09-18-2013, 09:29 PM
(This post was last modified: 09-18-2013, 09:44 PM by Administrator.)
Biofilms and Cystic fibrosis
Cystic fibrosis is a devastating autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Dehydration of the airway surface liquid and build-up of a thick layer of mucus provide the ideal conditions for bacterial biofilm formation. Common bacterial strains found in these biofilms are notably Pseudomonas aeruginosa and also Staphylococcus aureus and Stenotrophomonas maltophilia among others.
Bacteria within the biofilm are resistant to antibiotic treatment and also evade destruction by the innate and adaptive immune responses. For example, Pseudomonas aeruginosa in biofilms can recognise polymorphonuclear neutrophilic leukocytes (PMNs) attracted to the site of infection and communicate to other bacteria in the biofilm via the quorum sensing signalling system to tell them to up-regulate expression of virulence determinants such as rhamnolipids. Inter-species interaction of bacteria within the biofilm may facilitate microcolony formation. Furthermore, enzymes such as cathepsin produced by Pseudomonas aeruginosa can destroy the innate immune response protein lactoferrin, which is inhibitory of biofilm formation. Biofilm bacteria can also contribute to destructive inflammatory responses by components of the innate immune system. For example, biofilm-forming Pseudomonas aeruginosa lipopolysaccharide modifications compared to their planktonic counterparts that contribute to increased formation of inflammatory mediators such as IL-6 and TNF by human monocytes.
The multi-drug resistance of bacteria in biofilms and their evasion of the immune system have necessitated searches for novel treatments for cystic fibrosis. Current research is exploring a number of avenues. One promising strategy involves use of both natural and artificially designed -helical antimicrobial peptides. Some promising results have been obtained on reduction of viability of Pseudomonas aeruginosa biofilms compared to the antibiotic Tobramycin, which is typically used in CF patients. Other possibilities include targeting the bacterial surface polysaccharide poly-β-(1-6)-N-acetyl-glucosamine (PNAG), which mediates biofilm formation by some bacterial species such as the Burkholderia cepacia complex. The endogenous cationic antibacterial peptides (CAPs) are another potential model for possible therapies, for example based on the cationic corticosteroid disubstituted dexamethasone-spermine (D2S). Genetically engineered alginate lyase enzymes, for example conjugated to PEG are another suggested therapy, while use of ginseng has been shown to enhance phagocytosis of P. aeruginosa PAO1 strain by airway phagocytes. Cystic fibrosis patients and their families may hope to eventually benefit from the fruits of this research to try to find an answer to the problem of multidrug resistance in CF biofilms.
Sources
Pompilio A, Crocetta V, Scocchi M, Pomponio S, Di Vincenzo V, Mardirossian M, Gherardi G, Fiscarelli E, Dicuonzo G, Gennaro R, Di Bonaventura G. BMC Microbiol. 2012 Jul 23; 12:145. 2180-12-145. Potential novel therapeutic strategies in cystic fibrosis: antimicrobial and anti-biofilm activity of natural and designed α-helical peptides against Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia.
Skurnik D, Davis MR Jr, Benedetti D, Moravec KL, Cywes-Bentley C, Roux D, Traficante DC, Walsh RL, Maira-Litràn T, Cassidy SK, Hermos CR, Martin TR, Thakkallapalli EL, Vargas SO, McAdam AJ, Lieberman TD, Kishony R, Lipuma JJ, Pier GB, Goldberg JB, Priebe GP. J Infect Dis. 2012 Jun; 205(11):1709-18. Epub 2012 Mar 23.Targeting pan-resistant bacteria with antibodies to a broadly conserved surface polysaccharide expressed during infection.
Yang L, Liu Y, Markussen T, Høiby N, Tolker-Nielsen T, Molin S. FEMS Immunol Med Microbiol. 2011 Aug;62 (3):339-47. 2011.00820.x. Epub 2011 Jun 14.Pattern differentiation in co-culture biofilms formed by Staphylococcus aureus and Pseudomonas aeruginosa.
Høiby N, Ciofu O, Johansen HK, Song ZJ, Moser C, Jensen PØ, Molin S, Givskov M, Tolker-Nielsen T, Bjarnsholt T. Int J Oral Sci. 2011 Apr;3(2):55-65.The clinical impact of bacterial biofilms.
Lamppa JW, Ackerman ME, Lai JI, Scanlon TC, Griswold KE. PLoS One. 2011 Feb 14;6(2):e17042. Genetically engineered alginate lyase-PEG conjugates exhibit enhanced catalytic function and reduced immunoreactivity.
