This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hussain, H.
Right arrow Articles by Allan, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hussain, H.
Right arrow Articles by Allan, E.

 Previous Article  |  Next Article 

Journal of Bacteriology, February 2006, p. 1628-1632, Vol. 188, No. 4
0021-9193/06/$08.00+0     doi:10.1128/JB.188.4.1628-1632.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A Eukaryotic-Type Serine/Threonine Protein Kinase Is Required for Biofilm Formation, Genetic Competence, and Acid Resistance in Streptococcus mutans

Haitham Hussain,1 Pavel Branny,2 and Elaine Allan1*

Division of Microbial Diseases, UCL Eastman Dental Institute, University College London, London, United Kingdom,1 Cell and Molecular Microbiology Division, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic2

Received 30 September 2005/ Accepted 22 November 2005


arrow
ABSTRACT
 
We report an operon encoding a eukaryotic-type serine/threonine protein kinase (STPK) and its cognate phosphatase (STPP) in Streptococcus mutans. Mutation of the gene encoding the STPK produced defects in biofilm formation, genetic competence, and acid resistance, determinants important in caries pathogenesis.


arrow
TEXT
 
Streptococcus mutans is the principal etiological agent of human dental caries (7). Virulence properties include its ability to grow in the mixed-species biofilm known as dental plaque on tooth surfaces (14, 33) and its ability to tolerate low pH (29). Genetic competence is also thought to be important for survival in the oral cavity, as it promotes genome plasticity and therefore adaptation to changing environments.

Several genes with regulatory roles in biofilm formation, acid tolerance, and genetic competence are known, including the HK11/RR11 and VicRK two-component regulatory systems (17, 30), the histidine kinase CiaH (27), the response regulator TarC (11), trigger factor RopA (32), and the ComCDE quorum-sensing system (5, 15, 16, 18).

Protein phosphorylation is an important mechanism used to translate extracellular signals into cellular responses and is carried out by coupled protein kinases and phosphatases. Although serine/threonine protein kinases (STPK) and their associated phosphatases (STPP) have been known for some time to play major regulatory roles in eukaryotes, their discovery in prokaryotes is relatively recent (13, 22, 31). Eukaryotic-type STPK and STPP have been identified in several bacteria, and some possess multiple kinases and/or phosphatases (3, 12, 25). In gram-positive bacteria, STPK and/or STPP has been found in Bacillus subtilis (20), Listeria monocytogenes (2), Streptococcus pneumoniae (6, 24), Streptococcus agalactiae (28), and Streptococcus pyogenes (4). The S. pneumoniae and S. agalactiae STPK are required for virulence in animal models, and the S. pneumoniae enzyme is required for genetic competence (6, 28).

Identification of STPK- and STPP-encoding genes. Analysis of the genome sequence (1) identified pknB (NC_004350; GeneID 1029535), encoding a homologue of the eukaryotic-like STPK family. The highest similarity is with STPK of S. pyogenes (NCBI accession no. AAM79976; 63% identity), S. agalactiae (AAM99225; 59% identity), and S. pneumoniae (AAM47530; 51% identity) and is most pronounced in the N-terminal region containing the consensus Hanks' subdomains that comprise the catalytic domain (8, 9). Downstream of the kinase domain is a hydrophobic region that may be a transmembrane domain. Topology analysis (http://www.ch.embnet.org/software/TMPRED_form.html) predicts that PknB is an N-in, C-out membrane protein with the catalytic domain in the cytoplasm and the C-terminal, presumably sensory, domain located extracellularly. The SMART software (http://smart.embl-heidelberg.de/) predicts three tandem PASTA (penicillin-binding protein- and serine/threonine kinase-associated) domains (34) in the C terminus. The PASTA domain is thought to bind ß-lactam antibiotics and their peptidoglycan analogues, suggesting that PknB may sense unlinked peptidoglycan (34).

pknB is located downstream of, and overlaps with, pppL (GeneID 1027981), a gene predicted to encode an STPP of the 2C subfamily (Prosite entry PDOC00792) that is most closely related to the S. pyogenes enzyme (AAM79977; 73% identity). The presence of a consensus promoter sequence (Fig. 1) within the gene preceding pppL and a transcriptional terminator following pknB suggested that pknB and pppL are cotranscribed, and this was confirmed by reverse transcription-PCR (data not shown). The proximity of the hk11/rr11 gene pair encoding a two-component regulatory system involved in biofilm formation and acid resistance (17) is interesting, as STPK genes are sometimes adjacent to genes encoding their substrates (21, 23).


