Previous Article | Next Article 
Journal of Clinical Microbiology, February 2000, p. 941-942, Vol. 38, No. 2
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
LETTERS TO THE EDITOR
Molecular Basis for Distinction of the ET-15 Clone within
the ET-37 Complex of Neisseria meningitidis
 |
LETTER |
The species Neisseria meningitidis comprises a large
variety of genetically different clones, which are defined either by multilocus enzyme electrophoresis (MLEE) (2) or by
multilocus sequence typing (MLST) (5) of housekeeping genes.
One cluster of related clones causing predominantly epidemic serogroup
C disease, i.e., the electrophoretic type 37 (ET-37) complex, has been
defined by MLEE. A particular clone of the ET-37 complex, ET-15, arose several years ago in Canada (1, 6) and has spread worldwide since then (4). ET-15 meningococci tend to be more virulent than other members of the ET-37 complex, and attack and fatality rates,
as well as the proportion of sequelae, have been reported to exceed the
rates observed for other members of the ET-37 complex (3, 4,
6). Therefore, attempts to distinguish ET-15 from other clones of
the ET-37 complex have been made to guide public health actions
undertaken in case of outbreaks of ET-15 disease. Until now, ET-15
meningococi could be solely identified by MLEE, because this new clone
differed by a rarely occurring FumC allele (FumC2) from most other
ET-37 complex strains, which express a FumC1 allele (1).
However, the use of MLEE is restricted to a few specialized
laboratories worldwide. Pulsed-field gel electrophoresis (PFGE) using
the enzyme SpeI revealed restriction patterns which are
specific to ET-15 (J. Jelfs, R. Munro, F. Ashton, N. Rawlinson, and D. A. Caugant, Abstr. 11th Int. pathog. Neisseria Conf., p. 5, 1998), but
PFGE is far too time-consuming to be a viable alternative to MLEE.
Sequencing of the fumC gene has been added to the original MLST scheme for meningococci in order to distinguish ET-15, but no
sequence information specific to ET-15 meningococci was found in the
part of the gene sequenced by MLST (fumC gene position 776 to 1,230) (http://mlst.zoo.ox.ac.uk/). We therefore compared the
sequences upstream of position 776 of the fumC gene of ET-15 meningococci with those of other members of the ET-37 complex. For this
purpose, the fumC gene was amplified using the primers fumC-A1 and fumC-A2 (1). The PCR
product was sequenced using the primer fumC-P3
(5'-CGTAAAAGCCCTGCGCGAC-3'). At position 640 we observed a
point mutation in the fumC gene of ET-15 meningococci, which
showed an A instead of a G in other ET-37 complex
strains. This nonsynonymous change
results in the expression of a basic lysine instead of an acidic glutamate (Fig. 1). We suggest that this
mutation is responsible for the different MLEE migration pattern of the
ET-15 FumC. The point mutation was consistantly found in 13 ET-15
strains from various geographical origins, but not in seven ET-37
complex strains other than ET-15 (Table 1). Thus, the point mutation at
posiiton 640 of the fumC gene is a clone-specific
characteristic which permits the distintion of ET-15 from other ET-37
complex strains. We therefore suggest that sequencing of the
fumC gene should include position 640 in order to identify
this especially virulent variant.
| |
REFERENCES |
| 1.
|
Ashton, F. E.,
J. A. Ryan,
A. Borczyk,
D. A. Caugant,
L. Mancino, and D. Huang.
1991.
Emergence of a virulent clone of Neisseria meningitidis serotype 2a that is associated with meningococcal gorup C disease in Canada.
J. Clin. Microbiol.
29:2489-2493[Abstract/Free Full Text].
|
| 2.
|
Caugant, D. A.,
K. Bovre,
P. Gaustad,
K. Bryn,
E. Holten,
E. A. Hoiby, and L. O. Froholm.
1986.
Multilocus genotypes determined by enzyme electrophoresis of Neisseria meningitidis isolated from patients with systemic disease and from healthy carriers.
J. Gen. Microbiol.
132:641-652[Abstract/Free Full Text].
|
| 3.
|
Erickson, L., and P. De Wals.
1998.
Complications and sequelae of meningococcal disease in Quebec, Canada, 1990-1994.
Clin. Infect. Dis.
26:1159-1164[Medline].
|
| 4.
|
Krizova, P., and M. Musilek.
1995.
Changing epidemiology of meningococcal invasive disease in the Czech republic cause by new clone Neisseria meningitidis C:2a: P1.2(P1.5), ET-15/37.
Cent. Eur. J. Public Health
3:189-194[Medline].
|
| 5.
|
Maiden, M. C.,
J. A. Bygraves,
E. Feil,
G. Morelli,
J. E. Russell,
R. Urwin,
Q. Zhang,
J. Zhou,
K. Zurth,
D. A. Caugant,
I. M. Feavers,
M. Achtman, and B. G. Spratt.
1998.
Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms.
Proc. Natl. Acad. Sci. USA
95:3140-3145[Abstract/Free Full Text].
|
| 6.
|
Whalen, C. M.,
J. C. Hockin,
A. Ryan, and F. Ashton.
1995.
The changing epidemiology of invasive meningococcal disease in Canada, 1985 through 1992. Emergence of a virulent clone of Neisseria meningitidis.
