Effect of Human Insulin on the Formation of Catheter-Associated E. coli Biofilms


Biofilm formation is essential for the survival and growth of Escherichia coli in catheter-associated infections. Individuals with type 2 diabetes mellitus can excrete insulin and/or glucose in their urine. This population also has an increased incidence of urinary tract infections. The focus of this study was to determine if the composition of Foley catheter material affects biofilm formation by E. coli in a model system for type 2 diabetes mellitus. Rubber (lubricious-coated), silicon-coated, silver-coated and nitrofurazone-coated catheter segments (5 mm; n = 6) were tested. Catheter segments were added to E. coli ATCC25922 (104 CFU/ml, final concentration) in artificial urine alone, or with insulin (40 μU/ml) and/or glucose (0.1%). After incubation (18 h, 37?C, in air and anaerobically) the level of catheter-associated biofilm was determined by crystal violet staining (Abs550nm). Statistical analysis was done by ANOVA with post-hoc analysis (Tukey). Neither nitrofurazone-coated nor silver-coated catheters supported the formation of E. coli biofilm, regardless of growth condition tested. In contrast, under aerobic biofilm formation on silicon catheters was significantly higher (p < 0.05) than that on sterile catheter alone. In addition, glucose with insulin induced significantly more biofilm (p < 0.05) than E. coli controls. Biofilm formation was also significantly increased (p < 0.05) under anaerobic conditions on lubricious-coated rubber catheters as compared to sterile catheters. These results may aid in the development of a catheter material that can prevent biofilm formation, or alternatively guide choice of catheter material for individuals shedding insulin in their urine.