Figure 1
View larger version (7K):
[in this window]
[in a new window]
  		FIG. 1. Physical map of the pppL/pknB locus. Thick arrows denote open reading frames. Putative promoter and terminator regions are represented as P and T, respectively. Genes were assigned putative functions based on high BLAST scores with known proteins (accession numbers of the closest orthologues in parentheses): 1, guanylate kinase (AAM79982); 2, RNA polymerase omega subunit (AAM79981); 3, primosomal replication factor Y (AAK34400); 4, methionyl tRNA formyltransferase (AAK34399); 5, rRNA methyltransferase (AAT87518); 6, conserved hypothetical protein (AAM79975); 7, peptidyl-prolyl cis-trans isomerase (AAK75626); 8, polyribonucleotide nucleotidyltransferase (general stress protein 13) (AAK34392).

Construction and complementation of a pknB mutant. pknB and flanking DNA were PCR amplified from strain UA159 and cloned into pGEM-T-Easy (Table 1). A 1.7-kb fragment of pknB was deleted, and a unique SmaI site was introduced by inverse PCR (Table 1) and used to clone a kanamycin resistance gene (aphA3), producing pEA72. The insert was released from pEA72 and transformed into UA159 as a linear fragment. Allelic replacement was confirmed by PCR using primers flanking pknB (data not shown).


View this table:
[in this window]
[in a new window]
  		TABLE 1. Oligonucleotides, strains, and plasmids useda

pVA838 (19) was used to make two constructs for complementation: pEA78, containing pknB regulated by the erythromycin resistance gene promoter (Perm) from pVA838, and pEA74, identical to pEA78 except that it lacked a ribosome binding site for pknB. Transformation (10) of the pknB mutant (PKNB) with pEA74 and pEA78 yielded a single Ermr colony in each case.

The pknB mutant has a reduced early growth rate. Comparison of the growth of strains PKNB and UA159 in brain heart infusion (BHI) broth showed that PKNB had a reduced growth rate early in the growth cycle, but by exponential phase the growth rate of PKNB was not significantly different from that of UA159 (data not shown). As the mutant had a tendency to clump, cultures were vortexed before removal of samples for optical density (OD) measurement. After overnight culture in tryptone soy broth containing 0.5% (wt/vol) yeast extract, UA159 grew as a uniformly turbid suspension, whereas PKNB accumulated at the bottom of the culture vessel (data not shown). Interestingly, aggregation of PKNB was less apparent in BHI broth (data not shown). Both defects were partially restored by complementation in strain PKNBC1, whereas PKNBC2 exhibited similar growth kinetics and a propensity to aggregate in the same way as PKNB.

The pknB mutant has a transformation defect. pVA838 (19) or genomic DNA from a spontaneous streptomycin-resistant (Strr) strain of UA159, each at 1 µg/ml, was used to measure transformation (10) (Table 2). To eliminate the possibility that the transformation defect was a result of the reduced growth rate of PKNB, assays were carried out that ensured that PKNB and UA159 had reached the same density (OD at 600 nm [OD600], 0.2) before DNA addition. These assays gave results similar to those in Table 2 (not shown). Addition of synthetic competence-stimulating peptide (500 ng/ml; Sigma-Genosys Ltd.) (18) did not improve the transformation efficiency of PKNB, whereas UA159 showed a 10-fold increase (data not shown). Reintroduction of pknB on a plasmid in PKNBC1 resulted in a transformation frequency 100-fold greater than that of the parent (Table 2), presumably as a result of the increased gene dosage. PKNBC2 gave similar levels of transformation as PKNB.


