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Previous Article | Next Article 
J Bacteriol, April 1998, p. 1955-1958, Vol. 180, No. 7
0021-9193/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Frequency of Pilin Antigenic Variation in
Neisseria gonorrhoeae
Carla D.
Serkin and
H. Steven
Seifert*
Department of Microbiology-Immunology,
Northwestern University Medical School, Chicago, Illinois 60611
Received 22 September 1997/Accepted 26 January 1998
 |
ABSTRACT |
Variation of the pilus of Neisseria gonorrhoeae occurs
by the recombination of silent pilin DNA sequences into the pilin
expression locus. We have developed a quantitative, competitive reverse
transcription-PCR assay which measures the frequency of pilin antigenic
variation independently of changes in gonococcal colony morphology and
have determined this frequency within a gonococcal population. We have also studied the frequency of antigenic variation during growth and
have concluded that growth does not dramatically influence the
frequency of pilin antigenic variation, although a reproducible, twofold increase is observed upon the transition into late
log/stationary phase.
| |
TEXT |
The gram-negative diplococcus
Neisseria gonorrhoeae (the gonococcus) is the causative
agent of the sexually transmitted disease gonorrhea. Pili, filamentous
cell surface structures composed primarily of pilin monomers, mediate
the initial attachment of the gonococcus to host mucosal epithelial
cells (22) and are essential in the establishment of
infection, as nonpiliated gonococci fail to cause disease (9,
10).
Pilin is encoded by pilE, the pilin expression gene
(12). Gonococcal strain FA1090 contains one pilE
gene (21), and 19 silent pilin copies distributed among five
loci, with one silent copy associated with and located upstream of
pilE (21). Variation of the gonococcal pilus
results from the nonreciprocal transfer of partial pilin sequence
information from one silent pilin copy into pilE (5, 6,
17). The resultant, altered pilE gene sequence may
encode either an immunologically distinct pilin monomer which can be
assembled into functional pili (antigenic variation) or a pilin monomer
which is not produced or is inefficiently assembled, resulting in a
switch from a piliated (P+) to a nonpiliated
(P
) colony phenotype (colony morphology-based phase
variation) (1, 6, 23).
Since pilin antigenic variation and changes in gonococcal colony
morphology result from similar recombination-mediated processes, estimates of the frequency of antigenic variation have been based on
that of colony morphology-based phase variation (5, 23, 24,
27), which has been reported to be about 104 to
102 colony morphology variants per total CFUs (1,
16, 27). However, changes in gonococcal colony morphology can
also occur through processes distinct from those resulting in antigenic
variation, such as the deletion of pilE or phase variation
of PilC (7, 8, 16). Therefore, equating the frequency of
pilin antigenic variation to that of colony morphology-based phase
variation is not always appropriate. In order to quantitate
pilS to pilE recombination independently of
changes in colony morphology, we have combined a qualitative assay
which specifically detects pilS to pilE
recombination events (25), with a competitive reverse
transcription-PCR (RT-PCR) strategy. By using this assay, we have
determined the frequency of pilin antigenic variation during the growth
of a gonococcal population.
Development of a quantitative RT-PCR assay to measure the frequency
of pilin antigenic variation.
The quantitative RT-PCR assay
involves two PCRs which amplify pilE (Fig.
