Analytical and Bioanalytical Chemistry

, Volume 407, Issue 27, pp 8233–8241 | Cite as

Discrimination of urinary tract infection pathogens by means of their growth profiles using surface enhanced Raman scattering

  • Ertug Avci
  • Nur Selin Kaya
  • Gizem Ucankus
  • Mustafa CulhaEmail author
Research Paper
Part of the following topical collections:
  1. Nanospectroscopy


Urinary tract infection (UTI) is a widespread infection and affects millions of people around the globe. The gold standard for identification of microorganisms causing infection is urine culture. However, current methods require at least 24 h for the results. In clinical settings, identification and discrimination of bacteria with less time-consuming and cheaper methods are highly desired. In recent years, the power of surface-enhanced Raman scattering (SERS) for fast identification of bacteria and biomolecules has been demonstrated. In this study, we show discrimination of urinary tract infection causative pathogens within 1 h of incubation using principal component analysis (PCA) of SERS spectra of seven different UTI causative bacterial species. In addition, we showed differentiation of them at their different growth phases. We also analyzed origins of bacterial SERS spectra and demonstrated the highly dynamic structure of the bacteria cell wall during their growth.

Graphical Abstract

Collection of bacteria from urine sample, and their discrimination using their SERS spectra and multivariate analysis


Urinary tract infection Bacteria Growth phase Surface-enhanced Raman scattering Principal component analysis 



The authors gratefully acknowledge the financial support of Yeditepe University and Technological Research Council of Turkey (TUBITAK) for this study. The authors also acknowledge the contribution Associate Prof. Çağatay Acuner and Prof. Dr. Gülden Yılmaz of Yeditepe University Medical School for providing some of the bacteria species.

Conflict of interest

The authors declare that there is no conflict of interest.

Supplementary material

216_2015_8950_MOESM1_ESM.pdf (3.3 mb)
ESM 1 (PDF 3.28 MB)


