• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jbacterPermissionsJournals.ASM.orgJournalJB ArticleJournal InfoAuthorsReviewers
J Bacteriol. Apr 2008; 190(8): 2645–2648.
Published online Feb 1, 2008. doi:  10.1128/JB.01682-07
PMCID: PMC2293224

Essentiality, Bypass, and Targeting of the YycFG (VicRK) Two-Component Regulatory System in Gram-Positive Bacteria[down-pointing small open triangle]

Bacterial two-component systems and phosphorelays are woven into the fabric of cellular regulatory mechanisms ensuring homeostatic equilibrium under a wide variety of environmental conditions (reviewed in references 13, 15, 18, 19, 23, and 28). Of the individual two-component regulatory systems (TCSs), YycFG has excited interest for several reasons and has been the topic of many recent studies. The YycFG system appears to be essential for growth in most bacterial species that encode it (10, 17, 27, 48). The essentiality may be linked to its control of murein biosynthesis (1, 3, 6, 7, 21, 26, 32, 33), cell division (10, 12, 21), lipid integrity (3, 27, 29, 33), exopolysaccharide biosynthesis and biofilm formation (1, 2, 6, 39, 41), and virulence factor expression (2, 6, 24, 26, 33, 39). Because of these effects on essential functions and the fact that the YycFG TCS is widely conserved in low-GC gram-positive bacteria, including several major pathogens, it has been considered a potential target for anti-infective therapeutics (see, e.g., references 14, 25, 35-37, and 42).

Interestingly, the YycFG TCS regulates different sets of genes in different bacterial species to coordinate and control the disparate, yet related, vital functions listed above (3, 6, 29, 33). The signals sensed by the YycFG TCS to maintain cell surface and murein homeostasis are largely unknown; however, the YycFG TCS seems to be one of few TCSs that integrate signals through physiologically relevant cross talk. The best-studied example of cross talk in this system is between YycFG and the PhoPR phosphate limitation TCS in Bacillus subtilis (21, 22). In addition, the YycFG TCS includes several auxiliary proteins in its complex regulatory circuits, making it in fact at least a four-component regulatory system in some bacterial species (34, 45, 46). However, recent studies have shown that there are instances where the YycFG TCS appears not to be essential in some bacterial systems (see below) (11, 26, 32). Such results have brought into question the value of TCSs in general and YycFG in particular as therapeutic targets. We argue here that instances of YycFG nonessentiality may be due to genetic bypass mechanisms, and their existence does not diminish the importance of the YycFG TCS in bacterial physiology and pathogenesis or the potential of this TCS and other TCSs from serving as targets for antibiotic development. Furthermore, the real benefit that has emerged from studying the YycFG TCS across species is the realization that this type of TCS may be integrated into higher-order homeostatic regulatory mechanisms with common goals in all gram-positive species despite the disparate gene targets in each.

The core of the YycFG TCS consists of the YycG histidine kinase and the YycF response regulator (Fig. (Fig.1).1). Because this TCS was discovered independently in different bacterial species, there are several different names for it. However, the YycFG designation from B. subtilis has been widely used in many papers for bacterial species other than Streptococcus, where YycFG are designated VicRK (Fig. (Fig.1).1). The different names for the YycG and VicK histidine kinases coincide with different structural features (34, 45, 46, 48) (Fig. (Fig.1).1). In non-Streptococcus species such as B. subtilis, Staphylococcus aureus, and Enterococcus faecalis, YycG contains a large extracellular domain between two transmembrane domains (10, 16, 27). In contrast, VicK from Streptococcus-related species is generally anchored to the cell membrane by a single transmembrane domain (34, 48). Exceptions such as VicK from Lactococcus lactis contain two transmembrane domains but still lack an extracellular domain. The YycG and VicK histidine kinases contain similar HAMP- and PAS-sensing domains along with the dimerization/histidine phosphotransfer (HisKA) and kinase catalytic (HATPase) domains found in other histidine kinases (Fig. (Fig.1)1) (reviewed in references 23 and 28). In contrast to the YycG and VicK histidine kinases, the amino acid sequences of the receiver and effector domains of YycF and VicR are highly conserved and belong to the OmpR family of response regulators (reviewed in references 13 and 43).

FIG. 1.
Arrangements of genes in the operons encoding the essential YycFG, VicRK, and MtrAB TCSs, domains in the YycG, VicK, and MtrB histidine kinases, and cellular locations of proteins. The operons are drawn to scale from representative species, Bacillus subtilis ...

