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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
Virulence Factors in Escherichia coli

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.

REFERENCES
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 - 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]
3 - 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]
4 - 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.
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.[CrossRef][Medline]
6 - 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]
7 - 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]
8 - 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]
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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
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Authors' Reply

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).

REFERENCES
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 - 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]
3 - 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.
4 - 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.
5 - 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.
6 - 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]
7 - 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]
8 - 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.
9 - 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]
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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
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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
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