Nefise AKÇELİK, Maryam DIANI, Mohammad Nima ARIAFAR

İnsan ve hayvan sağlığı açısından risk oluşturan enterokokal biyofilm yapısının doğası

Enterokoklar, genellikle komensali olarak değerlendirilseler de aynı zamanda fırsatçı patojendirler ve sığır mastitisinin yanı sıra nozokomiyal kan dolaşımı, ameliyat bölgesi ve üriner sistem enfeksiyonu etkenleri arasında yer alan ilk üç bakteriden biridir. Enterokok türleri içerisinde Enterococcus faecalis insan ve hayvanlardaki enterokokal enfeksiyonların %80-90'ından sorumludur. Geriye kalan Enterococcus spp. enfeksiyonlardan sorumlu olan tür ise Enterococcus faecium'dur. Biyofilm yapısı; bir ya da daha fazla mikroorganizma türünün karbonhidrat bir matriks ile bir arada tutulduğu, besinlerin taşınması ve atıkların uzaklaştırılması amacı ile su kanalları ihtiva eden yüksek organizasyonlu yapılardır. Biyofilm yapısı, ekzopolisakkarit ve protein film tabakası ile içerisinde bulunan mikroorganizmalar için bir kalkan görevi görür ve bu yapıdaki bakterileri öldürmek, planktonik formdaki bakterilere kıyasla çok daha zordur. Biyofilm yapısındaki bakterilerin fagositoz, antikor ve antibiyotiklere karşı 1000 kata kadar daha dirençli oldukları bilinmektedir. Enterokoklar; jelatinaz, agregasyon maddeleri, kapsül yapısı ve enterokokal yüzey proteini gibi biyofilm yapısına katılan çeşitli virülans faktörler sayesinde insanları ve evcil hayvanları enfekte ederler. Ayrıca, tedavide kullanılan vankomisin gibi antimikrobiyal maddelere karşı daha dirençli olduklarından eradikasyonları oldukça zordur. Enterokok türlerinin çoğu en az bir antibiyotiğe karşı dirençlidir ve biyofilm yapısının bu dirence katkıda bulunduğu düşünülmüktedir. Tüm dünyada oldukça önemli düzeyde enfeksiyona neden olan bu organizmanın eradikasyonunda daha etkin başarının eldesi için, biyofilm yapısının aşamalarının ve moleküler mekanizmalarının anlaşılması ve bu yapı esas alınarak yeni ilaç dozlarının ve tedavi yollarının belirlenmesi gerekmektedir.

The nature of enterococcal biofilm structure, a risk factor for human and animal health

Enterococci, generally considered as normal bowel commensals, are also recognized as opportunistic pathogens and one of the top three bacterias which are the causes of bowine mastitis, nosocomial bloodstream, surgical site, and urinary tract infections as well. Enterococcus faecalis is the most common enterococci species, and it is responsible for 80-90% of human and animal enterococcal infections. Enterococcus faecium accounts for the remainder of infections caused by Enterococcus spp. Biofilms are highly organized structures formed by one or more microorganism species bound together by a carbonhydrate matrix that contain water channels to deliver nutrients and removes wastes. Biofilm structure works as a shield with its exopolysaccharide and protein film layer and often harder to kill them than their planktonic counterparts. Biofilm bacteria are up to 1000 times more resistant to phagocytosis, antibodies and antibiotics. Enterococci can infect humans and domestic animals because of their many virulence factors associated with biofilm formation including gelatinase, aggregation substance, capsule formation, enterococcal surface protein. Furthermore, since they are also resistant against antibiotics such as vancomycin that used at treatment, it is really difficult to eradicate. Many strains of enterococci are resistant to one or more antibiotics and biofilms are thought to contribute to this resistance. In all over the world, to achieve better results at eradication of thisorganism; structure and molecular mechanism of biofilm need to be understood for determination of new drug dosages and new treatment strategies to eradicate biofilm.