1A): a recombination-independent reaction
(primers PILRBS and CYS2R), which amplifies all pilE
template present (25), and a recombination-dependent
reaction (primers PILRBS and HV-1), which amplifies only those
pilE genes into which HV-1 amplifiable silent sequences have
recombined (11). To establish the assay, the frequency of
pilin recombination in the FA1090 variant 1-81-S2 wild type (WT)
(19), which does not initially contain HV-1 target sequences
in pilE (20), was determined. A constant volume
of total RNA isolated from a late-log-phase gonococcal population (target RNA) was mixed with a range of known concentrations of in
vitro-derived competitor RNA. The cloned competitor contains PILRBS
target sequences at the 5' end, an extra 100 bp of nonpilin DNA, and
both HV-1 and CYS2R target sequences at the 3' end, downstream of the
T7 polymerase promoter in pGEM-3 (pCDS2). This mixture of RNA was then
reverse transcribed, and the resulting cDNA was used as template for
both the recombination-independent and recombination-dependent PCRs,
which were performed in triplicate. By mixing target and competitor RNA
prior to the reverse transcription step, the competior template acted
as an internal control for the efficiencies of both the reverse
transcription reactions and PCRs (15). Target and competitor
PCR products were separated by gel electrophoresis (Fig. 1B), and the
amount of each product present was measured by densitometry. The
fluorescence intensities of the competitor products were then corrected
for size, allowing for a direct comparison between competitor and
target product molar amounts. The corrected competitor-to-target
product fluorescence ratio was plotted as a function of the relative
number of competitor RNA molecules present (Fig. 1C). The relative
number of competitor RNA molecules at which equal molar amounts of
target and competitor products are made reflects the concentration of
target pilE RNA template present in the original sample
(15). This calculation is independent of the level of
transcription of total mRNA in the gonococcal cultures, since the
amounts of both target RNAs are determined with regard to known
concentrations of competitor RNA. The total number of pilE
template molecules was calculated from the recombination-independent PCRs (primers PILRBS and CYS2R), while the number of pilE
template molecules containing sequences amplified by HV-1 (due to
recombination) was calculated from the recombination-dependent PCRs
(primers PILRBS and HV-1) (Fig. 1C). Once the amounts of total and HV-1 amplifiable pilE template present were calculated with
respect to the same competitor, they were used to determine the
proportion of pilE genes containing HV-1 amplifiable
sequences within the population. The frequency of HV-1 detection of
pilE in variant 1-81-S2 WT at late log phase was 1.99 × 102 HV-1 amplifiable pilE per total
pilE (HV-1 pilE/pilE). This is the first
quantitative measurement of the frequency of pilin antigenic variation
within a gonococcal population and independent of colony morphology-based phase variation.
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FIG. 1.
Quantitation of pilin recombination in variant 1-81-S2
WT at late log phase using competitive RT-PCR. (A) Cartoon of PCR assay
detecting pilS-to-pilE recombination. The major
conserved regions of pilE and pilS are
represented by the shaded boxes, and variable sequences are represented
by either white or speckled boxes. S/C represents the conserved, 3'
Sma/Cla repeat. The transcription start site of pilE is
indicated by +1. PILRBS targets the ribosomal binding site of the
expression locus and is pilE specific (26). CYS2R
targets the conserved cys2 region of all pilin copies
(25), while HV-1 targets the HV sequences of
pilS1 copy 4 and pilS6 copy 1 (19,
20). Recombination-independent primers PILRBS and CYS2R amplify
all pilE templates present, generating a 516-bp product
(thick line). Recombination-dependent primers PILRBS and HV-1 yield a
460-bp product only if HV-1 target sequences have recombined into
pilE (thin line). (B) Representative agarose gels of the
recombination-independent and -dependent PCR products. The products of
one recombination-independent PCR and one recombination-dependent PCR
are shown. In both gels, the top band is the competitor PCR product,
and the bottom band is the target PCR product. (C) Graphs of the PCR
data. The x axis shows the relative number of competitor RNA
molecules added for each cDNA reaction, as determined by
spectrophotometry at an optical density of 260 nm. The y
axis shows the corrected competitor-to-target product fluorescence
ratio. A line of least-squares fit (dashed) with 95% confidence level
(dotted lines) is shown. The amount of competitor RNA present when
equal molar amounts of competitor and target products are made (solid
vertical and horizontal lines, respectively) equals the amount of
target template present in the original reaction. Total pilE
is calculated from the recombination-independent reactions, and HV-1
ampifiable pilE is calculated from the
recombination-dependent reactions.
|
|
Contribution of HV-1 amplifiable silent copies to the frequency of
antigenic variation.
The HV regions of pilS1 copy 4 and
pilS6 copy 1 in FA1090 contain identical sequences that are
specifically targeted by HV-1 (20). However, the HV regions
of other silent copies contain sequences similar to HV-1 and therefore
may have also been amplified during the recombination-dependent
reaction. In order to determine the contribution of the HV-1-specific
silent copies to the calculated frequency, recombination-dependent PCR
products from the late log phase of preinduced 1-81-S2 recA6
and of 1-81-S2 recA6 induced at time zero
(t0) (see below) were cloned and sequenced. None of the 54 clones sequenced contained the original pilS2 copy
1 sequence in the HV region, confirming that the assay detected the
transfer of silent-copy HV sequences into pilE (Table
1). Fifty percent of pilE PCR
products contained HV-1 target-specific pilS1 copy 4 or
pilS6 copy 1 sequences in the HV region. The other clones
sequenced contained HV sequences from a subset of other silent pilin
copies (20), each of which contained two to five mismatches
to the HV-1 primer. Therefore, although this RT-PCR assay does not
detect recombination solely from pilS1 copy 4 or pilS6 copy 1 into pilE, it accurately and
reproducibly quantitates the recombination frequency of HV-1
amplifiable silent pilin sequences into pilE.
