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Journal of Bacteriology, May 2008, p. 3095-3097, Vol. 190, No. 9
0021-9193/08/$08.00+0     doi:10.1128/JB.00253-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

GUEST COMMENTARY

A Sense of Self-Worth: Energy Taxis Provides Insight into How Helicobacter pylori Navigates through Its Environment

Gladys Alexandre^*

Department of Biochemistry, Cellular and Molecular Biology and Department of Microbiology, The University of Tennessee, Knoxville, Tennessee

The ability to perceive and respond appropriately to environmental cues is an essential prerequisite to the survival and adaptation of microorganisms to changes in their surroundings. One of the best-understood responses involves the chemotaxis two-component signal transduction system in Escherichia coli, which functions to relay sensory information about the surroundings to the flagellar motility apparatus (11, 23). Although the protein components of the E. coli chemotaxis signal transduction pathway have been characterized in molecular detail, the exact role that chemotaxis plays in the ecology of the organism remains poorly understood. A priori, the ability to sense and navigate toward a particular ecological habitat provides motile microorganisms with a competitive advantage; chemotaxis has been suggested, and often demonstrated experimentally, to be important in host recognition by various pathogenic and beneficial microorganisms (2, 9, 13, 27). An article in this issue by Schweinitzer et al. (18) provides new insight into how the gastric pathogen Helicobacter pylori monitors changes in its environment, suggesting a mechanism through which bacterial chemotaxis may direct and maintain H. pylori within a narrow zone deep in the gastric mucus, leading to persistent colonization and infection.

Chemotaxis and niche adaptation.

Motile bacteria are capable of navigating in gradients of oxygen, light, ions, and nutrients by constantly monitoring their environment for change in order to occupy a position that is optimal for survival and growth. The ability to modulate (increasing or decreasing) the probability of random changes in swimming direction allows motile bacteria to navigate in chemical gradients, resulting in chemotaxis (3, 23).

In chemotaxis, sensory input to the flagellar apparatus is provided by a set of membrane-bound chemoreceptors. Chemoreceptors are comprised of two functional domains, namely, an N-terminal sensory domain and a conserved C-terminal signaling domain that interacts with the cytoplasmic signal transduction machinery (11, 23). The N-terminal sensing domains of chemoreceptors can be located in either the periplasm or the cytoplasm and are generally not conserved. Variations in the sensory specificity of the N-terminal domains of chemoreceptors reflect the diverse cues that a motile microorganism can detect and to which it may respond (25). Environmental cues may be detected either directly, by binding of a ligand to the sensory domains of chemoreceptors (metabolism-independent chemotaxis), or indirectly, by causing a change in the intracellular energy level that itself is detected by a redox-sensitive cofactor within the sensory domain of the chemoreceptor or by a proton motive force (PMF)-sensitive domain. Metabolism-dependent behavior is known as energy taxis, in which the signal for a behavioral response originates within the electron transport system, where a change in the rate of electron transport (or a related parameter) is detected by a signal transduction system (19). Effectors for energy taxis affect the bacterial redox potential and PMF and include compounds such as terminal electron acceptors, redox chemicals (including inhibitors of the electron transport system), and metabolizable substrates (donors of reducing equivalents to the electron transport system). Experimental evidence for the ability of cells to monitor intracellular energy levels has been obtained with E. coli, which possesses two membrane-bound chemoreceptors, Aer and Tsr, that sense different parameters related to intracellular energy levels (redox potential for Aer and probably the PMF for Tsr) and signal to the flagellar motors via the chemotaxis signal transduction pathway (8, 16), thus functioning in energy taxis.