Wu H, Lee B, Yang L, Wang H, Givskov M, Molin S, Høiby N, Song Z. FEMS Immunol Med Microbiol. 2011 Jun;62(1):49-56. Epub 2011 Mar 7. Effects of ginseng on Pseudomonas aeruginosa motility and biofilm formation.
Høiby N, Ciofu O, Bjarnsholt T. Future Microbiol. 2010 Nov;5(11):1663-74. Pseudomonas aeruginosa biofilms in cystic fibrosis.
Williams BJ, Dehnbostel J, Blackwell TS. Respirology. 2010 Oct;15(7):1037-56. Epub 2010 Aug 16.Pseudomonas aeruginosa: host defence in lung diseases.
Bucki R, Leszczynska K, Byfield FJ, Fein DE, Won E, Cruz K, Namiot A, Kulakowska A, Namiot Z, Savage PB, Diamond SL, Janmey PA. Antimicrob Agents Chemother. 2010 Jun;54(6):2525-33. Epub 2010 Mar 22. Combined antibacterial and anti-inflammatory activity of a cationic disubstituted dexamethasone-spermine conjugate.
Ciornei CD, Novikov A, Beloin C, Fitting C, Caroff M, Ghigo JM, Cavaillon JM, Adib-Conquy M. Innate Immun. 2010 Oct;16(5):288-301. Epub 2009 Aug 26. Biofilm-forming Pseudomonas aeruginosa bacteria undergo lipopolysaccharide structural modifications and induce enhanced inflammatory cytokine response in human monocytes.
Alhede M, Bjarnsholt T, Jensen PØ, Phipps RK, Moser C, Christophersen L, Christensen LD, van Gennip M, Parsek M, Høiby N, Rasmussen TB, Givskov M. Microbiology. 2009 Nov;155(Pt 11):3500-8. Epub 2009 Jul 30. Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytes.
Buchanan PJ, Ernst RK, Elborn JS, Schock B. Biochem Soc Trans. 2009 Aug;37(Pt 4):863-7. Role of CFTR, Pseudomonas aeruginosa and Toll-like receptors in cystic fibrosis lung inflammation.
Rogan MP, Taggart CC, Greene CM, Murphy PG, O'Neill SJ, McElvaney NG. J Infect Dis. 2004 Oct 1;190(7):1245-53. Epub 2004 Aug 26. Loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity in patients with cystic fibrosis.
Cystic fibrosis is a devastating autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Dehydration of the airway surface liquid and build-up of a thick layer of mucus provide the ideal conditions for bacterial biofilm formation. Common bacterial strains found in these biofilms are notably Pseudomonas aeruginosa and also Staphylococcus aureus and Stenotrophomonas maltophilia among others.
Bacteria within the biofilm are resistant to antibiotic treatment and also evade destruction by the innate and adaptive immune responses. For example, Pseudomonas aeruginosa in biofilms can recognise polymorphonuclear neutrophilic leukocytes (PMNs) attracted to the site of infection and communicate to other bacteria in the biofilm via the quorum sensing signalling system to tell them to up-regulate expression of virulence determinants such as rhamnolipids. Inter-species interaction of bacteria within the biofilm may facilitate microcolony formation. Furthermore, enzymes such as cathepsin produced by Pseudomonas aeruginosa can destroy the innate immune response protein lactoferrin, which is inhibitory of biofilm formation. Biofilm bacteria can also contribute to destructive inflammatory responses by components of the innate immune system. For example, biofilm-forming Pseudomonas aeruginosa lipopolysaccharide modifications compared to their planktonic counterparts that contribute to increased formation of inflammatory mediators such as IL-6 and TNF by human monocytes.
The multi-drug resistance of bacteria in biofilms and their evasion of the immune system have necessitated searches for novel treatments for cystic fibrosis. Current research is exploring a number of avenues. One promising strategy involves use of both natural and artificially designed -helical antimicrobial peptides. Some promising results have been obtained on reduction of viability of Pseudomonas aeruginosa biofilms compared to the antibiotic Tobramycin, which is typically used in CF patients. Other possibilities include targeting the bacterial surface polysaccharide poly-β-(1-6)-N-acetyl-glucosamine (PNAG), which mediates biofilm formation by some bacterial species such as the Burkholderia cepacia complex. The endogenous cationic antibacterial peptides (CAPs) are another potential model for possible therapies, for example based on the cationic corticosteroid disubstituted dexamethasone-spermine (D2S). Genetically engineered alginate lyase enzymes, for example conjugated to PEG are another suggested therapy, while use of ginseng has been shown to enhance phagocytosis of P. aeruginosa PAO1 strain by airway phagocytes. Cystic fibrosis patients and their families may hope to eventually benefit from the fruits of this research to try to find an answer to the problem of multidrug resistance in CF biofilms.
