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Journal of Clinical Microbiology, December 2005, p. 6221-6222, Vol. 43, No. 12
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.12.6221-6222.2005

LETTER TO THE EDITOR

Virulence Factors in Escherichia coli


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LETTER
 
Drews et al. convincingly demonstrate a lower prevalence of beta-hemolysis and papEF among nalidixic acid- or ciprofloxacin-resistant Escherichia coli urine isolates from their locale, compared with susceptible isolates (1). However, several of the authors' assumptions and conclusions deserve comment. First, in studies not cited by Drews et al., similar (and more extensive) associations have been demonstrated among extraintestinal E. coli isolates for ciprofloxacin resistance, nalidixic acid resistance, and multidrug resistance (3-8). Thus, the present study is confirmatory, rather than adding "a new dimension to previous work." Second, the concept that "fluoroquinolone resistance is linked to loss of beta-hemolysis and papEF" must be strongly challenged. There actually is no evidence that the hemolysin- and pap-negative strains ever had these traits and, consequently, that they have lost them. On the contrary, abundant evidence now indicates that quinolone-resistant and -susceptible E. coli clinical isolates represent two quite distinct populations. Resistant isolates derive predominantly from non-B2 E. coli phylogenetic groups, within which hemolysin and pap are quite uncommon, whereas susceptible isolates tend to be from (virulence factor-rich) phylogenetic group B2 (3-6). Thus, differences in phylogenetic distribution can largely account for observed differences in virulence factor prevalence between resistant and susceptible isolates (3-5). Likewise, experimental data now show that conversion to fluoroquinolone resistance in E. coli is not accompanied by significant loss of virulence genes (2). Finally, it is unclear what proportion of the isolates studied by Drews et al. truly represented "uropathogenic" E. coli, since urine organisms were collected without epidemiological data regarding clinical manifestations (or lack thereof) and underlying host status. Thus, an undefined proportion of the isolates likely represented low-virulence colonizers or opportunists, rather than true pathogens.


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REFERENCES
 
    1
  1. Drews, S. J., S. M. Poutanen, T. Mazulli, A. J. McGeer, A. Sarabia, S. Pong-Porter, Y. Rzayev, B. Willey, K. Green, and D. E. Low. 2005. Decreased prevalence of virulence factors among ciprofloxacin-resistant uropathogenic Escherichia coli isolates. J. Clin. Microbiol. 43:4218-4220.[Abstract/Free Full Text]
  2. 2
  3. Johnson, J. R., B. Johnston, R. Raz, R. Colodner, and M. Kuskowski. 2005. Spontaneous conversion to quinolone and fluoroquinolone resistance among wild-type Escherichia coli isolates in relation to phylogenetic background and virulence genotype. Antimicrob. Agents Chemother. 49:4739-4744.[Abstract/Free Full Text]
  4. 3
  5. Johnson, J. R., M. A. Kuskowski, A. Gajewski, D. F. Sahm, and J. A. Karlowsky. 2004. Virulence characteristics and phylogenetic background of multidrug-resistant and antimicrobial-susceptible clinical isolates of Escherichia coli from across the United States, 2000-2001. J. Infect. Dis. 190:1739-1744.[CrossRef][Medline]
  6. 4
  7. Johnson, J. R., M. A. Kuskowski, T. T. O'Bryan, R. Colodner, and R. Raz. 2005. Virulence genotype and phylogenetic origin in relation to antibiotic resistance profile among Escherichia coli urine sample isolates from Israeli women with acute uncomplicated cystitis. Antimicrob. Agents Chemother. 46:26-31.
  8. 5
  9. Johnson, J. R., M. A. Kuskowski, K. Owens, A. Gajewski, and P. L. Winokur. 2003. Phylogenetic origin and virulence genotype in relation to resistance to fluoroquinolones and/or extended spectrum cephalosporins and cephamycins among Escherichia coli isolates from animals and humans. J. Infect. Dis. 188:759-768.[CrossRef][Medline]
  10. 6
  11. Johnson, J. R., C. Van der Schee, M. A. Kuskowski, W. Goessens, and A. Van Belkum. 2002. Phylogenetic background and virulence profiles of fluoroquinolone-resistant clinical Escherichia coli isolates from The Netherlands. J. Infect. Dis. 186:1852-1856.[CrossRef][Medline]
  12. 7
  13. Kuntaman, K., E. S. Lestari, J. A. Severin, I. M. Kershof, N. M. Mertaniasih, M. Purwanta, U. Hadi, J. R. Johnson, A. van Belkum, and H. A. Verbrugh. 2005. Fluoroquinolone-resistant Escherichia coli, Indonesia. Emerg. Infect. Dis. 11:1363-1369.[Medline]
  14. 8
  15. Martinez-Martinez, L., F. Fernandez, and E. J. Perea. 1999. Relationship between haemolysis production and resistance to fluoroquinolones among clinical isolates of Escherichia coli. J. Antimicrob. Chemother. 43:277-279.[Abstract/Free Full Text]
James R. Johnson
University of Minnesota Department   of Medicine
Infectious Diseases (111F)
Minneapolis VA Medical Center
1 Veterans Drive
Minneapolis, MN 55417
Phone: (612) 467-4185,
Fax: (612) 727-5995,
E-mail: johns007@umn.edu


Authors' Reply


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LETTER 
 
We thank Dr. Johnson for the comments regarding our paper (1) and would like to respond to them in the order they appear.