  1. 1.
    Dielubanza EJ, Schaeffer AJ (2011) Urinary tract infections in women. Med Clin North Am 95:27–41CrossRefGoogle Scholar
  2. 2.
    Nicolle LE (2009) Urinary tract infections in the elderly. Clin Geriatr Med 25:423–436CrossRefGoogle Scholar
  3. 3.
    Barber AE, Norton JP, Spivak AM, Mulvey MA (2013) Urinary tract infections: current and emerging management strategies. Clin Infect Dis 57:719–724CrossRefGoogle Scholar
  4. 4.
    Schmiemann G, Kniehl E, Gebhardt K, Matejczyk MM, Hummers-Pradier E (2010) The diagnosis of urinary tract infection. Dtsch Arztebl Int 107:361–367Google Scholar
  5. 5.
    Pezzlo M (2014) Laboratory diagnosis of urinary tract infections: guidelines, challenges, and innovations. Clin Microbiol Newsl 36:87–93CrossRefGoogle Scholar
  6. 6.
    Lehmann LE, Hauser S, Malinka T, Klaschik S, Weber SU, Schewe J-C, Stüber F, Book M (2011) Rapid qualitative urinary tract infection pathogen identification by SeptiFast® real-time PCR. PLoS One 6, e17146CrossRefGoogle Scholar
  7. 7.
    Liao JC, Mastali M, Gau V, Suchard MA, Møller AK, Bruckner DA, Babbitt JT, Li Y, Gornbein J, Landaw EM, McCabe ER, Churchill BM, Haake DA (2006) Use of electrochemical DNA biosensors for rapid molecular identification of uropathogens in clinical urine specimens. J Clin Microbiol 44:561–570CrossRefGoogle Scholar
  8. 8.
    Ferreira L, Sánchez-Juanes F, Muñoz-Bellido JL, González-Buitrago JM (2011) Rapid method for direct identification of bacteria in urine and blood culture samples by matrix-assisted laser desorption ionization time-of-flight mass spectrometry: intact cell vs. extraction method. Clin Microbiol Infect 17:1007–1012CrossRefGoogle Scholar
  9. 9.
    Gupta A, Dwivedi M, Mahdi AA, Khetrapal CL, Bhandari MJ (2012) Broad identification of bacterial type in urinary tract infection using 1H NMR spectroscopy. Proteome Res 11:1844–1854CrossRefGoogle Scholar
  10. 10.
    Pahlow S, Meisel S, Cialla-May D, Weber K, Rösch P, Popp J (2015) Isolation and identification of bacteria by means of Raman spectroscopy. Adv Drug Deliv Rev. doi: 10.1016/j.addr.2015.04.006 Google Scholar
  11. 11.
    Neugebauer U, Schmid U, Baumann K, Ziebuhr W, Kozitskaya S, Deckert V, Schmitt M, Popp J (2007) Towards a detailed understanding of bacterial metabolism-spectroscopic characterization of Staphylococcus epidermidis. ChemPhysChem 8:124–137CrossRefGoogle Scholar
  12. 12.
    Kann B, Offerhaus HL, Windbergs M, Otto C (2015) Raman microscopy for cellular investigations-from single cell imaging to drug carrier uptake visualization. Adv Drug Deliv Rev. doi: 10.1016/j.addr.2015.02.006 Google Scholar
  13. 13.
    Bispo JAM, De Sousa Vieira EE, Silveira L, Fernandes AB (2013) Correlating the amount of urea, creatinine, and glucose in urine from patients with diabetes mellitus and hypertension with the risk of developing renal lesions by means of Raman spectroscopy and principal component analysis. J Biomed Opt 8:087004CrossRefGoogle Scholar
  14. 14.
    Kim ZH (2014) Single-molecule surface-enhanced Raman scattering: current status and future perspective. Front Phys 9:25–30CrossRefGoogle Scholar
  15. 15.
    Zhou H, Yang Y, Ivleva NP, Mircescu NE, Niessner R, Haisch C (2014) SERS detection of bacteria in water by in situ coating with Ag nanoparticles. Anal Chem 86:1525–1533CrossRefGoogle Scholar
  16. 16.
    Kahraman M, Keseroglu K, Culha M (2011) On sample preparation for surface-enhanced Raman scattering (SERS) of bacteria and the source of spectral features of the spectra. Appl Spectrosc 65:500–506CrossRefGoogle Scholar
  17. 17.
    Culha M, Kahraman M, Çam D, Sayın I, Keseroğlu K (2010) Rapid identification of bacteria and yeast using surface-enhanced Raman scattering. Surf Interface Anal 42:462–465CrossRefGoogle Scholar
