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Infection and Immunity, September 1999, p. 4557-4562, Vol. 67, No. 9
Department of Safety Research on Biologics,
Received 15 March 1999/Returned for modification 27 April
1999/Accepted 23 June 1999
A Mycoplasma pneumoniae cytadhesin P1 gene with novel
nucleotide sequence variation has been identified. Four clinical
strains of M. pneumoniae were found to carry this type of
P1 gene. This new P1 gene is similar to the known group II P1 genes but
possesses novel sequence variation of approximately 300 bp in the
RepMP2/3 region. The position of the new variable region is distant
from the previously reported variable regions known to differ between group I and II P1 genes. Two sequences closely homologous to this new
variable region were found within the repetitive sequences outside the
P1 gene of the M. pneumoniae M129 genome. This suggests that the new P1 gene was generated by DNA recombination between repetitive sequences and the P1 gene locus. The finding of this new
type of P1 gene supports the hypothesis that the repetitive sequences
of the M. pneumoniae genome serve as a
reservoir to generate antigenic variation of the cytadhesin P1 gene.
Mycoplasma pneumoniae is
a causative agent of tracheobronchitis and primary atypical pneumonia
in humans. Adherence to host respiratory epithelium (cytadherence) is a
crucial step in M. pneumoniae infection and successful
colonization (10, 23). Cytadherence is mediated by the
specialized attachment organelle, a tip-like structure found in
M. pneumoniae cells. A number of different mycoplasmal
proteins take part in the formation of the attachment organelle and the
cytadherence process (17, 18). A 170-kDa protein, P1, is
densely clustered at the attachment organelle (6, 9) and is
a major adhesion protein that directly binds to the receptor molecule
of the host cells (23). A mutant strain of M. pneumoniae that lacks P1 protein fails to attach to host cells and
is avirulent (1, 20). It has been reported that specific
anti-P1 monoclonal antibodies can block cytadherence (15,
19). Through use of these monoclonal antibodies, the cytadherence-mediating domains of P1 protein have also been identified (5, 7). The P1 protein is a major M. pneumoniae
immunogen and induces a strong immunological response in pneumonia
patients (11, 21). However, only a small fraction of all of
the anti-P1 antibodies present in patients' sera can mediate
cytadherence-inhibiting activity. This is because the
cytadherence-mediating domains of the P1 protein are different from the
immunodominant epitopes which trigger humoral responses
(14, 16, 23).
The gene encoding the P1 protein forms an operon together with two open
reading frames, ORF4 and ORF6 (13). It is known that only
one copy of functional full-length P1 gene is to be found in the
M. pneumoniae genome, although two-thirds of the P1 gene
sequence exist as multiple copies (27, 34). Two repetitive regions exist in the P1 gene. One region is designated RepMP4 and
is located at the 5' end of the coding region, whereas the other,
designated RepMP2/3, is located at the 3' end (25).
According to complete genome sequencing data for strain M129 of
M. pneumoniae (8), a total of 8 copies, including
the copies contained in the P1 gene, of the RepMP4 sequence and 10 copies of the RepMP2/3 sequence are dispersed throughout the
genome. These RepMP sequences are closely related but not identical to
one another, so it is conceivable that recombination between
the P1 gene and RepMP sequences could generate a large sequence
diversity of P1 genetic and antigenic variants. Herein may reside one
of the mechanisms that enables M. pneumoniae to escape from
host immune responses. Consistent with this hypothesis, sequence
polymorphism was observed within P1 genes of clinical isolates of
M. pneumoniae (4), and two types of P1 gene
sequences have been reported (group I and group II) (28).
However, analyses of P1 genes from a number of clinical isolates
of M. pneumoniae by Southern blotting (4, 29,
30), DNA fingerprinting (33), and restriction
fragment length polymorphism (RFLP) (26) techniques revealed
only two types of P1 genes. Since there are only two types of P1 genes,
the function of the RepMP sequence for generating P1 gene
diversity is still obscure. Therefore, to clarify the role of the
RepMP sequences, it is essential to find new types of P1 gene
sequences and to analyze the mechanisms that generate P1 gene diversity.
In this study, we determined the precise RFLP patterns of P1 gene
sequences from clinical isolates of M. pneumoniae and found certain strains which possess a new type of P1 gene
sequence. The origin of this sequence variation is discussed below.