The human gastric pathogen Helicobacter pylori utilizes a set of five sheathed polar flagella that provide optimum motility in the viscous environment of the gastric mucosa (6). Flagellar motility is a virulence factor in that nonmotile or nonflagellated mutants are attenuated in colonization of the stomach in animal models (7, 14). Although chemotaxis has been described for H. pylori in vitro and in vivo (2, 4, 5, 9, 26), the importance of this behavior in the ability of this pathogen to locate its niche within the stomach mucus was recognized only recently (17, 24). Schreiber et al. (17) used a microdissection method that allowed them to establish that H. pylori colonizes and persists in the stomach in a very narrow zone close to the gastric epithelial surface and away from the lumen, where the acidic pH would inhibit growth and motility These findings suggested that H. pylori cells were capable of actively orienting in this environment so that they could reside within this narrow zone despite active mucus turnover. Furthermore, sensing and navigating along the pH gradient in the mucus were found to be key determinants in the establishment and persistence of H. pylori in its preferred niche (17). Considering the effect that environmental pH has on the proton gradient component of the PMF, two mechanisms were invoked for pH taxis, including direct sensing of the proton gradient and sensing of the effect that a decrease in the proton gradient across the bacterial membrane has on intracellular energy levels. A dedicated chemoreceptor(s) was also suggested to be a sensor for pH taxis in H. pylori (17), which is consistent with the previous observation that two of the E. coli chemoreceptors (Tsr and Tar) could mediate pH taxis in gradients of permeant weak acids (Tsr) and bases (Tar) (22). The genome of H. pylori encodes four putative chemoreceptors, three of which are membrane bound (TlpA, TlpB, and TlpC) and one of which is cytoplasmic (TlpD) (1, 21). The N-terminal sensory domains of the H. pylori chemoreceptors do not have detectable sequence similarity to any sensory domains of known function, and the exact sensory specificities of these chemoreceptors have remained unknown, until recently. One of the H. pylori chemoreceptors, TlpB, was recently found to be essential for temporal pH sensing in this species (5). Notably, TlpB mediated a repellent response (negative chemotaxis), which allows cells to escape environments where the pH is too low to support growth or motility. However, such a tactic response may not be sufficient to ensure that cells persist in dynamic environments, where other gradients (that may result from active local metabolism) or limiting factors for growth may be present.

Navigating along "energy" gradients.

Energy taxis was put forward as an additional or alternative hypothesis to explain the movement of H. pylori in pH gradients. Schweinitzer et al. (18) found that the swimming motility bias of H. pylori wild-type cells was affected by growth conditions that impacted energy yields. In order to accurately describe a taxis mechanism, sensitive behavioral assays must be used to quantitatively measure tactic responses. This is not a trivial issue, since very often chemotaxis assays that work well in the model organism E. coli do not provide insightful information for microorganisms that have a different type of motile behavior. Schweinitzer et al. (18) used a set of sensitive spatial and temporal assays to obtain convincing evidence for energy sensing in H. pylori by demonstrating that two electron transport inhibitors that reduce the intracellular energy levels can trigger a concentration-dependent change in the swimming motility bias. Restoring the electron flow through the respiratory chain (and thus increasing energy production) by using artificial electron donors also restored the swimming motility bias. The demonstration that H. pylori is capable of energy sensing is significant because it suggests that by coupling sensing of the intracellular energy to motility, swimming H. pylori cells may navigate toward niches that support optimal energy generation, thus integrating sensory information about all nutrient and pH gradients into a single response.

In addition to characterizing energy taxis in H. pylori, Schweinitzer et al. (18) have attributed most of the energy-sensing capabilities to a single putative chemoreceptor, TlpD. They used the set of behavioral assays described above, a defined tlpD mutant, and a triple tlpABC mutant to determine that TlpD is the major chemoreceptor responsible for sensing perturbation of the electron transport system (energy sensing) and initiating a repellent response. However, the mechanism(s) by which this proposed chemoreceptor might sense an energy-related parameter remains to be determined. TlpD is a cytoplasmic chemoreceptor-like protein that possesses a short N-terminal sensory domain that does not have any apparent homolog that could be indicative of a sensing mechanism. Furthermore, unusual features of TlpD are intriguing and, if confirmed, may provide significant insight into the mechanism(s) related to the energy-sensing functions of TlpD. First, under conditions of overexpression from a plasmid, TlpD localizes to the cytoplasmic face of the membrane, but no distinct preferential localization can be identified. This is highly unexpected, since in E. coli as well as other species studied so far in this respect, chemoreceptors are clustered, typically at the cell poles, and this organization is essential to chemotaxis in E. coli (10-12). It is noteworthy that the H. pylori chemotaxis signal transduction pathway is significantly divergent from that of E. coli in that it includes chemotaxis proteins that are not present in E. coli (9, 15, 20) and could account for this unusual (although preliminary) observation. Second, TlpD mediated a stronger response under conditions where cells generated relatively lower energy, suggesting that sensing via TlpD is dominant under these specific conditions. This effect could be correlated with a change in the expression of TlpD itself, a potential energy-transducing interacting partner(s), or even some of the other chemoreceptors or chemotaxis proteins. To date, two (TlpB and TlpD) of four chemoreceptors have been found to monitor energy-related parameters in H. pylori, underscoring the likely advantage that this behavior provides to the organism with restricted metabolic capabilities. How the cues sensed by TlpD and TlpB are integrated into a response and how each cue can modulate adaptation to the gastric mucosa remain to be understood. The work by Schweinitzer et al. (18) paves the way for the design of experiments that could directly address the contributions of these behaviors to niche adaptation.

ACKNOWLEDGMENTS

I thank Calvin Green, Amber Bible, Zhihong Xie, Beth Mullin, and Christine Josenhans for useful comments on the manuscript.