In most parent strains studied to date, the gene encoding the YycF (VicR) response regulator cannot be simply knocked out and is essential for growth in rich laboratory media. The exceptions to this generalization are strains that likely contain some form of bypass mutation, as discussed below. In contrast, there is again a dichotomy between the YycG and VicK classes of histidine kinases (Fig. (Fig.1).1). The genes encoding the YycG class of histidine kinase are essential and cannot be knocked out. In contrast, the VicK class appears to be dispensable in different species of Streptococcus (9, 26, 32, 39, 48). Phosphorylation of the VicR response regulator seems to be required for growth (9, 32). This observation implies that cross talk by other histidine kinases or small phosphoryl group donors, such as acetyl phosphate, phosphorylates VicR in deletion mutants lacking VicK. However, this apparent lack of essentiality of vicK can be misinterpreted. The growth properties of ΔvicK mutants have been studied using a relatively limited number of conditions, and it is possible that other conditions that require VicK for growth will be found. In addition, vicK knockout mutants show defects in growth and biofilm formation, increased cell chaining, and reduced virulence in different species of Streptococcus (1, 2, 24, 26, 32, 39). Thus, functional YycG and VicK histidine kinases are required for normal cellular physiology and pathogenesis.

It is possible to bypass the essentiality of the VicRK TCS entirely in some bacterial species. In Streptococcus pneumoniae, the VicRK TCS positively regulates the transcription of several surface proteins and virulence factors (29, 32, 33). Of this group, only the pcsB gene, which encodes a putative hydrolase required for murein biosynthesis and cell division, is essential for growth (31, 32). A synthetic, constitutively expressed promoter fused to pcsB bypasses the requirement for positive regulation by the VicRK TCS, and the gene encoding the VicR response regulator can be deleted (32). However, even modest misregulation resulting in approximately a two- to threefold decrease in the amount of PcsB causes significant defects in cell division, susceptibilities to stress conditions, and virulence (31, 32). In contrast to the case in S. pneumoniae, the essentiality of the YycF response regulator is more complicated and appears to be polygenic in most other bacteria (3, 6). For example, the coregulation of a group of nonessential, partially redundant genes that mediate murein metabolism is essential for normal cell division and growth of B. subtilis (3). In this case, a simple bypassing of YycF function has not been possible to achieve genetically.

There are two other instances in the literature where the YycFG (VicRK) system appears to be nonessential, possibly due to bypass. An insertion of a suicide vector into vicR of Streptococcus pyogenes (group A Streptococcus) could be obtained only at a frequency 3 orders of magnitude lower than that of a control construct (26). Therefore, it seems likely that this mutant contained suppressors that allowed the expression of the essential gene(s) controlled by VicR. Consistent with this interpretation, clean deletion mutations could not be constructed in vicR (26). It is noteworthy that the vicR insertion mutant showed defects in growth, viability, and virulence compared to the parent strain (26). Some of these phenotypes were complemented by a wild-type copy of the vicR gene, but positive complementation does not necessarily rule out the presence of suppressors and indicates that these phenotypes are due to the misregulation of nonessential genes in the VicRK regulon. A second example of the inactivation of this system was reported for a clinical isolate of Staphylococcus aureus following treatment with the lipopeptide antibiotic daptomycin (11). This isolate, which showed increased resistance to daptomycin, contained a single-nucleotide A insertion that caused a frameshift early in yycG. However, clinical and laboratory isolates with decreased susceptibility to daptomycin also contained other mutations, such as lesions in mprF (lysylphosphatidylglycerol synthetase) (11), and it is possible that one of these other mutations contributes to suppression or cross talk that allows YycG function to be bypassed.