  18. 18.
    Cam D, Keseroğlu K, Kahraman M, Sahin F, Culha M (2010) Multiplex identification of bacteria in bacterial mixtures with surface-enhanced Raman scattering. J Raman Spectrosc 41:484–489CrossRefGoogle Scholar
  19. 19.
    Kahraman M, Zamaleeva AI, Fakhrullin RF, Culha M (2009) Layer-by-layer coating of bacteria with noble metal nanoparticles for surface-enhanced Raman scattering. Anal Bioanal Chem 395:2559–2567CrossRefGoogle Scholar
  20. 20.
    Liu TT, Lin YH, Hung CS, Liu TJ, Chen Y, Huang YC, Tsai TH, Wang HH, Wang DW, Wang JK, Wang YL, Lin CH (2009) A high speed detection platform based on surface-enhanced Raman scattering for monitoring antibiotic-induced chemical changes in bacteria cell wall. PLoS One 4, e5470CrossRefGoogle Scholar
  21. 21.
    Kahraman M, Yazici MM, Sahin F, Çulha M (2008) Convective assembly of bacteria for surface-enhanced Raman scattering. Langmuir 24:894–901CrossRefGoogle Scholar
  22. 22.
    Mert S, Çulha M (2014) Surface-enhanced Raman scattering-based detection of cancerous renal cells. Appl Spectrosc 68:617–624CrossRefGoogle Scholar
  23. 23.
    Mert S, Özbek E, Ötünçtemur A, Çulha M (2015) Kidney tumor staging using surface-enhanced Raman scattering. J Biomed Opt 20:047002CrossRefGoogle Scholar
  24. 24.
    Avci E, Culha M (2014) Influence of protein size on surface-enhanced Raman scattering (SERS) spectra in binary protein mixtures. Appl Spectrosc 68:890–899CrossRefGoogle Scholar
  25. 25.
    Premasiri WR, Lemler P, Chen Y, Gebregziabher Y, Ziegler LD (2014) SERS analysis of bacteria, human blood and cancer cells: a metabolomic and diagnostic tool. In: Ozaki Y, Kneipp K, Aroca R (eds) Frontiers of surface-enhanced Raman scattering: single-nanoparticles and single cells, 1st edn. Wiley, Chichester, pp 255–282Google Scholar
  26. 26.
    Hadjigeorgiou K, Kastanos E, Pitris C (2013) Multi-bacteria multi-antibiotic testing using surface enhanced Raman spectroscopy (SERS) for urinary tract infection (UTI) diagnosis. Proc SPIE 8798:87980LCrossRefGoogle Scholar
  27. 27.
    Hadjigeorgiou K, Kastanos E, Pitris C (2013) Urinary tract infection (UTI) multi-bacteria multi-antibiotic testing using surface enhanced Raman spectroscopy (SERS). Proc SPIE 8591:85910BCrossRefGoogle Scholar
  28. 28.
    Hadjigeorgiou K, Kastanos E, Kyriakides A, Pitris C (2012) Complete urinary tract infection (UTI) diagnosis and antibiogram using surface enhanced Raman spectroscopy (SERS). Proc SPIE 8229:82290DCrossRefGoogle Scholar
  29. 29.
    Kastanos E, Kyriakides A, Hadjigeorgiou K, Pitris C (2010) A novel method for urinary tract infection diagnosis and antibiogram using Raman spectroscopy. J Raman Spectrosc 41:958–963CrossRefGoogle Scholar
  30. 30.
    Jarvis RM, Goodacre R (2004) Discrimination of bacteria using surface-enhanced Raman spectroscopy. Anal Chem 76:40–47CrossRefGoogle Scholar
  31. 31.
    Mircescu NE, Zhou H, Leopold N, Chiş V, Ivleva NP, Niessner R, Wieser A, Haisch C (2014) Towards a receptor-free immobilization and SERS detection of urinary tract infections causative pathogens. Anal Bioanal Chem 406:3051–3058CrossRefGoogle Scholar
  32. 32.
    Turner RD, Vollmer W, Foster SJ (2014) Different walls for rods and balls: the diversity of peptidoglycan. Mol Microbiol 91:862–874CrossRefGoogle Scholar
  33. 33.
    Johnson JW, Fisher JF, Mobashery S (2013) Bacterial cell-wall recycling. Ann N Y Acad Sci 1277:54–75CrossRefGoogle Scholar
  34. 34.
    Typas A, Banzhaf M, Gross CA, Vollmer W (2011) From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat Rev Microbiol 10:123–136Google Scholar
  35. 35.