JAMA
273:390-394[Abstract/Free Full Text].
|
| | | | |
Ulrich Vogel
Heike Claus
Matthias Frosch
Institut für Hygiene und Mikrobiologie
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg, Germany
*Phone: 49(931)201
3902
Fax: 49(932)201 3445
E-mail: uvogel{at}hygiene.uni-wuerzburg.de
|
| | | | |
Dominique A. Caugant
WHO Collaborating Centre for Reference
and Research
on Meningococci
National Institute of Health
Oslo, Norway
|
Journal of Clinical Microbiology, February 2000, p. 941-942, Vol. 38, No. 2
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Beddek, A. J., Li, M.-S., Kroll, J. S., Jordan, T. W., Martin, D. R.
(2009). Evidence for Capsule Switching between Carried and Disease-Causing Neisseria meningitidis Strains. Infect. Immun.
77: 2989-2994
[Abstract]
[Full Text]
-
Schmink, S., Watson, J. T., Coulson, G. B., Jones, R. C., Diaz, P. S., Mayer, L. W., Wilkins, P. P., Messonnier, N., Gerber, S. I., Fischer, M.
(2007). Molecular Epidemiology of Neisseria meningitidis Isolates from an Outbreak of Meningococcal Disease among Men Who Have Sex with Men, Chicago, Illinois, 2003. J. Clin. Microbiol.
45: 3768-3770
[Abstract]
[Full Text]
-
Cameron, M. L., Tsang, R. S. W.
(2007). Analysis of Phenotypic Variants of the Serogroup C ET-15 Clone of Neisseria meningitidis by Pulsed-Field Gel Electrophoresis. J. Clin. Microbiol.
45: 2351-2352
[Full Text]
-
Elias, J., Vogel, U.
(2007). IS1301 Fingerprint Analysis of Neisseria meningitidis Strains Belonging to the ET-15 Clone. J. Clin. Microbiol.
45: 159-167
[Abstract]
[Full Text]
-
Birtles, A., Hardy, K., Gray, S. J., Handford, S., Kaczmarski, E. B., Edwards-Jones, V., Fox, A. J.
(2005). Multilocus Sequence Typing of Neisseria meningitidis Directly from Clinical Samples and Application of the Method to the Investigation of Meningococcal Disease Case Clusters. J. Clin. Microbiol.
43: 6007-6014
[Abstract]
[Full Text]
-
Yazdankhah, S. P., Kriz, P., Tzanakaki, G., Kremastinou, J., Kalmusova, J., Musilek, M., Alvestad, T., Jolley, K. A., Wilson, D. J., McCarthy, N. D., Caugant, D. A., Maiden, M. C. J.
(2004). Distribution of Serogroups and Genotypes among Disease-Associated and Carried Isolates of Neisseria meningitidis from the Czech Republic, Greece, and Norway. J. Clin. Microbiol.
42: 5146-5153
[Abstract]
[Full Text]
-
Law, D. K. S., Henderson, A. M., Tsang, R. S. W.
(2004). DNA Sequence Analysis of the PorB Protein of Nonserotypeable Serogroup C ET-15 Meningococci Suggests a Potential Mutational Hot Spot on Their Serotype Antigens. J. Clin. Microbiol.
42: 2718-2723
[Abstract]
[Full Text]
-
Tsang, R. S. W., Tsai, C. M., Zhu, P., Ringuette, L., Lorange, M., Law, D. K. S.
(2004). Phenotypic and Genetic Characterization of a Unique Variant of Serogroup C ET-15 Meningococci (with the Antigenic Formula C:2a:P1.7,1) Causing Invasive Meningococcal Disease in Quebec, Canada. J. Clin. Microbiol.
42: 1460-1465
[Abstract]
[Full Text]
-
Tsang, R. S.W., Kiefer, L., Law, D. K. S., Stoltz, J., Shahin, R., Brown, S., Jamieson, F.
(2003). Outbreak of Serogroup C Meningococcal Disease Caused by a Variant of Neisseria meningitidis Serotype 2a ET-15 in a Community of Men Who Have Sex with Men. J. Clin. Microbiol.
41: 4411-4414
[Abstract]
[Full Text]
-
BALMER, P., BORROW, R., MILLER, E.
(2002). Impact of meningococcal C conjugate vaccine in the UK. J Med Microbiol
51: 717-722
[Abstract]
[Full Text]
-
Clarke, S C, Reid, J, Thom, L, Denham, B C, Edwards, G F S
(2002). Laboratory confirmation of meningococcal disease in Scotland, 1993-9. J. Clin. Pathol.
55: 32-36
[Abstract]
[Full Text]
-
Clarke, S. C., Diggle, M. A., Edwards, G. F. S.
(2001). Semiautomation of Multilocus Sequence Typing for the Characterization of Clinical Isolates of Neisseria meningitidis. J. Clin. Microbiol.
39: 3066-3071
[Abstract]
[Full Text]
-
Tzanakaki, G., Urwin, R., Musilek, M., Kriz, P., Kremastinou, J., Pangalis, A., Blackwell, C. C., Maiden, M. C. J.
(2001). Phenotypic and Genotypic Approaches to Characterization of Isolates of Neisseria meningitidis from Patients and Their Close Family Contacts. J. Clin. Microbiol.
39: 1235-1240
[Abstract]
[Full Text]