M. pneumoniae strains and culture.
Two hundred
eighteen clinical strains of M. pneumoniae were isolated
from pneumonia patients in Japan during the period of 1979 to 1998. Of
these clinical strains, 1 was isolated in Nagasaki Prefecture, 11 were
isolated in Hokkaido Prefecture, and the others were collected in
Kanagawa Prefecture. M. pneumoniae strains were cultured in
PPLO medium (2.1% PPLO broth [Difco Laboratories, Detroit, Mich.],
0.25% glucose, 0.002% phenol red, 10% horse serum [Gibco BRL,
Rockville, Md.], 200 units of penicillin G per ml) at 37°C. The
strains were also cloned on PPLO agar plates (PPLO medium, 1.2% agar)
to prevent mixed cultures before experiments were performed.
Isolation of genomic DNA from M. pneumoniae
cells.
Genomic DNAs from M. pneumoniae strains were
isolated as follows: M. pneumoniae cells were collected from
1 ml of culture medium by centrifugation. The pellets were suspended in
0.5 ml of lysis buffer (150 mM NaCl, 20 mM sodium citrate, 10 mM
Tris-HCl [pH 7.5], 1 mM EDTA, 1 mg of proteinase K per ml, 20 µg of
RNase A per ml, 1% sodium dodecyl sulfate) and incubated at 55°C for 30 min. Lysates were kept at 37°C overnight and then treated twice with 0.5 ml of phenol-chloroform. Genomic DNAs were
precipitated with 1 ml of isopropanol and then washed with 70% ethanol
and dried.
PCR-RFLP analysis of M. pneumoniae strains.
The
PCR-RFLP typing method was based on a previous report (26).
PCR primers ADH1 (CTGCCTTGTCCAAGTCCACT) and ADH2
(AACCTTGTCGGGAAGAGCTG) were used to amplify P1 gene DNA
containing RepMP4 sequences. Primers ADH3 (CGAGTTTGCTGCTAACGAGT)
and ADH4 (CTTGACTGATACCTGTGCGG) were used to amplify
the RepMP2/3 region (see Fig. 1A). Amplified DNA fragments were
digested with the HaeIII restriction enzyme and analyzed by
2% agarose gel electrophoresis.
DNA sequencing analysis.
The RepMP2/3 region of the M. pneumoniae 309 P1 gene was amplified by PCR with oligonucleotide
primers ADH3-EC (AAGGAATTCGAGTTTGCTGCTAACGAGT) and ADH4-PS (GTTCTGCAGCTTGACTGATACCTGTGCGG).
ADH3-EC and ADH4-PS are ADH 3 and ADH4 primers with a restriction
enzyme site (EcoRI or PstI) (underlined) at the
5' end. The RepMP2/3-5 region of strain 309 was cloned by PCR with the
oligonucleotide primers 5F
(TAAGAATTCCAATAACACCTTTAAAG) and 5R
(AGCTGCAGTTAGCAACGCTGCAAAGGCG). The RepMP2/3-6
region of strain 309 was also cloned by PCR with, primers 6F
(AAGGAATTCTGACCCTAGTGTGGCGAAAA) and 6R
(TTCCTGCAGGGAGAGATCCACGCCAGATT). These primers
also contain either an EcoRI or a PstI
restriction site (underlined). Amplified fragments were digested with
EcoRI and PstI and ligated into the
EcoRI and PstI sites of the Bluescript II SK+
plasmid (Stratagene, La Jolla, Calif.). Sequencing of cloned PCR
fragments was performed by a primer walking strategy with the BigDye terminator cycle sequencing kit and the DNA sequencer ABI
PRISM 310 (Perkin-Elmer Applied Biosystems, Foster City, Calif.).
Nucleotide sequence accession number.
The nucleotide
sequence data reported in this paper will appear in the
DDBJ/EMBL/GenBank nucleotide sequence databases under accession no.
AB024618.
Identification of new variable sequences in functional P1 genes
from clinical strains of M. pneumoniae.
To seek new
nucleotide sequences in the functional P1 gene, we analyzed 218 clinical strains of M. pneumoniae by a PCR-RFLP typing
method (26). In this approach, oligonucleotide PCR primers ADH1, ADH2, ADH3, and ADH4, which are derived from single-copy regions
flanking the RepMP regions of the P1 gene (Fig.