Research in my laboratory on chemosensory transduction in plant-associated bacteria is supported by an NSF career award (MCB-0622277).

 
* Mailing address: Department of Biochemistry, Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN 37996. Phone: (865) 974-0866. Fax: (865) 974-6306. E-mail: galexan2{at}utk.edu

FOOTNOTES

Published ahead of print on 29 February 2008.

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

REFERENCES

1
1. Alm, R. A., L.-S. L. Ling, D. T. Moir, B. L. King, E. D. Brown, P. C. Doig, D. R. Smith, B. Noonan, B. C. Guild, B. L. deJonge, G. Carmel, P. J. Tummino, A. Caruso, M. Uria-Nickelsen, D. M. Mills, C. Ives, R. Gibson, D. Merberg, S. D. Mills, Q. Jiang, D. E. Taylor, G. F. Vovis, and T. J. Trust. 1999. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397:176-180.[CrossRef][Medline]
2
2. Andermann, T. M., Y.-T. Chen, and K. M. Ottemann. 2002. Two predicted chemoreceptors of Helicobacter pylori promote stomach infection. Infect. Immun. 70:5877-5881.[Abstract/Free Full Text]
3
3. Berg, H. C., and D. A. Brown. 1972. Chemotaxis in Escherichia coli analyzed by three-dimensional tracking. Nature 239:500-504.[CrossRef][Medline]
4
4. Cerda, O., A. Rivas, and H. Toledo. 2003. Helicobacter pylori strain ATCC700392 encodes a methyl-accepting chemotaxis receptor protein (MCP) for arginine and sodium bicarbonate. FEMS Microbiol. Lett. 224:175-181.[CrossRef][Medline]
5
5. Croxen, M. A., G. Sisson, R. Melano, and P. S. Hoffman. 2006. The Helicobacter pylori chemotaxis receptor TlpB (HP0103) is required for pH taxis and for the colonization of the gastric mucosa. J. Bacteriol. 188:2656-2665.[Abstract/Free Full Text]
6
6. Eaton, K. A., D. R. Morgan, and S. Krakowka. 1992. Motility as a factor in the colonisation of gnotobiotic piglets by Helicobacter pylori. J. Med. Microbiol. 37:123-127.[Abstract/Free Full Text]
7
7. Eaton, K. A., S. Suerbaum, C. Josenhans, and S. Krakowka. 1996. Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. Infect. Immun. 62:3289-3298.
8
8. Edwards, J. C., M. S. Johnson, and B. L. Taylor. 2006. Differentiation between electron transport sensing and proton motive force sensing by the Aer and Tsr receptors for aerotaxis. Mol. Microbiol. 62:823-837.[CrossRef][Medline]
9
9. Foynes, S., N. Dorrell, S. J. Ward, R. A. Stabler, A. A. McColm, A. N. Rycroft, and B. N. Wren. 2000. Helicobacter pylori possesses two CheY response regulators and a histidine kinase sensor, CheA, which are essential for chemotaxis and colonization of the gastric mucosa. Infect. Immun. 68:2016-2023.[Abstract/Free Full Text]
10
10. Gestwicki, J. E., A. C. Lamanna, R. M. Harshey, L. L. McCarter, L. L. Kiessling, and J. Adler. 2000. Evolutionary conservation of methyl-accepting chemotaxis protein location in Bacteria and Archaea. J. Bacteriol. 182:6499-6502.[Abstract/Free Full Text]
11
11. Hazelbauer, G. L., J. J. Falke, and J. S. Parkinson. 2008. Bacterial chemoreceptors: high-performance signaling in networked arrays. Trends Biochem. Sci. 33:9-19.[CrossRef][Medline]
12
12. Maddock, J. R., and L. Shapiro. 1993. Polar location of the chemoreceptor complex in the Escherichia coli cell. Science 259:1717-1723.[Abstract/Free Full Text]
13
13. Miller, L. D., C. K. Yost, M. F. Hynes, and G. Alexandre. 2007. The major chemotaxis gene cluster of Rhizobium leguminosarum bv. viciae is essential for competitive nodulation. Mol. Microbiol. 63:348-362.[CrossRef][Medline]
14
14. Otteman, K. M., and A. Lowenthal. 2002. Helicobacter pylori uses motility for both initial colonization and to attain robust infection. Infect. Immun. 70:1984-1990.[Abstract/Free Full Text]
15