    Carlson HK, Iavarone AT, Gorur A, Yeo BS, Tran R, Melnyk RA, Mathies RA, Auer M, Coates JD (2012) Surface multiheme c-type cytochromes from Thermincola potens and implications for respiratory metal reduction by Gram-positive bacteria. Proc Natl Acad Sci U S A 109:1702–1707CrossRefGoogle Scholar
  36. 36.
    Biju V, Pan D, Gorby YA, Fredrickson J, McLean J, Saffarini D, Lu HP (2007) Combined spectroscopic and topographic characterization of nanoscale domains and their distributions of a redox protein on bacterial cell surfaces. Langmuir 23:1333–1338CrossRefGoogle Scholar
  37. 37.
    Leopold N, Lendl B (2003) A new method for fast preparation of highly Surface-Enhanced Raman Scattering (SERS) active silver colloids at room temperature by reduction of silver nitrate with hydroxylamine hydrochloride. J Phys Chem B 107:5723–5727CrossRefGoogle Scholar
  38. 38.
    Premasiri WR, Gebregziabher Y, Ziegler LD (2011) On the difference between surface-enhanced raman scattering (SERS) spectra of cell growth media and whole bacterial cells. Appl Spectrosc 65:493–499CrossRefGoogle Scholar
  39. 39.
    Premasiri WR, Moir DT, Klempner MS, Krieger N, Jones G 2nd, Ziegler LD (2005) Characterization of the surface enhanced Raman scattering (SERS) of bacteria. J Phys Chem B 109:312–320CrossRefGoogle Scholar
  40. 40.
    Osorio-Román IO, Aroca RF, Astudillo J, Matsuhiro B, Vásquez C, Pérez JM (2010) Characterization of bacteria using its O-antigen with surface-enhanced Raman scattering. Analyst 135:1997–2001CrossRefGoogle Scholar
  41. 41.
    Efrima S, Zeiri L (2009) Understanding SERS of bacteria. J Raman Spectrosc 40:277–288CrossRefGoogle Scholar
  42. 42.
    Zeiri L, Efrima S (2006) Surface-Enhanced Raman Scattering (SERS) of microorganisms. Isr J Chem 46:337–346CrossRefGoogle Scholar
  43. 43.
    Zeiri L, Bronk BV, Shabtai Y, Eichler J, Efrima S (2004) Surface-enhanced Raman spectroscopy as a tool for probing specific biochemical components in bacteria. Appl Spectrosc 58:33–40CrossRefGoogle Scholar
  44. 44.
    Kazanci M, Schulte JP, Douglas C, Fratzl P, Pink D, Smith-Palmer T (2009) Tuning the surface-enhanced Raman scattering effect to different molecular groups by switching the silver colloid solution pH. Appl Spectrosc 63:214–223CrossRefGoogle Scholar
  45. 45.
    Knauer M, Ivleva NP, Liu X, Niessner R, Haisch C (2010) Surface-enhanced Raman scattering-based label-free microarray readout for the detection of microorganisms. Anal Chem 82:2766–2772CrossRefGoogle Scholar
  46. 46.
    Ivleva NP, Wagner M, Szkola A, Horn H, Niessner R, Haisch C (2010) Label-free in situ SERS imaging of biofilms. J Phys Chem B 114:10184–10194CrossRefGoogle Scholar
  47. 47.
    Kahraman M, Sur I, Culha M (2010) Label-free detection of proteins from self-assembled protein-silver nanoparticle structures using surface-enhanced Raman scattering. Anal Chem 82:7596–7602CrossRefGoogle Scholar
  48. 48.
    Vinogradova E, Tlahuice-Flores A, Velazquez-Salazar JJ, Larios-Rodriguez E, Jose-Yacaman M (2014) Surface-enhanced Raman scattering of N-acetylneuraminic acid on silver nanoparticle surface. J Raman Spectrosc 45:730–735CrossRefGoogle Scholar
  49. 49.
    Huang R, Yang H-T, Cui L, Wu D-Y, Ren B, Tian Z-Q (2013) Structural and charge sensitivity of surface-enhanced Raman spectroscopy of adenine on silver surface: a quantum chemical study. J Phys Chem B 117:23730–23737Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Ertug Avci
    • 1
  • Nur Selin Kaya
    • 1
  • Gizem Ucankus
    • 1
  • Mustafa Culha
    • 1
    Email author
  1. 1.Department of Genetics and Bioengineering, Faculty of Engineering and ArchitectureYeditepe UniversityIstanbulTurkey

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