The auxiliary proteins of the YycFG (VicRK) TCS also influence its function and apparent essentiality. In all bacteria that contain this TCS, the genes encoding the histidine kinase and response regulator are cotranscribed with a gene encoding a third component, designated YycJ in B. subtilis and most other gram-positive species and VicX in species of Streptococcus (Fig. (Fig.1).1). In addition, except in species of Streptococcus, the yycFG and yycJ genes are cotranscribed with two other genes, designated yycH and yycI, which encode other components of the TCS (Fig. (Fig.1)1) (45-48). Thus, bacteria that contain the YycG or VicK class of histidine kinases potentially contain a five- or three-component system, respectively (34, 45). The YycJ (VicX), YycH, and YycI proteins seem to be dispensable for growth under the limited number of conditions tested so far. The cytoplasmic YycJ (VicX) protein contains a putative metal binding site in a β-lactamase fold (48), but its catalytic function, if any, is unknown. In B. subtilis, YycJ does not seem to be tied to YycFG TCS signaling (45), whereas the VicX protein does seem to play some unspecified role in signaling through the VicRK TCS in species of Streptococcus (32, 40). Considerably more is known about the function and structures of the YycH and YycI proteins, which are membrane bound and contain extracellular domains (41-43) (Fig. (Fig.1).1). Knockout mutations of yycH and yycI were recovered as suppressors that allowed the growth of a temperature-sensitive yycF mutant at a raised, nonpermissive temperature (44-46). A current model for this suppression is that YycHI normally negatively regulate the autophosphorylation of the YycG histidine kinase and that the lack of YycHI leads to the increased phosphorylation of the YycF response regulator in the temperature-sensitive mutant (45). Thus, changes in the functions of the YycHI auxiliary proteins may act to bypass some defects in YycF function. However, to date, this form of bypass is not complete and still requires the partially active YycF response regulator. Additional unlinked genes may also play roles in signal transduction by the YycFG (VicRK) TCS. For example, a recent study suggests some direct or indirect link between the function of the VicRK TCS and the StkP serine/threonine kinase of S. pneumoniae (38).

A broader biological parallelism between the YycFG (VicRK) TCS and a conserved essential TCS in high-GC gram-positive species, such as the Actinobacteria, which include industrially important Streptomyces and medically important Mycobacterium and Corynebacterium species, has emerged. This essential TCS, designated MtrAB (reviewed in reference 20), shares several properties with the YycFG (VicRK) TCSs in low-GC gram-positive species. Similar to the case in Streptococcus, the MtrA response regulator is essential for growth in mycobacteria and possibly Streptomyces, whereas the MtrB histidine kinase is dispensable (5, 20, 49). This situation again suggests the possibility of physiologically relevant cross talk (20). However, the YycG (VicK) and MtrB histidine kinases are not strict orthologues, since MtrB lacks a PAS domain, which is a conserved feature of YycG (VicK) histidine kinases (Fig. (Fig.1).1). Most intriguingly, the MtrAB TCSs play roles in maintaining normal cell division and envelope synthesis (4, 5, 20, 30, 49), parallel to the functions of the YycFG (VicRK) TCSs in low-GC gram-positive species. Even in corynebacteria, where the mtrAB TCS genes can apparently both be knocked out, severe defects in cell morphology result (30), but it is not clear whether a suppressor arose in the ΔmtrAB mutant. The MtrAB TCSs seem to achieve their regulation of cell surface homeostasis by regulating different sets of genes in different species, again paralleling the YycFG (VicRK) TCSs in low-GC gram-positive bacteria. Last, the MtrAB TCS is always genetically associated with a third component, the LpqB lipoprotein of unknown function (Fig. (Fig.1).1). Similar to the YycHI auxiliary proteins in B. subtilis, it has been postulated that LpqB may play roles in signaling to the MtrB histidine kinase (20). Thus, all gram-positive bacteria seem to contain an essential TCS that uses auxiliary proteins to maintain cell wall and surface homeostasis, possibly in response to changes in cellular signals, stress conditions, or both.

The degrees of essentiality of the YycFG (VicRK) and the MtrAB TCSs in different bacteria bring us back to the issue of whether these TCSs are suitable targets for the development of new antibiotics. In one sense, this question has become somewhat misdirected. Putative YycFG (VicRK)-specific inhibitors that have emerged from some screens (see, e.g., references 25, 35, and 37) would prevent the growth of only low-GC gram-positive, but not high-GC gram-positive or gram-negative, bacteria. In addition, there is a high likelihood of a development of resistance to compounds that inhibit a single target, such as the YycF (VicK) histidine kinase. A far more powerful strategy is to find general inhibitors of histidine kinase autophosphorylation or phosphoryl group transfer between cognate histidine kinases and response regulators. Although this has been a largely unfulfilled challenge (13, 14, 42), there are unusual structural features of these classes of proteins, such as the Bergerat ATP-binding fold in histidine kinases, that make this search attractive (8, 14). That said, having an essential TCS as a target does add to the therapeutic potential of a general TCS inhibitor, and the YycFG (VicRK) and MtrAB TCSs remain attractive targets as part of this larger drug discovery effort. As described above, documented and likely cases of bypass of YycFG (VicRK) TCS function result in defective growth and virulence, which underscores the vital role of this and other TCSs in maintaining cell surface homeostasis in all gram-positive species.

