression of the P. gulae genes related to the biosynthesis of thiamine, ubiquinone, and peptidoglycan. Collectively, polyP3 has excellent antibacterial effects against pathogenic Porphyromonas species and can be a promising agent to control oral pathogenic bacteria in companion animals.

참고문헌 (Reference)

1 Raschke M, "Vitamin B1 biosynthesis in plants requires the essential iron sulfur cluster protein, THIC" 104 : 19637-19642, 2007

2 Ng WL, "Transcriptional regulation and signature patterns revealed by microarray analyses of Streptococcus pneumoniae R6 challenged with sublethal concentrations of translation inhibitors" 185 : 359-370, 2003

3 Winkler W, "Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression" 419 : 952-956, 2002

4 Du Q, "Thiamin(vitamin B1)biosynthesis and regulation : a rich source of antimicrobial drug targets" 7 : 41-52, 2011

5 Cummins CS, "The chemical composition of the cell wall in some gram-positive bacteria and its possible value as a taxonomic character" 14 : 583-600, 1956

6 Finn RD, "The Pfam protein families database: towards a more sustainable future" D1 : D279-D285, 2016

7 Serganov A, "Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch" 441 : 1167-1171, 2006

8 Harvey CE, "Small Animal Dentistry" Mosby-Year Books 1993

9 Allaker RP, "Prevalence of Porphyromonas and Prevotella species in the dental plaque of dogs" 140 : 147-148, 1997

10 Fournier D, "Porphyromonas gulae sp. nov., an anaerobic, gram-negative coccobacillus from the gingival sulcus of various animal hosts" 51 : 1179-1189, 2001

11 Darveau RP, "Porphyromonas gingivalis as a potential community activist for disease" 91 : 816-820, 2012

12 Collins MD, "Phylogenetic analysis of members of the genus Porphyromonas and description of Porphyromonas cangingivalis sp. nov. and Porphyromonas cansulci sp. nov" 44 : 674-679, 1994

13 Ritz E, "Phosphate additives in food--a health risk" 109 : 49-55, 2012

14 Harvey CE, "Periodontal disease in dogs. Etiopathogenesis, prevalence, and significance" 28 : 1111-1128, 1998

15 Bodet C, "Pathogenic potential of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, the red bacterial complex associated with periodontitis" 55 : 154-162, 2007

16 Ximénez-Fyvie LA, "Microbial composition of supra-and subgingival plaque in subjects with adult periodontitis" 27 : 722-732, 2000

17 Socransky SS, "Microbial complexes in subgingival plaque" 25 : 134-144, 1998

18 Moon JH, "Microarray analysis of the transcriptional responses of Porphyromonas gingivalis to polyphosphate" 14 : 218-, 2014

19 Emerson JE, "Microarray analysis of the transcriptional responses of Clostridium difficile to environmental and antibiotic stress" 57 : 757-764, 2008

20 Clinical and Laboratory Standards Institute (CLSI), "Methods for antimicrobial susceptibility testing of anaerobic bacteria. Approved standard-seventh edition"

21 Okuda K, "Involvement of periodontopathic biofilm in vascular diseases" 10 : 5-12, 2004

22 Kornberg A, "Inorganic polyphosphate : a molecule of many functions" 68 : 89-125, 1999

23 Maguire BA, "Inhibition of bacterial ribosome assembly: a suitable drug target?" 73 : 22-35, 2009

24 Knabel SJ, "Inhibition of Aspergillus flavus and selected gram-positive bacteria by chelation of essential metal cations by polyphosphates" 54 : 360-365, 1991

25 Jang EY, "In vitro effects of polyphosphate against Prevotella intermedia in planktonic phase and biofilm" 60 : 818-826, 2015

26 문지회, "In vitro effects of N-acetyl cysteine alone and in combination with antibiotics on Prevotella intermedia" 한국미생물학회 53 (53): 321-329, 2015

27 Deshpande SS, "Handbook of Food Toxicology" Marcel Dekker 258-261, 2002

28 Lanigan RS, "Final report on the safety assessment of sodium metaphosphate, sodium trimetaphosphate, and sodium hexametaphosphate" 20 (20): 75-89, 2001

29 Mikkola R, "Evidence for demand-regulation of ribosome accumulation in E coli" 73 : 1551-1556, 1991

30 Slots J, "Effective, safe, practical and affordable periodontal antimicrobial therapy : where are we going, and are we there yet" 28 : 298-312, 2002

31 Isogai H, "Ecology of genus Porphyromonas in canine periodontal disease" 46 : 467-473, 1999

32 Ellinger RH, "CRC Handbook of Food Additives" CRC Press 617-780, 1972

33 Dahlén GG, "Black-pigmented gram-negative anaerobes in periodontitis" 6 : 181-192, 1993

34 Bartlett PN, "Bioelectrochemistry: Fundamentals, Experimental Techniques and Applications" John Wiley & Sons Ltd 1-32, 2008

35 Scannapieco FA, "Associations between periodontal disease and risk for nosocomial bacterial pneumonia and chronic obstructive pulmonary disease. A systematic review" 8 : 54-69, 2003

36 DeBowes LJ, "Association of periodontal disease and histologic lesions in multiple organs from 45 dogs" 13 : 57-60, 1996

37 Lee RM, "Antibacterial mechanism of long-chain polyphosphates in Staphylococcus aureus" 57 : 289-294, 1994

38 Moon JH, "Antibacterial action of polyphosphate on Porphyromonas gingivalis" 55 : 806-812, 2011

39 Stephan B, "Activity of pradofloxacin against Porphyromonas and Prevotella spp. Implicated in periodontal disease in dogs: susceptibility test data from a European multicenter study" 52 : 2149-2155, 2008

40 Davis IJ, "A cross-sectional survey of bacterial species in plaque from client owned dogs with healthy gingiva, gingivitis or mild periodontitis" 8 : e83158-, 2013