PDF

___

1. Murcia JA, Collins MD. Enterococcus sulfureus, a new yellow-pigment ed Enterococcus species. FEMS Microbiol Lett, 1991; 64: 69-74.
2. Murray BE, Weinstock GM. Enterococci: new aspects of an old organism. Proc Assoc Am Physicians, 1999; 111: 328-334.
3. Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in combined medicalsurgical intensive care units in the United States. Infect Control Hosp Epidemiol, 2002; 1: 510-5.
4. Donlan RM. Biofilms: microbial life on surfaces. Emerg Infect Dis, 2002; 8: 881-90.
5. Olson ME, Ceri H, Douglas W. Biyofilm bacteria: formation and comparative susceptibility to antibiotics. Can J Vet Res, 2002; 66: 86-92.
6. Ira P, Sujatha S, Chandra PS. Virulence factors in clinical and commensal isolates of Enterococcus species. Indian J Pathol Microbiol, 2013; 56: 24-30.
7. Jones M E, Draghi DC, Thornsberry C, Karlowsky JA, Sahm DF, Wenzel RP. Emerging resistance among bacterial pathogens in the intensive care unit - a European and North American Surveillance study 2000-2002. Ann Clin Microbiol Antimicrob, 2004; 3: 14.
8. Moellering RC. Jr: Enterococcus species, Streptococcus bovis and Leuconostoc species. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed, Philadelphia: Churchill Livingstone, 1999: 2411- 241.
9. Sood S, Malhotra M, Das BK, Kapil A. Enterococcal infections & antimicrobial resistance. Indian J Med Res, 2008; 128: 111-21.
10. Seno Y, Kariyama R, Mitsuhata R, Monden K, Kumon H. Clinical implications of biofilm formation by Enterococcus faecalis in the urinary tract. Acta Med Okayama, 2005; 59: 79-87.
11. Edmond MB, Ober JF, Dawson JD. Vancomycinresistant enterococcal bacteremia: Natural history and attributable mortality. Clin Infect, 1996; 23: 1234.
12. Sutherland IW. Biofilm exopolysaccharites: A strong and sticky framework. Microbiol, 2001; 147: 3-9.
13. Post JC, Stoodley P, Hall-Stoodley L, Ehrlich GD. The role of biofilms in otolaryngologic infections. Curr Opin Otolaryngol Head Neck Surg, 2004; 12: 185-90.
14. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infection. Science, 1999; 284: 1318-22.
15. Davey ME, O'toole GA. Microbial biofilms: from ecology to molecular genetics. Microbiol Mol Biol Rev, 2000; 64: 847-67.
16. Bothwell MR, Smith AL, Phillips T. Recalcitrant otorrhea due to Pseudomonas biofilm. Otolaryngol Head Neck Surg, 2003; 129: 599-60.
17. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev, 2002; 15: 167-93 . 18. Palmer R Jr, White DC. Developmental biology of biofilms: implications for treatment and control. Trends Microbiol, 1997; 5: 435-40.
19. http://en.wikipedia.org/wiki/File:Biofilm_ Biofilm Formation: Formation.jpg (Erişim tarihi: Nisan 2015)
20. Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappinscott HM. Microbial biofilms. Annu Rev Microbiol, 1995; 49: 711-45.
21. Poulsen LV. Microbial biofilm in food proces¬sing. Lebensm Wiss u Techn, 1999; 32: 321-6.
22. Rosenberg M, Perry A, Bayer EA, Gutnick DL, Rosenberg E, Ofek I. Adherence of Acinetobacter calcoaceticus RAG-1 to human epithelial cells and to hexadecane. Infect Immun, 1981; 33: 29-33.
23. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science, 1994; 284: 1318-22.
24. Kreft JU, Wimpenny JWT. Effect of EPS on biofilm structure and function as revealed by an individual-based model of biofilm growth. Water Sci Technol, 2001; 43: 135-41.
25. Hoiby N. New antimicrobials in the management of cystic fibrosis. J Antimicrob Chemother, 2002; 49: 235-8.
26. Fisher K, Phillips, C. The ecology, epidemiology and virulence of Enterococcus. Microbiol, 2009; 155: 1749-57.
27. Noble WC, Virani Z, Cree RG. Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. Fems Microbiol Lett, 1992; 72: 195-198.
28. Chang S, Sievert DM, Hageman JC, Boulton ML, Tenover FC, Downes FP. Infection with vancomycinresistant Staphylococcus aureus containing the vanA resistance gene. N Engl J Med, 2003; 348: 1342- 1347.
29. Fux CA, Costerton JW, Stewart PS, Stoodley P. Survival strategies of infectious biofilms. Trens Microbiol, 2005; 13: 34-40.
30. Carniol K, Gilmore MS. Signal transduction, quorum-sensing, and extracellular protease activity in Enterococcus faecalis biofilm formation. J Bacteriol, 2004; 186: 8161-3.
31. Pillai SK, Sakoulas G, Eliopoulos GM, Moellering RC Jr, Murray BE, Inouye RT. Effects of glucose on fsr-mediated biofilm formation in Enterococcus faecalis. J Infect Dis, 2004; 190: 967-970.