View this table:
[in this window]
[in a new window]
  		TABLE 2. Transformability of strains tested using pVA838 or Strr genomic DNA

Mutation of pknB results in defects in biofilm formation. Biofilms were grown on hydroxyapatite disks in 24-well culture clusters (Corning Inc., from Fisher Scientific, Loughborough, United Kingdom). Two milliliters of undiluted and diluted (1:50) exponential-phase culture (OD600, ~0.5) in BHI broth was added to the wells containing the hydroxyapatite disks. After incubation for 48 h the disks were rinsed, treated with BacLight LIVE/DEAD stain (Molecular Probes), and visualized by confocal laser scanning microscopy (35). Marked differences in biofilm depth and coverage were apparent between the mutant and parent biofilms (Fig. 2). The parent strain produced a thicker biofilm (typically around 28 µm) than the mutant (typically around 13 µm) and produced more biomass. The structure of the parent biofilm is typical of a mature oral biofilm (26), comprising areas covered by stacks and areas with little or no coverage that form channels between the regions of biomass. The mutant produced smaller stacks and clusters with less coverage and more intercellular gaps, more typical of a biofilm during early development. The reduced biofilm density in PKNB is not due to its reduced early growth rate, as prolonged incubation did not result in an increase in biofilm density. In PKNBC1, biofilm density was restored to approximately 70% that of the parent biofilm (data not shown). The fact that PKNBC1 showed only a partial restoration of the biofilm defect whereas it gave levels of transformation greater than the parent is presumably due to perturbation of the STPK-controlled signal transduction pathways that results from overexpression of pknB on a multicopy plasmid.


Figure 2
View larger version (91K):
[in this window]
[in a new window]
  		FIG. 2. Confocal laser scanning microscopy images of biofilm that developed on hydroxyapatite disks by S. mutans UA159 (A) and S. mutans PKNB (B). The intersecting lines indicate the position of the sagittal section (side panels). Dimensions of the region displayed are 167 by 167 µm (x-y perspective; square panel) and 167 by 28 µm (x-z perspective; rectangular panel). The images shown are representative of the biofilms after 24 h of growth.

The pknB mutant is sensitive to low pH. The abilities of UA159 and its derivatives to grow at low pH were examined by growing them on agar adjusted to pH 5.0 (17). Compared to the parent, PKNB showed reduced growth on pH 5.0 agar, whereas it grew as well as the parent on agar at pH 7.0. PKNBC1 grew as well as the parent at both pH 5.0 and pH 7.0 (Fig. 3).


Figure 3
View larger version (52K):
[in this window]
[in a new window]
  		FIG. 3. Effect of pH on the growth of S. mutans strains UA159, PKNB, and PKNBC1.

Summary. Disruption of pknB, encoding a eukaryotic-type STPK in S. mutans, causes defects in biofilm formation, acid resistance, and genetic competence. Other genes with regulatory roles in these phenotypes are known, raising the possibility that the defects in the pknB mutant are the result of altered expression or activity of one or more of these proteins.


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: Division of Microbial Diseases, UCL Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, United Kingdom. Phone: 44(0)20 7915 1256. Fax: 44(0)20 7915 1127. E-mail: e.allan{at}eastman.ucl.ac.uk. Back