Effect of growth on the frequency of gonococcal pilin antigenic
variation.
Since this competitive RT-PCR assay provides a
reproducible measurement of the frequency of pilin antigenic variation
within a gonococcal population, we used it to study the effect of
growth. We used two FA1090 variants which do not initially
contain HV-1 amplifiable sequences in pilE; 1-81-S2 WT
(19) and 1-81-S2 recA6 (11). Variant
1-81-S2 recA6 contains the recA6 allele, in which lac regulatory sequences control the transcription of
recA. In the absence of
isopropyl-
-D-thiogalactopyranoside (IPTG), transcription of recA is undetectable, and recA6 variants are
deficient in recombination. However, in the presence of IPTG,
recA is transcribed, and recombination-mediated processes,
such as pilin antigenic variation, can occur (18). The use
of variant 1-81-S2 recA6 ensured that the initial
pilE sequences within the gonococcal population did not
contain HV-1 target sequences. Moreover, in the absence of IPTG,
recombination-dependent product from the PCR with primers PILRBS and
HV-1 was not detected at any point during growth (data not shown).
The frequency of pilin antigenic variation was determined for mid-log,
late log, and late log/stationary phases of growth of these two FA1090
variants. Following the induction of recA with IPTG at
t0, there was a considerable increase in the
frequency by which HV-1 sequences recombined into pilE over
time in 1-81-S2 recA6 (Fig.
2). A 3.8-fold increase, from 4.97 × 104 to 1.87 × 103 HV-1
pilE/pilE, was observed between mid- and late log phases, followed by a 2-fold increase, from 1.87 × 103 to
3.86 × 103 HV-1 pilE/pilE, between late
log and late log/stationary phases. Rates of variation, which reflect
the number of antigenic variants per generation, were calculated during
exponential growth of the gonococcal population and were 2.76 × 104 variants per generation (var/gen) from
t0 to mid-log, 4.90 × 104
var/gen from mid-log to late log, and 3.36 × 104
var/gen from t0 to late log. The increase in the
frequency over time suggested that the number of gonococci within the
population containing recombinant, HV-1 amplifiable pilE
accumulated from the time recombination could occur with the induction
of recA through to late log/stationary phase of growth.
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FIG. 2.
Average frequency of pilin antigenic variation with
respect to growth phase. The frequency of antigenic variation is
expressed as HV-1 pilE/pilE for mid-log, late log, and late
log/stationary phases of 1-81-S2 recA6 induced at
t0, preinduced 1-81-S2 recA6 and
1-81-S2 WT. Six to 15 individual sets of PCRs were performed for each
time point, and the standard errors of the means are shown by the error
bars. The asterisk indicates a significant difference relative to the
value at late log phase by the Student t test with
P < 0.05.
|
|
In order to determine whether the level of HV-1 amplifiable
pilE in variant 1-81-S2 recA6 reaches an
equilibrium within a population undergoing continual pilin
recombination, this variant was preinduced with IPTG prior to the
growth curve assayed. The frequency of pilin recombination in variant
1-81-S2 recA6 preinduced with IPTG remained relatively
constant throughout early growth and with repeats of growth, with
4.48 × 103 HV-1 pilE/pilE at mid-log and
3.97 × 103 HV-1 pilE/pilE at late log.
There was a twofold increase in this frequency upon late log/stationary
phase relative to late log from 3.97 × 103 to
8.05 × 103 HV-1 pilE/pilE (Fig. 2). The
consistency in the frequency over time suggested the presence of an
equilibrium subpopulation of HV-1 amplifiable
pilE-expressing gonococci within the population which was
not drastically influenced by growth.
With variant 1-81-S2 WT, the frequency of pilin antigenic variation
also remained relatively constant throughout the exponential phase of
growth, with 2.59 × 102 HV-1 pilE/pilE
at mid-log and 3.35 × 102 HV-1 pilE/pilE
at late log (Fig. 2). The rate of variation over this period of growth
was 7.92 × 103 var/gen. Overall, the frequency by
which HV-1 target sequences recombined into pilE was
approximately 10-fold higher in the 1-81-S2 WT variant than in the
1-81-S2 recA6 variant, presumably due to the lower levels of
recA mRNA present in fully induced recA6 variants compared to those in the WT counterparts (18). The frequency of pilin antigenic variation in the WT variant was consistent both
throughout early growth and throughout repeated growth curves assayed.