1A), were employed. This means that only
functional P1 gene sequences were able to be amplified. These amplified
P1 gene fragments were then typed with the restriction enzyme
HaeIII to generate characteristic RFLP patterns.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Identification of a New Variable Sequence in the P1 Cytadhesin
Gene of Mycoplasma pneumoniae: Evidence for the Generation
of Antigenic Variation by DNA Recombination between Repetitive
Sequences
![]()
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
![]()
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
![]()
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
![]()
RESULTS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

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FIG. 1.
(A) Schematic diagram of the group II P1 gene. The
regions of two repetitive sequence groups (RepMP4 and RepMP2/3) are
indicated. Arrows indicate the binding sites of the PCR primers
employed for RFLP analysis. The inside region between the ADH3 and ADH4
primer sites is shown magnified below, and the positions of
HaeIII restriction sites (H) are indicated. Two
HaeIII sites which were missing in the M. pneumoniae 309 P1 gene are marked with asterisks. The solid bar
indicates the region of variable sequence found in the M. pneumoniae 309 P1 gene (see Fig. 2 and text). The open bar
indicates the variable region between the group I and group II P1
genes. (B) PCR-RFLP analysis of M. pneumoniae P1 genes. P1
gene DNA fragments amplified by PCR were digested with the
HaeIII restriction enzyme and analyzed by 2% agarose gel
electrophoresis. PCR primers used for the analysis are shown at the
top. Lanes: M, DNA size marker (
X174 HincII digest); 1 and 3, M. pneumoniae FH; 2 and 4, M. pneumoniae
309. The difference in the RFLP pattern of M. pneumoniae 309 is indicated by an arrow.
DNA sequence analysis of the RepMP2/3 region of the functional P1
gene from M. pneumoniae 309.
The nucleotide sequence
of the RepMP2/3 region from the M. pneumoniae 309 P1 gene
was then analyzed. The gene was cloned by PCR and ligated into the
Bluescript II SK+ plasmid. To avoid the confounding factor of mutations
generated in the course of the PCRs, three independent plasmid clones
were sequenced. Their sequences were compared to P1 gene sequences
previously reported for the group I strain M129 (13) and for
the group II strain TW7-5 (28) of M. pneumoniae.
Although we used M. pneumoniae FH in the PCR-RFLP analysis
as a representative group II strain, we utilized the P1 gene sequence
of strain TW7-5 here for comparison. This is because the complete
nucleotide sequence of the M. pneumoniae FH P1 gene has not
been reported. However, the theoretical RFLP patterns of the M. pneumoniae TW7-5 P1 gene indicate that the P1 genes of strains FH
and TW7-5 are well conserved. It was apparent that the major difference
between the P1 gene sequences was between nucleotides 3633 and 3894 of
the group I P1 gene. This corresponds to positions 3657 through 3918 of
the group II P1 gene (Fig. 2). In this
region, the nucleotide sequence of the M. pneumoniae 309 P1
gene was 9 bp shorter than in either the M129 or TW7-5 strain of
M. pneumoniae. Loss of two HaeIII sites was also
found in the M. pneumoniae 309 P1 gene. This was the reason
for the generation of an HaeIII restriction fragment from
strain 309 which was 155 bp larger in the PCR-RFLP analysis (Fig. 1B).
The position of this new variable region of M. pneumoniae
309 is distant from the previously reported variable regions known to
differ between group I and II P1 genes (Fig. 1A). This therefore
implies that the variation found in the M. pneumoniae 309 P1
gene represents a genuine new variable sequence not reported previously
in the group I and group II P1 genes. We also sequenced the same region from strains 165, 170, and 199 of M. pneumoniae and found
that these three strains possess sequences identical to those of strain 309 (data not shown). As expected from the RFLP analysis, the other
region of the M. pneumoniae 309 P1 gene sequence was almost identical to that of strain TW7-5. However, the following three point
mutations were identified: 2539 A
G, 2872 G
A, and 2886 A
T.
These point mutations affect neither the HaeIII restriction sites nor the deduced amino acid sequences.