arrow
REFERENCES
 
    1
  1. Ajdic, D., W. M. McShan, R. E. McLaughlin, G. Savic, J. Chang, M. B. Carson, C. Primeaux, R. Tian, S. Kenton, H. Jia, S. Lin, Y. Qian, S. Li, H. Zhu, F. Najar, H. Lai, J. White, B. A. Roe, and J. J. Ferretti. 2002. Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen. Proc. Natl. Acad. Sci. USA 99:14434-14439.[Abstract/Free Full Text]
    2. 2
  2. Archambaud, C., E. Gouin, J. Pizzaro-Cerda, P. Cossart, and O. Dussurget. 2005. Translation elongation factor EF-Tu is a target for Stp, a serine-threonine phosphatase involved in virulence of Listeria monocytogenes. Mol. Microbiol. 56:383-396.[CrossRef][Medline]
    3. 3
  3. Av-Gay, Y., and M. Everett. 2000. The eukaryotic-like serine/threonine protein kinases of Mycobacterium tuberculosis. Trends Microbiol. 8:238-244.[CrossRef][Medline]
    4. 4
  4. Beres, S. B., G. L. Sylva, K. D. Barbian, B. Lei, J. S. Hoff, N. D. Mammarella, M.-Y. Liu, J. C. Smoot, S. F. Porcella, L. D. Parkins, J. K. McCormick, D. Y. M. Leung, P. M. Schlievert, and J. M. Musser. 2002. Genome sequence of a serotype M3 strain of group A Streptococcus: phage-encoded toxins, the high-virulence phenotype, and clone emergence. Proc. Natl. Acad. Sci. USA 99:10078-10083.[Abstract/Free Full Text]
    5. 5
  5. Cvitkovitch, D. G. 2001. Genetic competence and transformation in oral streptococci. Crit. Rev. Oral Biol. Med. 12:217-243.[Abstract/Free Full Text]
    6. 6
  6. Echenique, J., A. Kadioglu, S. Romao, P. W. Andrew, and M.-C. Trombe. 2004. Protein serine/threonine kinase StkP positively controls virulence and competence in Streptococcus pneumoniae. Infect. Immun. 72:2434-2437.[Abstract/Free Full Text]
    7. 7
  7. Hamada, S., and H. D. Slade. 1980. Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol. Rev. 44:331-384.[Free Full Text]
    8. 8
  8. Hanks, S. K., A. M. Quinn, and T. Hunter. 1988. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241:42-52.[Abstract/Free Full Text]
    9. 9
  9. Hanks, S. K., and T. Hunter. 1995. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J. 9:576-596.[Abstract]
    10. 10
  10. Hudson, M. C., and R. Curtiss III. 1990. Regulation of expression of Streptococcus mutans genes important to virulence. Infect. Immun. 58:464-470.[Abstract/Free Full Text]
    11. 11
  11. Idone, V., S. Brendtro, R. Gillespie, S. Kocaj, E. Peterson, M. Rendi, W. Warren, S. Michalek, K. Krastel, D. Cvitkovitch, and G. Spatafora. 2003. Effect of an orphan response regulator on Streptococcus mutans sucrose-dependent adherence and cariogenesis. Infect. Immun. 71:4351-4360.[Abstract/Free Full Text]
    12. 12
  12. Inouye, S., R. Jain, T. Ueki, H. Nariya, C. Y. Xu, M. Y. Hsu, B. A. Fernandez-Luque, J. Munoz-Dorado, E. Farez-Vidal, and M. Inouye. 2000. A large family of eukaryotic-like protein Ser/Thr kinases of Myxococcus xanthus, a developmental bacterium. Microb. Comp. Genomics 5:103-120.[CrossRef][Medline]
    13. 13
  13. Kennelly, P. J., and M. Potts. 1996. Fancy meeting you here. A fresh look at "prokaryotic" protein phosphorylation. J. Bacteriol. 178:4759-4764.[Abstract/Free Full Text]
    14. 14
  14. Kuramitsu, H. K. 1993. Virulence factors of mutans streptococci: role of molecular genetics. Crit. Rev. Oral Biol. Med. 4:159-176.[Abstract/Free Full Text]
    15. 15
  15. Li, Y.-H., M. N. Hanna, G. Svensäter, R. P. Ellen, and D. G. Cvitkovitch. 2001. Cell density modulates acid adaptation in Streptococcus mutans: implications for survival in biofilms. J. Bacteriol. 183:6875-6884.[Abstract/Free Full Text]
    16. 16
  16. Li, Y.-H., P. C. Lau, J. H. Lee, R. P. Ellen, and D. G. Cvitkovitch. 2001. Natural genetic transformation of Streptococcus mutans growing in biofilms. J. Bacteriol. 183:897-908.[Abstract/Free Full Text]
    17. 17
  17. Li, Y.-H., P. C. Lau, N. Tang, G. Svensäter, R. P. Ellen, and D. G. Cvitkovitch. 2002. Novel two-component regulatory system involved in biofilm formation and acid resistance in Streptococcus mutans. J. Bacteriol. 184:6333-6342.[Abstract/Free Full Text]
    18. 18
  18. Li, Y.-H., N. Tang, M. B. Aspiras, P. C. Y. Lau, J. H. Lee, R. P. Ellen, and D. G. Cvitkovitch. 2002. A quorum-sensing signaling system essential for genetic competence in Streptococcus mutans is involved in biofilm formation. J. Bacteriol. 184:2699-2708.[Abstract/Free Full Text]
    19. 19