15. Pittman, M. S., M. Goodwin, and D. J. Kelly. 2001. Chemotaxis in the human gastric pathogen Helicobacter pylori: different roles for CheW and the three CheV paralogues, and evidence for CheV2 phosphorylation. Microbiology 147:2493-2504.[Abstract/Free Full Text]
16
16. Rebbapragada, A., M. S. Johnson, G. P. Harding, A. J. Zuccarelli, H. M. Fletcher, I. B. Zhulin, and B. L. Taylor. 1997. The Aer protein and the serine chemoreceptor Tsr independently sense intracellular energy levels and transduce oxygen, redox, and energy signals for Escherichia coli behavior. Proc. Natl. Acad. Sci. USA 94:10541-10546.[Abstract/Free Full Text]
17
17. Schreiber, S., M. Konradt, C. Groll, P. Scheid, G. Hanauer, H.-O. Werling, C. Josenhans, and S. Suerbaum. 2004. The spatial orientation of Helicobacter pylori in the gastric mucus. Proc. Natl. Acad. Sci. USA 101:5024-5029.[Abstract/Free Full Text]
18
18. Schweinitzer, T., T. Mizote, N. Ishikawa, A. Dudnik, S. Inatsu, S. Schreiber, S. Suerbaum, S.-I. Aizawa, and C. Josenhans. 2008. Functional characterization and mutagenesis of the proposed behavioral sensor TlpD of Helicobacter pylori. J. Bacteriol. 190:3244.[Abstract/Free Full Text]
19
19. Taylor, B. L., I. B. Zhulin, and M. S. Johnson. 1999. Aerotaxis and other energy-sensing behavior in bacteria. Annu. Rev. Microbiol. 53:103-128.[CrossRef][Medline]
20
20. Terry, K., A. C. Go, and K. M. Ottemann. 2006. Proteomic mapping of a suppressor of non-chemotactic cheW mutants reveals that Helicobacter pylori contains a new chemotaxis protein. Mol. Microbiol. 61:871-882.[CrossRef][Medline]
21
21. Tomb, J. F., O. White, A. R. Kerlavage, R. A. Clayton, G. G. Sutton, R. D. Fleischmann, K. A. Ketchum, H. P. Klenk, S. Gill, B. A. Dougherty, K. Nelson, J. Quackenbush, L. Zhou, E. F. Kirkness, S. Peterson, B. Loftus, D. Richardson, R. Dodson, H. G. Khalak, A. Glodek, K. McKenney, L. M. Fitzegerald, N. Lee, M. D. Adams, E. K. Hickey, D. E. Berg, J. D. Gocayne, T. R. Utterback, J. D. Peterson, J. M. Kelley, M. D. Cotton, J. M. Weidman, C. Fujii, C. Bowman, L. Watthey, E. Wallin, W. S. Hayes, M. Borodovsky, P. D. Karp, H. O. Smith, C. M. Fraser, and J. C. Venter. 1997. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388:539-547.[CrossRef][Medline]
22
22. Umemura, T., Y. Matsumoto, K. Ohnishi, M. Homma, and I. Kawagishi. 2002. Sensing of cytoplasmic pH by bacterial chemoreceptors involves the linker region that connects the membrane-spanning and the signal-modulating helices. J. Biol. Chem. 277:1593-1598.[Abstract/Free Full Text]
23
23. Wadhams, G. H., and J. P. Armitage. 2004. Making sense of it all: bacterial chemotaxis. Nat. Rev. Mol. Cell Biol. 5:1024-1037.[CrossRef][Medline]
24
24. Williams, S. M., Y.-T. Chen, T. M. Andermann, E. E. Carter, D. J. McGee, and K. M. Ottemann. 2007. Helicobacter pylori chemotaxis modulates inflammation and bacterium-gastric epithelium interactions in infected mice. Infect. Immun. 75:3747-3757.[Abstract/Free Full Text]
25
25. Worku, M. L., Q. N. Karim, J. Spencer, and R. L. Sidebotham. 2004. Chemotactic response of Helicobacter pylori to human plasma and bile. J. Med. Microbiol. 53:807-811.[Abstract/Free Full Text]
26
26. Wuichet, K., R. P. Alexander, and I. B. Zhulin. 2007. Comparative genomic and protein sequence analyses of a complex system controlling bacterial chemotaxis. Methods Enzymol. 422:3-31.
27
27. Yao, J., and C. Allen. 2006. Chemotaxis is required for virulence and competitive fitness in the bacterial wilt pathogen Ralstonia solanacearum. J. Bacteriol. 188:3697-3708.[Abstract/Free Full Text]

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Journal of Bacteriology, May 2008, p. 3095-3097, Vol. 190, No. 9
0021-9193/08/$08.00+0     doi:10.1128/JB.00253-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Alexandre, G. Search for Related Content PubMed PubMed Citation Articles by Alexandre, G.