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Identification of RepMP sequences involved in generation of P1 gene sequences of M. pneumoniae 309. To confirm that the sequence variation of the M. pneumoniae 309 P1 gene originated from recombination between a functional P1 gene and RepMP2/3 copies outside of the P1 gene locus, we searched the entire genomic sequence of M. pneumoniae M129. Two RepMP2/3 copies that contain sequences highly homologous to the M. pneumoniae 309 P1 variation were found as a result. These homologous sequences are located at nucleotide positions 77474 to 77738 and 415175 to 415432 of the M. pneumoniae M129 genome sequence (GenBank accession no. U00089) (8). Figure 4 shows a comparison of the variable region of the M. pneumoniae 309 P1 gene with these homologous sequences found in the M. pneumoniae M129 genome. In comparison with the two homologous sequences, a 12-bp deletion was observed in the M. pneumoniae 309 P1 gene. Except for this 12-bp deletion, the homologous sequence that exists in nucleotides 77474 through 77738 of M. pneumoniae M129 showed only one nucleotide mismatch with the M. pneumoniae 309 P1 gene sequence (nucleotide 77543), as illustrated in Fig. 4A. This sequence is henceforth designated RepMP2/3-5. On the other hand, the RepMP2/3 sequence that exists within nucleotides 415175 through 415432 of the M. pneumoniae M129 genome showed four single mismatches, and a region upstream from nucleotide 415174 did not match the M. pneumoniae 309 P1 sequence. This is illustrated in Fig. 4B. This sequence is henceforth designated RepMP2/3-6.
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Sequence analysis of the RepMP2/3-5 and RepMP2/3-6 regions from M. pneumoniae 309. In homologous recombination events, DNA sequence exchange by crossover is frequently observed between recombinant DNA strands. Thus, the generation of new P1 gene sequences by homologous recombination may cause shuffling of the RepMP sequences in the M. pneumoniae genome. If the RepMP2/3-5 or RepMP2/3-6 sequence was involved in the homologous recombination that generated the new P1 gene, it is possible that some sequence change would have been made in the RepMP2/3-5 or RepMP2/3-6 region of M. pneumoniae 309 relative to that of M129. Therefore, to investigate this we analyzed the nucleotide sequences of the RepMP2/3-5 and RepMP2/3-6 regions of M. pneumoniae 309. Oligonucleotide PCR primers were designed based on the nonrepetitive sequences flanking the RepMP2/3-5 and RepMP2/3-6 regions of M. pneumoniae M129 and were used to amplify the genomic DNA of strain 309. DNA fragments with the expected sizes, namely, a 2.2-kb fragment containing the RepMP2/3-5 region and a 1.75-kb fragment containing the RepMP2/3-6 region, were specifically amplified by PCR from genomic DNA of M. pneumoniae 309. These fragments were then cloned into Bluescript II SK+ plasmids. Unexpectedly, as a result of this sequencing, we established that the nucleotide sequences of the RepMP2/3-5 and RepMP2/3-6 regions from M. pneumoniae 309 are identical to those from M. pneumoniae M129.
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DISCUSSION |
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It has been reported that the gene coding for the cytadhesin protein P1 of M. pneumoniae contains sequences that exist as multiple copies in the genome. It was suggested that recombination between the P1 gene and repetitive sequences outside the P1 gene could generate a large number of antigenic variations that enable M. pneumoniae to escape from host immune responses (2, 27, 30). A similar feature has also been reported for P1-like cytadhesin genes of Mycoplasma genitalium (3) and Mycoplasma pirum (32). In the case of M. genitalium, the function of repetitive sequences for generating antigenic variants is relatively clear because the polymorphism of the P1-like MgPa gene is observed frequently in clinical isolates. Analysis of the polymorphic sequences of the MgPa genes revealed recombination events between the MgPa gene and such repetitive sequences (22). However, in M. pneumoniae, only two types of P1 gene polymorphism have been identified (groups I and II). There is no direct evidence that clearly explains the role of repetitive sequences in the generation of antigenic variants.
In this study, we precisely analyzed the P1 genes from clinical isolates of M. pneumoniae by using PCR-RFLP methodology and found a new type of P1 gene. Four clinical strains of M. pneumoniae, designated 165, 170, 199, and 309, were found to possess the new type of P1 gene. The novel P1 genes from these four strains were well conserved, although they had been independently isolated from different locations and at different times: strains 165 and 170 were isolated in Kanagawa Prefecture in 1991, strain 199 was also isolated in Kanagawa but in 1993, and strain 309 was isolated in Hokkaido Prefecture in 1998. The different isolation times and locations indicate that the new type of P1 gene sequence is maintained stably in M. pneumoniae cells through generations.