  19. Macrina, F. L., J. A. Tobian, K. R. Jones, R. P. Evans, and D. B. Clewell. 1982. A cloning vector able to replicate in Escherichia coli and Streptococcus sanguis. Gene 19:345-353.[CrossRef][Medline]
    20. 20
  20. Madec, E., A. Laszkiewicz, A. Iwanicki, M. Obuchowski, and S. Seror. 2002. Characterization of a membrane-linked Ser-Thr protein kinase in Bacillus subtilis, implicated in developmental processes. Mol. Microbiol. 46:571-586.[CrossRef][Medline]
    21. 21
  21. Molle, V., L. Kremer, C. Girard-Blanc, G. S. Besra, A. J. Cozzone, and J. F. Prost. 2003. An FHA phosphoprotein recognition domain mediates protein EmbR phosphorylation by PknH, a Ser/Thr protein kinase from Mycobacterium tuberculosis. Biochemistry 42:15300-15309.[CrossRef][Medline]
    22. 22
  22. Munoz-Dorado, J., S. Inouye, and M. Inouye. 1991. A gene encoding a protein serine/threonine kinase is required for normal development of M. xanthus, a gram-negative bacterium. Cell 67:995-1006.[CrossRef][Medline]
    23. 23
  23. Nariya, H., and S. Inouye. 2002. Activation of 6-phosphofructokinase via phosphorylation by Pkn4, a protein Ser/Thr kinase of Myxococcus xanthus. Mol. Microbiol. 46:1353-1366.[CrossRef][Medline]
    24. 24
  24. Nováková, L., L. Sasková, P. Pallová, J. Janeèek, J. Novotná, A. Ulrych, J. Echenique, M.-C. Trombe, and P. Branny. 2005. Characterization of a eukaryotic type serine/threonine protein kinase and protein phosphatase of Streptococcus pneumoniae and identification of kinase substrates. FEBS J. 272:1243-1254.[CrossRef][Medline]
    25. 25
  25. Petricková, K., and M. Petricek. 2003. Eukaryotic-type protein kinases in Streptomyces coelicolor: variations on a common theme. Microbiology 149:1609-1621.[Abstract/Free Full Text]
    26. 26
  26. Pratten, J., C. S. Andrews, D. Q. M. Craig, and M. Wilson. 2000. Structural studies of microcosm dental plaques grown under different nutritional conditions. FEMS Microbiol. Lett. 189:215-218.[CrossRef][Medline]
    27. 27
  27. Qi, F., J. Merritt, R. Lux, and W. Shi. 2004. Inactivation of the ciaH gene in Streptococcus mutans diminishes mutacin production and competence development, alters sucrose-dependent biofilm formation, and reduces stress tolerance. Infect. Immun. 72:4895-4899.[Abstract/Free Full Text]
    28. 28
  28. Rajagopal, L., A. Clancy, and C. E. Rubens. 2003. A eukaryotic type serine/threonine kinase and phosphatase in Streptococcus agalactiae reversibly phosphorylate an inorganic pyrophosphatase and affect growth, cell segregation, and virulence. J. Biol. Chem. 278:14429-14441.[Abstract/Free Full Text]
    29. 29
  29. Sansone, C., J. van Houte, K. Joshipura, R. Kent, and H. C. Margolis. 1993. The association of mutans streptococci and non-mutans streptococci capable of acidogenesis at a low pH with dental caries on enamel and root surfaces. J. Dent. Res. 72:508-516.[Abstract/Free Full Text]
    30. 30
  30. Senadheera, M. D., B. Guggenheim, G. A. Spatafora, Y.-C. Huang, J. Choi, D. C. I. Hung, J. S. Treglown, S. D. Goodman, R. P. Ellen, and D. G. Cvitkovitch. 2005. A VicRK signal transduction system in Streptococcus mutans affects gtfBCD, gbpB, and ftf expression, biofilm formation, and genetic competence development. J. Bacteriol. 187:4064-4076.[Abstract/Free Full Text]
    31. 31
  31. Shi, L., M. Potts, and P. J. Kennelly. 1998. The serine, threonine, and/or tyrosine-specific protein kinases and protein phosphatases of prokaryotic organisms: a family portrait. FEMS Microbiol. Rev. 22:229-253.[CrossRef][Medline]
    32. 32
  32. Wen, Z. T., P. Suntharaligham, D. G. Cvitkovitch, and R. A. Burne. 2005. Trigger factor in Streptococcus mutans is involved in stress tolerance, competence development, and biofilm formation. Infect. Immun. 73:219-225.[Abstract/Free Full Text]
    33. 33
  33. Yamashita, Y., W. H. Bowen, R. A. Burne, and H. K. Kuramitsu. 1993. Role of the Streptococcus mutans gtf genes in caries induction in the specific-pathogen-free rat model. Infect. Immun. 61:3811-3817.[Abstract/Free Full Text]
    34. 34
  34. Yeats, C., R. D. Finn, and A. Bateman. 2002. The PASTA domain: a ß-lactam-binding domain. Trends Biochem. Sci. 27:438-440.[CrossRef][Medline]
    35. 35
  35. Zanin, I. C. J., R. B. Goncalves, A. B. Junior, C. K. Hope, and J. Pratten. 2005. Susceptibility of Streptococcus mutans biofilms to photodynamic therapy: an in vitro study. J. Antimicrob. Chemother. 56:324-330.[Abstract/Free Full Text]