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Plotkin, B. , Wu, Z. , Ward, K. , Nadella, S. , Green, J. and Rumnani, B. (2014) Effect of Human Insulin on the Formation of Catheter-Associated E. coli Biofilms. Open Journal of Urology, 4, 49-56. doi: 10.4236/oju.2014.45009.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Brosnahan, J., Jull, A. and Tracy, C. (2004) Types of Urethral Catheters for Management of Short-Term Voiding Problems in Hospitalized Adults. Cochrane Database System Review, 16, Article ID: CD004013.
[2] Hazelett, S., Tsai, M., Gareri, M. and Allen, K. (2006) The Association between Indwelling Urinary Catheter Use in the Elderly and Urinary Tract Infection in Acute Care. BMC Geriatrics, 6, 15-23. http://dx.doi.org/10.1186/1471-2318-6-15
[3] Jacobsen, S., Stickler, D., Mobley, H. and Shirtliff, M. (2008) Complicated Catheter-Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis. Clinical Microbiology Reviews, 21, 26-59. http://dx.doi.org/10.1128/CMR.00019-07
[4] Leuck, A.-M., Wright, D., Ellingson, L., Kraemer, L., Kuskowski, M.A. and Johnson, J.R. (2012) Complications of Foley Catheters—Is Infection the Greatest Risk? The Journal of Urology, 187, 1662-1666. http://dx.doi.org/10.1016/j.juro.2011.12.113
[5] Nicolle, L. (2005) Catheter-Related Urinary Tract Infection. Drugs Aging, 22, 627-639.
[6] Saint, S. and Chenoweth, C. (2003) Biofilms and Catheter-Associated Urinary Tract Infections. Infectious Disease Clinics of North America, 17, 411-432. http://dx.doi.org/10.1016/S0891-5520(03)00011-4
[7] Muller, L., Gorter, K.J., Hak, E., Goudzwaard, W.L., Schellevis, F.G., Hoepelman, A.I.M. and Rutten, G. (2005) Increased Risk of Common Infections in Patients with Type 1 and Type 2 Diabetes Mellitus. Clinical Infectious Diseases, 41, 281-288. http://dx.doi.org/10.1086/431587
[8] Constan, L., Mako, M., Juhn, D. and Rubenstein, A.H. (1975) The Excretion of Proinsulin and Insulin in Urine. Diabetologia, 11, 119-123. http://dx.doi.org/10.1007/BF00429834
[9] Geerlings, S.E., Brouwer, E.C., Gaastra, W., Verhoef, J. and Hoepelman, A.I.M. (1999) Effect of Glucose and pH on Uropathogenic and Non-Uropathogenic Escherichia coli: Studies with Urine from Diabetic and Non-Diabetic Individuals. Journal of Medical Microbiology, 48, 535-539.
[10] Geerlings, S.E., Meiland, R. and Hoepelman, A.I.M. (2002) Pathogenesis of Bacteriuria in Women with Diabetes Mellitus. International Journal of Antimicrobial Agents, 19, 539-545.
[11] Hanabusa, T., Oki, C., Nakano, Y., Okai, K., Nishi, M., Sasaki, H., Sanke, T. and Nanjo, K. (2001) The Renal Metabolism of Insulin: Urinary Insulin Excretion in Patients with Mutant Insulin Syndrome (Insulin Wakayama). Metabolism, 50, 863-867. http://dx.doi.org/10.1053/meta.2001.24885
[12] Rabkin, R., Ryan, M. and Duckworth, W. (1984) The Renal Metabolism of Insulin. Diabetologia, 27, 351-357. http://dx.doi.org/10.1007/BF00304849
[13] Rubenstein, A.H., Lowy, C., Welborn, T.A. and Fraser, T.R. (1967) Urine Insulin in Normal Subjects. Metabolism, 16, 234-244. http://dx.doi.org/10.1016/0026-0495(67)90172-2
[14] Trayner, I.M., Welborn, T.A., Rubenstein, A. and Fraser, T.R. (1967) Serum and Urine Insulin in Late Pregnancy and in a Few Pregnant Latent Diabetics. Journal of Endocrinology, 37, 443-453. http://dx.doi.org/10.1677/joe.0.0370443
[15] Wang, M.C., Tseng, C.C., Wu, A.B., Lin, W.H., Teng, C.H., Yan, J.J. and Wu, J.J. (2013) Bacterial Characteristics and Glycemic Control in Diabetic Patients with Escherichia coli Urinary Tract Infection. Journal of Microbiology Immunology and Infection, 46, 24-29.
[16] Foxman, B. (2002) Epidemiology of Urinary Tract Infections: Incidence, Morbidity, and Economic Costs. American Journal of Medicine, 113, S5-S13. http://dx.doi.org/10.1016/S0002-9343(02)01054-9
[17] Geerlings, S., Brouwer, E., Gaastra, W., Stolk, R., Diepersloot, R. and Hoepelman, A. (2001) Virulence Factors of Escherichia coli Isolated from Urine of Diabetic Women with Asymptomatic Bacteriuria: Correlation with Clinical Characteristics. Antonie van Leeuwenhoek, 80, 119-127.
[18] Geerlings, S.E., Meiland, R. and Hoepelman, A.I. (2002) Pathogenesis of Bacteriuria in Women with diabetes Mellitus. International Journal of Antimicrobial Agents, 19, 539-545.
[19] Johnson, J. (1991) Virulence Factors in Escherichia coli Urinary Tract Infection. Clinical Microbiology Reviews, 4, 80-128.
[20] Donlan, R. (2001) Biofilm Formation: A Clinically Relevant Microbiological Process. Clinical Infectious Diseases, 33, 1387-1392. http://dx.doi.org/10.1086/322972
[21] Gilbert, P., Maira-Litran, T., McBain, A.J., Rickard, A.H. and Whyte, F.W. (2002) The Physiology and Collective Recalcitrance of Microbial Biofilm Communities. Advances in Microbial Physiology, 46, 202-256. http://dx.doi.org/10.1016/S0065-2911(02)46005-5
[22] Goller, C. and Romeo, T. (2008) Environmental Influences on Biofilm Development. Current Topics in Microbiology and Immunology, 322, 37-66. http://dx.doi.org/10.1007/978-3-540-75418-3_3
[23] Hall-Stoodley, L., Costerton, J. and Stoodley, P. (2004) Bacterial Biofilms: From the Natural Environment to Infectious Diseases. Nature Reviews Microbiology, 2, 95-108.
[24] Plotkin, B.J. and Viselli, S.M. (2000) Effect of Insulin on Microbial Growth. Current Microbiology, 41, 60-64. http://dx.doi.org/10.1007/s002840010092
[25] Klosowska, K. and Plotkin, B. (2006) Human Insulin Modulation of Escherichia coli Adherence and Chemotaxis. American Journal of Infectious Diseases, 2, 197-200.
[26] Stickler, D. (2008) Bacterial Biofilms in Patients with Indwelling Urinary Catheters. Nature Review Urology, 5, 598-608.
[27] Stickler, D., Morris, N., McLean, R. and Fuqua, C. (1998) Biofilms on Indwelling Urethral Catheters Produce Quorum-Sensing Signal Molecules in Situ and in Vitro. Applied and Environmental Microbiology, 64, 3486-3490.
[28] Cavalieri, S.J., Bohach, G.A. and Snyder, I.S. (1984) Escherichia coli Alpha-Hemolysin: Characteristics and Probable Role in Pathogenicity. Microbiological Reviews, 48, 326-343.
[29] Castonguay, M., van der Schaaf, S., Koester, W., Krooneman, J., van der Meer, W., Harmsen, H. and Landini, P. (2006) Biofilm Formation by Escherichia coli Is Stimulated by Synergistic Interactions and Co-Adhesion Mechanisms with Adherence-Proficient Bacteria. Research in Microbiology, 157, 471-478. http://dx.doi.org/10.1016/j.resmic.2005.10.003
[30] Maidhof, H., Reinicke, B., Blumel, P., Berger-Bachi, B. and Labischinski, H. (1991) femA, Which Encodes a Factor for Expression of Methicillin Resistance, Affects Glycine Content of Peptidoglycan in Methicillin Resistant and Methicillin Susceptible Staphylococcus aureus Strains. Journal of Bacteriology, 173, 3507-3513.
[31] Ostrowska, K., Strzelczyk, A., Rozalski, A. and Staczek, P. (2013) Bacterial Biofilm as a Cause of Urinary Tract Infection—Pathogens, Methods of Prevention and Eradication. Post?py Higieny i Medycyny Do?wiadczalnej, 67, 1027-1033.
[32] Pavan, H.V., Akshatha, K.N. and Murthy, M.S. (2013) Catheter-Associated Urinary Tract Infections and Prevention by Bacterial Interference: A Review. Reviews in Medical Microbiology, 24, 98-103. http://dx.doi.org/10.1097/MRM.0b013e328364ff4d

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