The nucleotide sequence of the new P1 gene is similar to that of the group II P1 gene, but it possesses a sequence variation of approximately 300 bp at the 3' end of the RepMP2/3 region. The location of this variable region does not overlap the previously reported variable region between group I and II P1 genes (Fig. 1A).
Two sequences closely homologous to the variable region of the new P1 gene were found in the M. pneumoniae M129 genome. These two sequences (RepMP2/3-5 and RepMP2/3-6) are part of the RepMP2/3 copies outside the P1 operon. Although when compared with RepMp2/3-5 and RepMP2/3-6 sequences a 12-bp deletion was found in the new P1 gene sequence, these homologous RepMP2/3 copies seem to be the most probable origins of the sequence variation of the M. pneumoniae 309 P1 gene. The M. pneumoniae 309 P1 gene might be created by a homologous recombination event between these RepMP sequences and the P1 gene locus. The gene coding for the RecA-like protein that is required for this homologous recombination has already been reported in the M. pneumoniae genome (8). To investigate this homologous recombination event more clearly, we attempted to analyze the RepMP2/3-5 and RepMP2/-6 regions of M. pneumoniae 309, expecting to find the sequence change made by the recombination. However, this revealed that the nucleotide sequences of the RepMP2/3-5 and RepMP2/-6 regions from M. pneumoniae 309 were identical to those from M. pneumoniae M129. In this attempt, we did not obtain simple evidence for homologous recombination between the P1 gene locus and the RepMp2/3-5 or RepMP2/3-6 sequence of M. pneumoniae 309. One possible explanation of this result is the involvement of gene conversion events. It was reported that the ORF6 gene of the P1 operon also contains a repetitive region (RepMP5) (34) and manifests sequence polymorphism between strains M129 and FH of M. pneumoniae. Ruland et al. analyzed these polymorphic sequences by comparing them with RepMP5 sequences and concluded that the polymorphism of the ORF6 gene might be generated by a gene conversion event (24). This observation on the ORF6 gene is consistent with our findings on the P1 genes and RepMP2/3 sequences of M. pneumoniae M129 and 309 (i.e., unidirectional sequence exchange). Thus, at this point, a gene conversion event is thought to be the most probable mechanism for DNA recombination between the P1 gene locus and the RepMP2/3 copies. This gene conversion would occur through the formation of heteroduplex DNA, which is mediated by RecA-like enzymes and Ruv-like proteins. The genes coding for the RuvA- and RuvB-like proteins have been identified in the M. pneumoniae M129 genome (8).
However, in our sequence comparison analysis, we have no data on the precise number and organization of RepMP copies in the M. pneumoniae 309 genome. M. pneumoniae M129 was identified as a group I P1 gene strain. On the other hand, M. pneumoniae 309 is closely related to group II strains. It is possible that the numbers and organizations of RepMP sequences of both strains may be altered evolutionarily. Therefore, the possibility still remains that other, thus-far-undiscovered RepMP2/3 copies exist in the M. pneumoniae 309 genome and may be involved in homologous recombination with reciprocal sequence exchange. Further investigation will clarify these DNA recombination mechanisms.
The variable region of the predicted amino acid sequence of the new P1 protein corresponds to amino acid positions 1212 to 1298 of the M. pneumoniae M129 P1 protein. This region is relatively close to previously reported epitopes recognized by cytadherence-inhibiting anti-P1 monoclonal antibodies (5, 7). Although the biological effects of such amino acid sequence changes on the function of P1 protein have not yet been examined, it may be that these alterations modulate the interaction of M. pneumoniae with the host immune system.
In this study, we have identified a new type of P1 gene and proposed a possible mechanism for its generation. The existence of a novel type of P1 gene strongly supports the idea that RepMP sequences serve as a reservoir for generation of antigenic variation of P1 cytadhesin genes in M. pneumoniae. Isolation of additional examples of these types of P1 genes and analysis of the organizations of their RepMP sequences will provide a more detailed understanding of the mechanism involved in generation of the P1 gene variation.
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FOOTNOTES |
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* Corresponding author. Mailing address: Department of Safety Research on Biologics, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan. Phone: 81-42-561-0771. Fax: 81-42-565-3315. E-mail: kenri{at}nih.go.jp.