This further suggested the presence of an equilibrium subpopulation of
variant gonococci within the population which was not affected by
growth. In contrast, there was a significant twofold increase in the
frequency of pilin recombination upon late log/stationary phase
relative to late log from 3.35 × 102 to 5.92 × 102 HV-1 pilE/pilE. This suggested that
some event during the transition into the late log/stationary phase of
growth may have influenced pilin recombination. Stationary-phase
effects have been reported in N. gonorrhoeae, such as an
enhancement in gonococcal autolysis (2, 3, 13). This
increased autolysis, coupled with the natural transformation competence
of gonococci, has previously been proposed to affect pilin sequence
changes (4, 14). It is possible that an increase in
autolysis and the subsequent uptake of released DNA by intact, unlysed
gonococci may account for the increase in the frequency of pilin
antigenic variation observed upon late log/stationary phase.
Conclusions.
This quantitative RT-PCR assay measures pilin
antigenic variation independently of changes in gonococcal colony
morphology, thus taking into account the fact that pilin antigenic and
colony morphology-based phase variation are separable events.
Furthermore, this assay can be used to quantitate and to compare the
frequency of gonococcal pilin antigenic variation between different
variants, growth conditions, or mutants and is adaptable for the
detection and quantitation of recombination from other silent pilin
copies into pilE. Using this quantitative assay to examine
pilin antigenic variation frequencies during growth, we can conclude
that growth does not dramatically affect the frequency of pilin
antigenic variation in a gonococcal population but that a reproducible, twofold increase in the frequency does occur upon transition into the
late log/stationary phase of growth.
| |
ACKNOWLEDGMENTS |
This work was supported by grant RO1AI33493 from the National
Institutes of Health.
We thank Joe Dillard, Becky Howell-Adams, Cindy Long, and Ian Mehr for
critical reading of this manuscript.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Microbiology-Immunology, Northwestern University Medical School, 303 East Chicago Ave., Chicago, IL, 60611. Phone: (312) 503-9788. Fax:
(312) 503-1339. E-mail: h-seifert{at}nwu.edu.
| |
REFERENCES |
| 1.
|
Bergström, S.,
K. Robbins,
J. M. Koomey, and J. Swanson.
1986.
Piliation control mechanisms in Neisseria gonorrhoeae.
Proc. Natl. Acad. Sci. USA
83:3890-3894[Abstract/Free Full Text].
|
| 2.
|
Dillard, J. P., and H. S. Seifert.
1997.
A peptidoglycan hydrolase similar to bacteriophage endolysins acts as an autolysin in Neisseria gonorrhoeae.
Mol. Microbiol.
25:893-902[Medline].
|
| 3.
|
Elmros, T.,
L. G. Burman, and G. D. Bloom.
1976.
Autolysis of Neisseria gonorrhoeae.
J. Bacteriol.
126:969-976[Abstract/Free Full Text].
|
| 4.
|
Gibbs, C. P.,
B. Reimann,
E. Schultz,
A. Kaufmann,
R. Haas, and T. F. Meyer.
1989.
Reassortment of pilin genes in Neisseria gonorrhoeae occurs by two distinct mechanisms.
Nature
338:651-652[Medline].
|
| 5.
|
Haas, R., and T. F. Meyer.
1986.
The repertoire of silent pilus genes in Neisseria gonorrhoeae: evidence for gene conversion.
Cell
44:107-115[Medline].
|
| 6.
|
Hagblom, P.,
E. Segal,
E. Billyard, and M. So.
1985.
Intragenic recombination leads to pilus antigenic variation in Neisseria gonorrhoeae.
Nature
315:156-158[Medline].
|
| 7.
|
Jonsson, A.,
D. Ilver,
P. Falk,
J. Pepose, and S. Normark.
1994.
Sequence changes in the pilus subunit lead to tropism variation of Neisseria gonorrhoeae to human tissue.
Mol. Microbiol.
13:403-416[Medline].
|
| 8.
|
Jonsson, A.,
J. Pfeifer, and S. Normark.
1992.
Neisseria gonorrhoeae PilC expression provides a selective mechanism for structural diversity of pili.
Proc. Natl. Acad. Sci. USA
89:3204-3208[Abstract/Free Full Text].
|
| 9.
|
Kellogg, D. S., Jr.,
I. R. Cohen,
L. C. Norins,
A. L. Schroeter, and G. Reising.
1968.
Neisseria gonorrhoeae. II. Colonial variation and pathogenicity during 35 months in vitro.
J. Bacteriol.
96:596-605[Abstract/Free Full Text].
|
| 10.
|
Kellogg, D. S., Jr.,
W. L. Peacock, Jr.,
W. E. Deacon,
L. Brown, and C. I. Pirkle.
1963.