32. Marinho AR, Martins PD, Ditmer EM, d'Azevedo PA, Frazzon J, Van Der Sand ST, et al. Biofilm formation on polystyrene under different temperatures by antibiotic resistant Enterococcus faecalis and Enterococcus faecium isolated from food. Braz J Microbiol, 2013; 44: 423-6.
33. Baldassarri L, Bertuccini L, Ammendolia MG, Arciola CR, Montanaro L. Effect of iron limitation on slime production by Staphylococcus aureus. Eur J Clin Microbiol Infect Dis, 2001; 20: 343-5.
34. Kristich CJ, Li YH, Cvitkovitch DG, Dunny GM. Espindependent biofilm formation by Enterococcus faecalis. J Bacteriol, 2004; 186: 154-63.
35. Diani M, Gunay Esiyok O, Ariafar MN, Yuksel FN, Gunes Altuntas E, Akcelik N. The interactions between esp, fsr, gelE genes and biofilm formation and pfge analysis of clinical Enterococcus faecium strains. Afr J Microbiol Res, 2014; 8(2): 129-37.
36. Tendolkar PM, Baghdayan AS, Gilmore MS, Shankar N. Enterococcal surface protein, Esp, enhances biofilm formation by Enterococcus faecalis. Infect Immun, 2004; 72: 6032-9.
37. Tendolkar PM, Baghdayan AS, Shankar N. Putative surface proteins encoded within a novel transferable locus confer a high-biofilm phenotype to Enterococcus faecalis. J Bacteriol, 2006; 188: 2063-72.
38. Arias CA, Panesso D, Singh KV, Rice LB, Murray BE. Cotransfer of antibiotic resistance genes and a hylEfm-containing virulence plasmid in Enterococcus faecium. Antimicrob Agents Chemother, 2009; 53: 4240-6.
39. Willems RJ, van Schaik W. Transition of Enterococcus faecium from commensal organism to nosocomial pathogen. Future Microbiol, 2009; 4: 1125-35.
40. Mohamed JA, Huang DB. Biofilm formation by enterococci. J Med Microbiol, 2007; 56: 1581-8.
41. Budzik JM, Schneewind O. Pili prove pertinent to Enterococcal endocarditis. Invest, 2006; 116: 2582-4.
42. Nallapareddy SR, Singh KV, Sillanpää J, Garsin DA, Höök M, Erlandsen SL, et al. Endocarditis and biofilm-associated pili of Enterococcus faecalis. J Clin Invest, 2006; 116: 2799-807.
43. Qin X, Singh KV, Weinstock GM, Murray BE. Characterization of fsr, a regulator controlling expression of gelatinase and serine protease in Enterococcus faecalis OG1RF. J Bacteriol, 2001; 183: 3372-82.
44. Singh KV, Qin X, Weinstock GM, Murray BE. Generation and testing of mutants of Enterococcus faecalis in a mouse peritonitis model. J Infect Dis, 1998; 178: 1416-20.
45. Engelbert M, Mylonakis E, Ausubel FM, Calderwood SB, Gilmore MS. Contribution of gelatinase, serine protease, and fsr to the pathogenesis of Enterococcus faecalis endophthalmitis. Infect Immun, 2004; 72: 3628-33.
46. Mohamed JA, Singh KV, Huang W, Teng F, Murray BE. Influence of clinical origin and of various genes on biofilm formation by Enterococcus faecalis. In Program Abstracts of the 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, abstract B-821, p. 52, Washington, DC, 2003.
47. Hancock LE, Perego M. The Enterococcus faecalis fsr two-component system controls biofilm development through production of gelatinase. J Bacteriol, 2004; 186: 5629-39.
48. Baldassarri L, Creti R, Recchia S, Pataracchia M, Alfarone G, Orefici G, et al. Virulence factors in enterococcal infections of orthopedic devices. Int J Artif Organs, 2006; 29: 402-6.
49. Qin X, Singh KV, Weinstock GM, Murray BE. Effects of Enterococcus faecalis fsr genes on production of gelatinase and a serine protease and virulence. Infect Immun, 2000; 68: 2579-86.
50. Dunman PM, Murphy E, Haney S. Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci. J Bacteriol, 2001; 183: 7341-53.
51. Mohamed JA, Huang W, Nallapareddy SR, Teng F, Murray BE. Influence of origin of isolates, especially endocarditis isolates, and various genes on biofilm formation by Enterococcus faecalis. Infect Immun, 2004; 72: 3658-63.
52. Hufnagel M, Koch S, Creti R, Baldassarri L, Huebner J. A putative sugar-binding transcriptional regulator in a novel gene locus in Enterococcus faecalis contributes to production of biofilm and prolonged bacteremia in mice. J Infect Dis, 2004; 189: 420-30.
53. Mohamed JA, Teng F, Nallapareddy SR, Murray BE. Pleiotrophic effects of 2 Enterococcus faecalis sagA-like genes, salA and salB, which encode proteins that are antigenic during human infection, on biofilm formation and binding to collagen type I and fibronectin. J Infect Dis, 2006; 193: 231-40.