Acknowledgments

We thank Kyle Wayne and Krystyna Kazmierczak for critically reading this commentary.

Research in this area is supported by grants NIH AI060744 and NSF 0543289 to M.E.W. and NIH GM19416 to J.A.H.

Notes

The views expressed in this Commentary do not necessarily reflect the views of the journal or of ASM.

Footnotes

[down-pointing small open triangle]Published ahead of print on 1 February 2008.

REFERENCES

1. Ahn, S. J., and R. A. Burne. 2007. Effects of oxygen on biofilm formation and the AtlA autolysin of Streptococcus mutans. J. Bacteriol. 1896293-6302. [PMC free article] [PubMed]
2. Ahn, S. J., Z. T. Wen, and R. A. Burne. 2007. Effects of oxygen on virulence traits of Streptococcus mutans. J. Bacteriol. 1898519-8527. [PMC free article] [PubMed]
3. Bisicchia, P., D. Noone, E. Lioliou, A. Howell, S. Quigley, T. Jensen, H. Jarmer, and K. M. Devine. 2007. The essential YycFG two-component system controls cell wall metabolism in Bacillus subtilis. Mol. Microbiol. 65180-200. [PubMed]
4. Brocker, M., and M. Bott. 2006. Evidence for activator and repressor functions of the response regulator MtrA from Corynebacterium glutamicum. FEMS Microbiol. Lett. 264205-212. [PubMed]
5. Cangelosi, G. A., J. S. Do, R. Freeman, J. G. Bennett, M. Semret, and M. A. Behr. 2006. The two-component regulatory system mtrAB is required for morphotypic multidrug resistance in Mycobacterium avium. Antimicrob. Agents Chemother. 50461-468. [PMC free article] [PubMed]
6. Dubrac, S., I. G. Boneca, O. Poupel, and T. Msadek. 2007. New insights into the WalK/WalR (YycG/YycF) essential signal transduction pathway reveal a major role in controlling cell wall metabolism and biofilm formation in Staphylococcus aureus. J. Bacteriol. 1898257-8269. [PMC free article] [PubMed]
7. Dubrac, S., and T. Msadek. 2004. Identification of genes controlled by the essential YycG/YycF two-component system of Staphylococcus aureus. J. Bacteriol. 1861175-1181. [PMC free article] [PubMed]
8. Dutta, R., and M. Inouye. 2000. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem. Sci. 2524-28. [PubMed]
9. Echenique, J. R., and M. C. Trombe. 2001. Competence repression under oxygen limitation through the two-component MicAB signal-transducing system in Streptococcus pneumoniae and involvement of the PAS domain of MicB. J. Bacteriol. 1834599-4608. [PMC free article] [PubMed]
10. Fabret, C., and J. A. Hoch. 1998. A two-component signal transduction system essential for growth of Bacillus subtilis: implications for anti-infective therapy. J. Bacteriol. 1806375-6383. [PMC free article] [PubMed]
11. Friedman, L., J. D. Alder, and J. A. Silverman. 2006. Genetic changes that correlate with reduced susceptibility to daptomycin in Staphylococcus aureus. Antimicrob. Agents Chemother. 502137-2145. [PMC free article] [PubMed]
12. Fukuchi, K., Y. Kasahara, K. Asai, K. Kobayashi, S. Moriya, and N. Ogasawara. 2000. The essential two-component regulatory system encoded by yycF and yycG modulates expression of the ftsAZ operon in Bacillus subtilis. Microbiology 1461573-1583. [PubMed]
13. Gao, R., T. R. Mack, and A. M. Stock. 2007. Bacterial response regulators: versatile regulatory strategies from common domains. Trends Biochem. Sci. 32225-234. [PMC free article] [PubMed]
14. Gilmour, R., J. E. Foster, Q. Sheng, J. R. McClain, A. Riley, P. M. Sun, W. L. Ng, D. Yan, T. I. Nicas, K. Henry, and M. E. Winkler. 2005. New class of competitive inhibitor of bacterial histidine kinases. J. Bacteriol. 1878196-8200. [PMC free article] [PubMed]
15. Groisman, E. A., and C. Mouslim. 2006. Sensing by bacterial regulatory systems in host and non-host environments. Nat. Rev. Microbiol. 4705-709. [PubMed]
16. Hancock, L., and M. Perego. 2002. Two-component signal transduction in Enterococcus faecalis. J. Bacteriol. 1845819-5825. [PMC free article] [PubMed]