Journal of Bacteriology, February 2006, p. 1628-1632, Vol. 188, No. 4
0021-9193/06/$08.00+0     doi:10.1128/JB.188.4.1628-1632.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Donat, S., Streker, K., Schirmeister, T., Rakette, S., Stehle, T., Liebeke, M., Lalk, M., Ohlsen, K. (2009). Transcriptome and Functional Analysis of the Eukaryotic-Type Serine/Threonine Kinase PknB in Staphylococcus aureus. J. Bacteriol. 191: 4056-4069 [Abstract] [Full Text]  
  • Debarbouille, M., Dramsi, S., Dussurget, O., Nahori, M.-A., Vaganay, E., Jouvion, G., Cozzone, A., Msadek, T., Duclos, B. (2009). Characterization of a Serine/Threonine Kinase Involved in Virulence of Staphylococcus aureus. J. Bacteriol. 191: 4070-4081 [Abstract] [Full Text]  
  • Suntharalingam, P., Senadheera, M. D., Mair, R. W., Levesque, C. M., Cvitkovitch, D. G. (2009). The LiaFSR System Regulates the Cell Envelope Stress Response in Streptococcus mutans. J. Bacteriol. 191: 2973-2984 [Abstract] [Full Text]  
  • Beltramini, A. M., Mukhopadhyay, C. D., Pancholi, V. (2009). Modulation of Cell Wall Structure and Antimicrobial Susceptibility by a Staphylococcus aureus Eukaryote-Like Serine/Threonine Kinase and Phosphatase. Infect. Immun. 77: 1406-1416 [Abstract] [Full Text]  
  • Hasegawa, Y., Tribble, G. D., Baker, H. V., Mans, J. J., Handfield, M., Lamont, R. J. (2008). Role of Porphyromonas gingivalis SerB in Gingival Epithelial Cell Cytoskeletal Remodeling and Cytokine Production. Infect. Immun. 76: 2420-2427 [Abstract] [Full Text]  
  • Merritt, J., Zheng, L., Shi, W., Qi, F. (2007). Genetic characterization of the hdrRM operon: a novel high-cell-density-responsive regulator in Streptococcus mutans. Microbiology 153: 2765-2773 [Abstract] [Full Text]  
  • Saskova, L., Novakova, L., Basler, M., Branny, P. (2007). Eukaryotic-Type Serine/Threonine Protein Kinase StkP Is a Global Regulator of Gene Expression in Streptococcus pneumoniae. J. Bacteriol. 189: 4168-4179 [Abstract] [Full Text]  
  • Kristich, C. J., Wells, C. L., Dunny, G. M. (2007). A eukaryotic-type Ser/Thr kinase in Enterococcus faecalis mediates antimicrobial resistance and intestinal persistence. Proc. Natl. Acad. Sci. USA 104: 3508-3513 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hussain, H.
Right arrow Articles by Allan, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hussain, H.
Right arrow Articles by Allan, E.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»