Editor: E. I. Tuomanen
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REFERENCES |
|---|
|
|
|---|
| 1. |
Baseman, J. B.,
R. M. Cole,
D. C. Krause, and D. K. Leith.
1982.
Molecular basis for cytadsorption of Mycoplasma pneumoniae.
J. Bacteriol.
151:1514-1522 |
| 2. | Baseman, J. B., and J. G. Tully. 1997. Mycoplasmas: sophisticated, reemerging, and burdened by their notoriety. Emerg. Infect. Dis. 3:21-32[Medline]. |
| 3. | Dallo, S. F., and J. B. Baseman. 1991. Adhesin gene of Mycoplasma genitalium exists as multiple copies. Microb. Pathog. 10:475-480[Medline]. |
| 4. |
Dallo, S. F.,
J. R. Horton,
C. J. Su, and J. B. Baseman.
1990.
Restriction fragment length polymorphism in the cytadhesin P1 gene of human clinical isolates of Mycoplasma pneumoniae.
Infect. Immun.
58:2017-2020 |
| 5. |
Dallo, S. F.,
C. J. Su,
J. R. Horton, and J. B. Baseman.
1988.
Identification of P1 gene domain containing epitope(s) mediating Mycoplasma pneumoniae cytoadherence.
J. Exp. Med.
167:718-723 |
| 6. | Feldner, J., U. Gobel, and W. Bredt. 1982. Mycoplasma pneumoniae adhesin localized to tip structure by monoclonal antibody. Nature 298:765-767[Medline]. |
| 7. |
GersteneckeR, B., and E. Jacobs.
1990.
Topological mapping of the P1-adhesin of Mycoplasma pneumoniae with adherence-inhibiting monoclonal antibodies.
J. Gen. Microbiol.
136:471-476 |
| 8. |
Himmelreich, R.,
H. Hilbert,
H. Plagens,
E. Pirkl,
B. C. Li, and R. Herrmann.
1996.
Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae.
Nucleic Acids Res.
24:4420-4449 |
| 9. |
Hu, P. C.,
R. M. Cole,
Y. S. Huang,
J. A. Graham,
D. E. Gardner,
A. M. Collier, and W. A. Clyde, Jr.
1982.
Mycoplasma pneumoniae infection: role of a surface protein in the attachment organelle.
Science
216:313-315 |
| 10. |
Hu, P. C.,
A. M. Collier, and J. B. Baseman.
1977.
Surface parasitism by Mycoplasma pneumoniae of respiratory epithelium.
J. Exp. Med.
145:1328-1343 |
| 11. |
Hu, P. C.,
C. H. Huang,
A. M. Collier, and W. A. Clyde, Jr.
1983.
Demonstration of antibodies to Mycoplasma pneumoniae attachment protein in human sera and respiratory secretions.
Infect. Immun.
41:437-439 |
| 12. | Inamine, J. M., T. P. Denny, S. Loechel, U. Schaper, C. H. Huang, K. F. Bott, and P. C. Hu. 1988. Nucleotide sequence of the P1 attachment-protein gene of Mycoplasma pneumoniae. Gene 64:217-229[Medline]. |
| 13. | Inamine, J. M., S. Loechel, and P. C. Hu. 1988. Analysis of the nucleotide sequence of the P1 operon of Mycoplasma pneumoniae. Gene 73:175-183[Medline]. |
| 14. | Jacobs, E. 1991. Mycoplasma pneumoniae virulence factors and the immune response. Rev. Med. Microbiol. 2:83-90. |
| 15. |
Jacobs, E.,
B. Gerstenecker,
B. Mader,
C. H. Huang,
P. C. Hu,
R. Halter, and W. Bredt.
1989.
Binding sites of attachment-inhibiting monoclonal antibodies and antibodies from patients on peptide fragments of the Mycoplasma pneumoniae adhesin.
Infect. Immun.
57:685-688 |
| 16. |
Jacobs, E.,
A. Pilatschek,
B. Gerstenecker,
K. Oberle, and W. Bredt.
1990.
Immunodominant epitopes of the adhesin of Mycoplasma pneumoniae.
J. Clin. Microbiol.
28:1194-1197 |
| 17. | Krause, D. C. 1998. Mycoplasma pneumoniae cytadherence: organization and assembly of the attachment organelle. Trends Microbiol. 6:15-18[Medline]. |
| 18. | Krause, D. C. 1996. Mycoplasma pneumoniae cytadherence: unravelling the tie that binds. Mol. Microbiol. 20:247-253[Medline]. |
| 19. |
Krause, D. C., and J. B. Baseman.