17. Hancock, L. E., and M. Perego. 2004. Systematic inactivation and phenotypic characterization of two-component signal transduction systems of Enterococcus faecalis V583. J. Bacteriol. 1867951-7958. [PMC free article] [PubMed]
18. Hoch, J. A., and T. J. Silhavy (ed.). 1995. Two-component signal transduction. ASM Press, Washington, DC.
19. Hoch, J. A., and K. I. Varughese. 2001. Keeping signals straight in phosphorelay signal transduction. J. Bacteriol. 1834941-4949. [PMC free article] [PubMed]
20. Hoskisson, P. A., and M. I. Hutchings. 2006. MtrAB-LpqB: a conserved three-component system in actinobacteria? Trends Microbiol. 14444-449. [PubMed]
21. Howell, A., S. Dubrac, K. K. Andersen, D. Noone, J. Fert, T. Msadek, and K. Devine. 2003. Genes controlled by the essential YycG/YycF two-component system of Bacillus subtilis revealed through a novel hybrid regulator approach. Mol. Microbiol. 491639-1655. [PubMed]
22. Howell, A., S. Dubrac, D. Noone, K. I. Varughese, and K. Devine. 2006. Interactions between the YycFG and PhoPR two-component systems in Bacillus subtilis: the PhoR kinase phosphorylates the non-cognate YycF response regulator upon phosphate limitation. Mol. Microbiol. 591199-1215. [PubMed]
23. Inouye, M., and R. Dutta (ed.). 2003. Histidine kinases in signal transduction. Academic Press, New York, NY.
24. Kadioglu, A., J. Echenique, S. Manco, M. C. Trombe, and P. W. Andrew. 2003. The MicAB two-component signaling system is involved in virulence of Streptococcus pneumoniae. Infect. Immun. 716676-6679. [PMC free article] [PubMed]
25. Kitayama, T., R. Iwabuchi, S. Minagawa, S. Sawada, R. Okumura, K. Hoshino, J. Cappiello, and R. Utsumi. 2007. Synthesis of a novel inhibitor against MRSA and VRE: preparation from zerumbone ring opening material showing histidine-kinase inhibition. Bioorg. Med. Chem. Lett. 171098-1101. [PubMed]
26. Liu, M., T. S. Hanks, J. Zhang, M. J. McClure, D. W. Siemsen, J. L. Elser, M. T. Quinn, and B. Lei. 2006. Defects in ex vivo and in vivo growth and sensitivity to osmotic stress of group A Streptococcus caused by interruption of response regulator gene vicR. Microbiology 152967-978. [PMC free article] [PubMed]
27. Martin, P. K., T. Li, D. Sun, D. P. Biek, and M. B. Schmid. 1999. Role in cell permeability of an essential two-component system in Staphylococcus aureus. J. Bacteriol. 1813666-3673. [PMC free article] [PubMed]
28. Mascher, T., J. D. Helmann, and G. Unden. 2006. Stimulus perception in bacterial signal-transducing histidine kinases. Microbiol. Mol. Biol. Rev. 70910-938. [PMC free article] [PubMed]
29. Mohedano, M. L., K. Overweg, A. de la Fuente, M. Reuter, S. Altabe, F. Mulholland, D. de Mendoza, P. Lopez, and J. M. Wells. 2005. Evidence that the essential response regulator YycF in Streptococcus pneumoniae modulates expression of fatty acid biosynthesis genes and alters membrane composition. J. Bacteriol. 1872357-2367. [PMC free article] [PubMed]
30. Moker, N., M. Brocker, S. Schaffer, R. Kramer, S. Morbach, and M. Bott. 2004. Deletion of the genes encoding the MtrA-MtrB two-component system of Corynebacterium glutamicum has a strong influence on cell morphology, antibiotics susceptibility and expression of genes involved in osmoprotection. Mol. Microbiol. 54420-438. [PubMed]
31. Ng, W. L., K. M. Kazmierczak, and M. E. Winkler. 2004. Defective cell wall synthesis in Streptococcus pneumoniae R6 depleted for the essential PcsB putative murein hydrolase or the VicR (YycF) response regulator. Mol. Microbiol. 531161-1175. [PubMed]
32. Ng, W. L., G. T. Robertson, K. M. Kazmierczak, J. Zhao, R. Gilmour, and M. E. Winkler. 2003. Constitutive expression of PcsB suppresses the requirement for the essential VicR (YycF) response regulator in Streptococcus pneumoniae R6. Mol. Microbiol. 501647-1663. [PubMed]