Neisseria gonorrhoeae. I. Virulence genetically linked to clonal variation.
J. Bacteriol.
85:1274-1279[Abstract/Free Full Text].
|
| 11.
|
Mehr, I. J., and H. S. Seifert.
1997.
Random shuttle mutagenesis: gonococcal mutants deficient in pilin antigenic variation.
Mol. Microbiol.
23:1121-1131[Medline].
|
| 12.
|
Meyer, T. F.
1982.
Pilus expression in Neisseria gonorrhoeae involves chromosomal rearrangement.
Cell
30:45-52[Medline].
|
| 13.
|
Morse, S. A., and L. Bartenstein.
1974.
Factors affecting autolysis of Neisseria gonorrhoeae.
Proc. Soc. Exp. Biol. Med.
145:1418-1421[Medline].
|
| 14.
|
Norlander, L.,
J. Davies,
A. Norqvist, and S. Normark.
1979.
Genetic basis for colonial variation in Neisseria gonorrhoeae.
J. Bacteriol.
138:762-769[Abstract/Free Full Text].
|
| 15.
|
Piatak, M. J.,
K. Luk,
B. Williams, and J. D. Lifson.
1993.
Quantitative competitive polymerase chain reaction for accurate quantitation of HIV DNA and RNA species.
BioTechniques
14:70-80.
[Medline] |
| 16.
|
Segal, E.,
E. Billyard,
M. So,
S. Storzbach, and T. F. Meyer.
1985.
Role of chromosomal rearrangement in N. gonorrhoeae pilus phase variation.
Cell
40:293-300[Medline].
|
| 17.
|
Segal, E.,
P. Hagblom,
H. S. Seifert, and M. So.
1986.
Antigenic variation of gonococcal pilus involves assembly of separated silent gene segments.
Proc. Natl. Acad. Sci. USA
83:2177-2181[Abstract/Free Full Text].
|
| 18.
|
Seifert, H. S.
1997.
Insertionally inactivated and inducible recA alleles for use in Neisseria.
Gene
199:215-220.
|
| 19.
|
Seifert, H. S.,
C. J. Wright,
A. E. Jerse,
M. S. Cohen, and J. G. Cannon.
1994.
Multiple gonococcal pilin antigenic variants are produced during experimental human infections.
J. Clin. Invest.
93:2744-2749.
|
| 20.
| Snodgrass, T. L., and J. G. Cannon. 1997. Personal communication.
|
| 21.
|
Snodgrass, T. L.,
J. A. F. Dempsey, and J. G. Cannon.
1994.
The repertoire of silent pilin gene copies and their chromosomal location is similar but not identical in gonococcal strains FA1090 and MS11, p. 113-115.
Neisseria 94 Proceedings from the Ninth International Pathogenic Neisseria Conference
.
|
| 22.
|
Swanson, J.
1973.
Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells.
J. Exp. Med.
137:571-589[Abstract].
|
| 23.
|
Swanson, J.,
S. Bergström,
K. Robbins,
O. Barrera,
D. Corwin, and J. M. Koomey.
1986.
Gene conversion involving the pilin structural gene correlates with pilus+ pilus changes in Neisseria gonorrhoeae.
Cell
47:267-276[Medline].
|
| 24.
|
Swanson, J.,
S. Morrison,
O. Barrera, and S. Hill.
1990.
Piliation changes in transformation-defective gonococci.
J. Exp. Med.
171:2131-2139[Abstract/Free Full Text].
|
| 25.
|
Wainwright, L. A.,
K. H. Pritchard, and H. S. Seifert.
1994.
A conserved DNA sequence is required for efficient gonococcal pilin antigenic variation.
Mol. Microbiol.
13:75-87[Medline].
|
| 26.
|
Wright, C. J.,
A. E. Jerse,
M. S. Cohen,
J. G. Cannon, and H. S. Seifert.
1994.
Nonrepresentative PCR amplifications of variable gene sequences in clinical specimens containing dilute, complex mixtures of microorganisms.
J. Clin. Microbiol.
32:464-468[Abstract/Free Full Text].
|
| 27.
|
Zhang, Q. Y.,
D. DeRyckere,
P. Lauer, and J. M. Koomey.
1992.
Gene conversion in Neisseria gonorrhoeae: evidence for its role in pilus antigenic variation.
Proc. Natl. Acad. Sci. USA
89:5366-5370[Abstract/Free Full Text].
|
J Bacteriol, April 1998, p. 1955-1958, Vol. 180, No. 7
0021-9193/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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