1983.
Inhibition of Mycoplasma pneumoniae hemadsorption and adherence to respiratory epithelium by antibodies to a membrane protein.
Infect. Immun.
39:1180-1186 |
| 20. |
Krause, D. C.,
D. K. Leith, and J. B. Baseman.
1983.
Reacquisition of specific proteins confers virulence in Mycoplasma pneumoniae.
Infect. Immun.
39:830-836 |
| 21. |
Leith, D. K.,
L. B. Trevino,
J. G. Tully,
L. B. Senterfit, and J. B. Baseman.
1983.
Host discrimination of Mycoplasma pneumoniae proteinaceous immunogens.
J. Exp. Med.
157:502-514 |
| 22. |
Peterson, S. N.,
C. C. Bailey,
J. S. Jensen,
M. B. Borre,
E. S. King,
K. F. Bott, and C. A. Hutchison, III.
1995.
Characterization of repetitive DNA in the Mycoplasma genitalium genome: possible role in the generation of antigenic variation.
Proc. Natl. Acad. Sci. USA
92:11829-11833 |
| 23. |
Razin, S., and E. Jacobs.
1992.
Mycoplasma adhesion.
J. Gen. Microbiol.
138:407-422 |
| 24. |
Ruland, K.,
R. Himmelreich, and R. Herrmann.
1994.
Sequence divergence in the ORF6 gene of Mycoplasma pneumoniae.
J. Bacteriol.
176:5202-5209 |
| 25. |
Ruland, K.,
R. Wenzel, and R. Herrmann.
1990.
Analysis of three different repeated DNA elements present in the P1 operon of Mycoplasma pneumoniae: size, number and distribution on the genome.
Nucleic Acids Res.
18:6311-6317 |
| 26. | Sasaki, T., T. Kenri, N. Okazaki, M. Iseki, R. Yamashita, M. Shintani, Y. Sasaki, and M. Yayoshi. 1996. Epidemiological study of Mycoplasma pneumoniae infections in Japan based on PCR-restriction fragment length polymorphism of the P1 cytadhesin gene. J. Clin. Microbiol. 34:447-449[Abstract]. |
| 27. |
Su, C. J.,
A. Chavoya, and J. B. Baseman.
1988.
Regions of Mycoplasma pneumoniae cytadhesin P1 structural gene exist as multiple copies.
Infect. Immun.
56:3157-3161 |
| 28. |
Su, C. J.,
A. Chavoya,
S. F. Dallo, and J. B. Baseman.
1990.
Sequence divergency of the cytadhesin gene of Mycoplasma pneumoniae.
Infect. Immun.
58:2669-2674 |
| 29. |
Su, C. J.,
S. F. Dallo, and J. B. Baseman.
1990.
Molecular distinctions among clinical isolates of Mycoplasma pneumoniae.
J. Clin. Microbiol.
28:1538-1540 |
| 30. |
Su, C. J.,
S. F. Dallo,
A. Chavoya, and J. B. Baseman.
1993.
Possible origin of sequence divergence in the P1 cytadhesin gene of Mycoplasma pneumoniae.
Infect. Immun.
61:816-822 |
| 31. |
Su, C. J.,
V. V. Tryon, and J. B. Baseman.
1987.
Cloning and sequence analysis of cytadhesin P1 gene from Mycoplasma pneumoniae.
Infect. Immun.
55:3023-3029 |
| 32. |
Tham, T. N.,
S. Ferris,
E. Bahraoui,
S. Canarelli,
L. Montagnier, and A. Blanchard.
1994.
Molecular characterization of the P1-like adhesin gene from Mycoplasma pirum.
J. Bacteriol.
176:781-788 |
| 33. |
Ursi, D.,
M. Ieven,
H. van Bever,
W. Quint,
H. G. Niesters, and H. Goossens.
1994.
Typing of Mycoplasma pneumoniae by PCR-mediated DNA fingerprinting.
J. Clin. Microbiol.
32:2873-2875 |
| 34. |
Wenzel, R., and R. Herrmann.
1988.
Repetitive DNA sequences in Mycoplasma pneumoniae.
Nucleic Acids Res.
16:8337-8350 |
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