(i) Dr. Johnson contends that our work is "confirmatory" instead of unique and that if we had been aware of a number of his publications we would not have come to this conclusion. Although we were aware of previous studies making this association, they did not include the patient population that we thought worthy of further study, namely, in- and outpatients with urinary tract infections (UTIs). Several of these studies did not focus on urinary tract isolates of Escherichia coli but instead studied extraintestinal isolates of mixed origin, including urinary tract isolates (3-5, 9). One paper focused on UTIs, and this was specifically in cystitis cases in Israel (2). In contrast, our goal was to study virulence factors in E. coli isolates only from E. coli isolated from urine in both inpatient and outpatient urine isolates, since we know that urinary tract isolates are genetically diverse (6) and that different virulence factors are selected for in different locations of the urinary tract (7).

(ii) Dr. Johnson then argues that we should not be using the word "loss" to describe a difference in the frequency of virulence factors between ciprofloxacin-susceptible and -resistant isolates in both patient populations. We agree that there are several different mechanisms for diversity in the carriage of virulence factors within a population of bacteria. However, in this paper, we are using the mechanisms of loss to discuss the molecular mechanism that might be responsible for this difference.

(iii) Dr. Johnson is concerned that our strains may not truly represent "uropathogenic E. coli" since our study was a retrospective study of all urinary tract isolates, without documentation of the exact clinical correlates. Although we recognize that this is a potential weakness of our study design, the criteria used by our laboratory for identifying and reporting significant organisms in the urinary tract are those recommended and used by College of American Pathologists-accredited laboratories (8).


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REFERENCES 
 
    1
  1. Drews, S. J., S. M. Poutanen, T. Mazzulli, A. J. McGeer, A. Sarabia, S. Pong-Porter, Y. Rzayev, B. Willey, K. Green, and D. E. Low. 2005. Decreased prevalence of virulence factors among ciprofloxacin-resistant uropathogenic Escherichia coli isolates. J. Clin. Microbiol. 43:4218-4220.
  2. 2
  3. Johnson, J. R., M. A. Kuskowski, T. T. O'Bryan, R. Colodner, and R. Raz. 2005. Virulence genotype and phylogenetic origin in relation to antibiotic resistance profile among Escherichia coli urine sample isolates from Israeli women with acute uncomplicated cystitis. Antimicrob. Agents Chemother. 49:26-31.[Abstract/Free Full Text]
  4. 3
  5. Johnson, J. R., M. A. Kuskowski, K. Owens, A. Gajewski, and P. L. Winokur. 2003. Phylogenetic origin and virulence genotype in relation to resistance to fluoroquinolones and/or extended-spectrum cephalosporins and cephamycins among Escherichia coli isolates from animals and humans. J. Infect. Dis. 188:759-768.
  6. 4
  7. Johnson, J. R., C. van der Schee, M. A. Kuskowski, W. Goessens, and A. van Belkum. 2002. Phylogenetic background and virulence profiles of fluoroquinolone-resistant clinical Escherichia coli isolates from The Netherlands. J. Infect. Dis. 186:1852-1856.
  8. 5
  9. Martinez-Martinez, L., F. Fernandez, and E. J. Perea. 1999. Relationship between haemolysis production and resistance to fluoroquinolones among clinical isolates of Escherichia coli. J. Antimicrob. Chemother. 43:277-279.
  10. 6
  11. Perrin, M., P. Y. Donnio, C. Heurtin-Lecorre, M. F. Travert, and J. L. Avril. 1999. Comparative antimicrobial resistance and genomic diversity of Escherichia coli isolated from urinary tract infections in the community and in hospitals. J. Hosp. Infect. 41:273-279.[CrossRef][Medline]
  12. 7
  13. Ruiz, J., K. Simon, J. P. Horcajada, M. Velasco, M. Barranco, G. Roig, A. Moreno-Martinez, J. A. Martinez, T. Jimenez de Anta, J. Mensa, and J. Vila. 2002. Differences in virulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men. J. Clin. Microbiol. 40:4445-4449.[Abstract/Free Full Text]
  14. 8
  15. Thomson, R. B., Jr., and J. M. Miller. 2003. Specimen collection, transport, and processing: bacteriology, p. 286-330. In P. R. Murray, E. J. Baron, M. A. Pfaller, J. H. Jorgensen, and R. H. Yolken (ed.), Manual of clinical microbiology, 8th ed. ASM Press, Washington, D.C.
  16. 9
  17. Van Belkum, A., W. Goessens, C. van der Schee, N. Lemmens-den Toom, M. C. Vos, J. Cornelissen, E. Lugtenburg, S. de Marie, H. Verbrugh, B. Lowenberg, and H. Endtz. 2001. Rapid emergence of ciprofloxacin-resistant Enterobacteriaceae containing multiple gentamicin resistance-associated integrons in a Dutch hospital. Emerg. Infect. Dis. 7:862-871.[Medline]
S. J. Drews
T. Mazzulli
D. E. Low*

Toronto Medical Laboratories & Mount Sinai Hospital
Department of Microbiology
Room 1470, 600 University Avenue
Toronto, Ontario, Canada M5G 1X5

Phone: (416) 586-4435, Fax: (416) 586-8746, E-mail: dlow{at}mtsinai.on.ca


Journal of Clinical Microbiology, December 2005, p. 6221-6222, Vol. 43, No. 12
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.12.6221-6222.2005




This article has been cited by other articles:

  • Piatti, G., Mannini, A., Balistreri, M., Schito, A. M. (2008). Virulence Factors in Urinary Escherichia coli Strains: Phylogenetic Background and Quinolone and Fluoroquinolone Resistance. J. Clin. Microbiol. 46: 480-487 [Abstract] [Full Text]  

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