Sources
Pompilio A, Crocetta V, Scocchi M, Pomponio S, Di Vincenzo V, Mardirossian M, Gherardi G, Fiscarelli E, Dicuonzo G, Gennaro R, Di Bonaventura G. BMC Microbiol. 2012 Jul 23; 12:145. 2180-12-145. Potential novel therapeutic strategies in cystic fibrosis: antimicrobial and anti-biofilm activity of natural and designed α-helical peptides against Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia.
Skurnik D, Davis MR Jr, Benedetti D, Moravec KL, Cywes-Bentley C, Roux D, Traficante DC, Walsh RL, Maira-Litràn T, Cassidy SK, Hermos CR, Martin TR, Thakkallapalli EL, Vargas SO, McAdam AJ, Lieberman TD, Kishony R, Lipuma JJ, Pier GB, Goldberg JB, Priebe GP. J Infect Dis. 2012 Jun; 205(11):1709-18. Epub 2012 Mar 23.Targeting pan-resistant bacteria with antibodies to a broadly conserved surface polysaccharide expressed during infection.
Yang L, Liu Y, Markussen T, Høiby N, Tolker-Nielsen T, Molin S. FEMS Immunol Med Microbiol. 2011 Aug;62 (3):339-47. 2011.00820.x. Epub 2011 Jun 14.Pattern differentiation in co-culture biofilms formed by Staphylococcus aureus and Pseudomonas aeruginosa.
Høiby N, Ciofu O, Johansen HK, Song ZJ, Moser C, Jensen PØ, Molin S, Givskov M, Tolker-Nielsen T, Bjarnsholt T. Int J Oral Sci. 2011 Apr;3(2):55-65.The clinical impact of bacterial biofilms.
Lamppa JW, Ackerman ME, Lai JI, Scanlon TC, Griswold KE. PLoS One. 2011 Feb 14;6(2):e17042. Genetically engineered alginate lyase-PEG conjugates exhibit enhanced catalytic function and reduced immunoreactivity.
Wu H, Lee B, Yang L, Wang H, Givskov M, Molin S, Høiby N, Song Z. FEMS Immunol Med Microbiol. 2011 Jun;62(1):49-56. Epub 2011 Mar 7. Effects of ginseng on Pseudomonas aeruginosa motility and biofilm formation.
Høiby N, Ciofu O, Bjarnsholt T. Future Microbiol. 2010 Nov;5(11):1663-74. Pseudomonas aeruginosa biofilms in cystic fibrosis.
Williams BJ, Dehnbostel J, Blackwell TS. Respirology. 2010 Oct;15(7):1037-56. Epub 2010 Aug 16.Pseudomonas aeruginosa: host defence in lung diseases.
Bucki R, Leszczynska K, Byfield FJ, Fein DE, Won E, Cruz K, Namiot A, Kulakowska A, Namiot Z, Savage PB, Diamond SL, Janmey PA. Antimicrob Agents Chemother. 2010 Jun;54(6):2525-33. Epub 2010 Mar 22. Combined antibacterial and anti-inflammatory activity of a cationic disubstituted dexamethasone-spermine conjugate.
Ciornei CD, Novikov A, Beloin C, Fitting C, Caroff M, Ghigo JM, Cavaillon JM, Adib-Conquy M. Innate Immun. 2010 Oct;16(5):288-301. Epub 2009 Aug 26. Biofilm-forming Pseudomonas aeruginosa bacteria undergo lipopolysaccharide structural modifications and induce enhanced inflammatory cytokine response in human monocytes.
Alhede M, Bjarnsholt T, Jensen PØ, Phipps RK, Moser C, Christophersen L, Christensen LD, van Gennip M, Parsek M, Høiby N, Rasmussen TB, Givskov M. Microbiology. 2009 Nov;155(Pt 11):3500-8. Epub 2009 Jul 30. Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytes.
Buchanan PJ, Ernst RK, Elborn JS, Schock B. Biochem Soc Trans. 2009 Aug;37(Pt 4):863-7. Role of CFTR, Pseudomonas aeruginosa and Toll-like receptors in cystic fibrosis lung inflammation.
Rogan MP, Taggart CC, Greene CM, Murphy PG, O'Neill SJ, McElvaney NG. J Infect Dis. 2004 Oct 1;190(7):1245-53. Epub 2004 Aug 26. Loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity in patients with cystic fibrosis.
![[+]](https://www.biotechnologyforums.com/images/netpen-pro/collapse_collapsed.png)