33. Ng, W. L., H. C. Tsui, and M. E. Winkler. 2005. Regulation of the pspA virulence factor and essential pcsB murein biosynthetic genes by the phosphorylated VicR (YycF) response regulator in Streptococcus pneumoniae. J. Bacteriol. 1877444-7459. [PMC free article] [PubMed]
34. Ng, W. L., and M. E. Winkler. 2004. Singular structures and operon organizations of essential two-component systems in species of Streptococcus. Microbiology 1503096-3098. [PubMed]
35. Okada, A., Y. Gotoh, T. Watanabe, E. Furuta, K. Yamamoto, and R. Utsumi. 2007. Targeting two-component signal transduction: a novel drug discovery system. Methods Enzymol. 422386-395. [PubMed]
36. Qin, Z., B. Lee, L. Yang, J. Zhang, X. Yang, D. Qu, H. Jiang, and S. Molin. 2007. Antimicrobial activities of YycG histidine kinase inhibitors against Staphylococcus epidermidis biofilms. FEMS Microbiol. Lett. 273149-156. [PubMed]
37. Qin, Z., J. Zhang, B. Xu, L. Chen, Y. Wu, X. Yang, X. Shen, S. Molin, A. Danchin, H. Jiang, and D. Qu. 2006. Structure-based discovery of inhibitors of the YycG histidine kinase: new chemical leads to combat Staphylococcus epidermidis infections. BMC Microbiol. 696. [PMC free article] [PubMed]
38. Saskova, L., L. Novakova, M. Basler, and P. Branny. 2007. Eukaryotic-type serine/threonine protein kinase StkP is a global regulator of gene expression in Streptococcus pneumoniae. J. Bacteriol. 1894168-4179. [PMC free article] [PubMed]
39. Senadheera, M. D., B. Guggenheim, G. A. Spatafora, Y. C. Huang, J. Choi, D. C. 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. 1874064-4076. [PMC free article] [PubMed]
40. Senadheera, M. D., A. W. Lee, D. C. Hung, G. A. Spatafora, S. D. Goodman, and D. G. Cvitkovitch. 2007. The Streptococcus mutans vicX gene product modulates gtfB/C expression, biofilm formation, genetic competence, and oxidative stress tolerance. J. Bacteriol. 1891451-1458. [PMC free article] [PubMed]
41. Shemesh, M., A. Tam, M. Feldman, and D. Steinberg. 2006. Differential expression profiles of Streptococcus mutans ftf, gtf and vicR genes in the presence of dietary carbohydrates at early and late exponential growth phases. Carbohydr. Res. 3412090-2097. [PubMed]
42. Stephenson, K., and J. A. Hoch. 2004. Developing inhibitors to selectively target two-component and phosphorelay signal transduction systems of pathogenic microorganisms. Curr. Med. Chem. 11765-773. [PubMed]
43. Stock, A. M., V. L. Robinson, and P. N. Goudreau. 2000. Two-component signal transduction. Annu. Rev. Biochem. 69183-215. [PubMed]
44. Szurmant, H., T. Fukushima, and J. A. Hoch. 2007. The essential YycFG Two-component system of Bacillus subtilis. Methods Enzymol. 422396-417. [PubMed]
45. Szurmant, H., M. A. Mohan, P. M. Imus, and J. A. Hoch. 2007. YycH and YycI interact to regulate the essential YycFG two-component system in Bacillus subtilis. J. Bacteriol. 1893280-3289. [PMC free article] [PubMed]
46. Szurmant, H., K. Nelson, E. J. Kim, M. Perego, and J. A. Hoch. 2005. YycH regulates the activity of the essential YycFG two-component system in Bacillus subtilis. J. Bacteriol. 1875419-5426. [PMC free article] [PubMed]
47. Szurmant, H., H. Zhao, M. A. Mohan, J. A. Hoch, and K. I. Varughese. 2006. The crystal structure of YycH involved in the regulation of the essential YycFG two-component system in Bacillus subtilis reveals a novel tertiary structure. Protein Sci. 15929-934. [PMC free article] [PubMed]
48. Wagner, C., A. de Saizieu, H.-J. Schönfeld, M. Kamber, R. Lange, C. J. Thompson, and M. G. Page. 2002. Genetic analysis and functional characterization of the Streptococcus pneumoniae vic operon. Infect. Immun. 706121-6128. [PMC free article] [PubMed]
49. Zahrt, T. C., and V. Deretic. 2000. An essential two-component signal transduction system in Mycobacterium tuberculosis. J. Bacteriol. 1823832-3838. [PMC free article] [PubMed]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...