Division of Microbiology
School of Medicine
Loma Linda University
Loma Linda, CA 92350
How do cells sense oxygen and energy?
Bacteria have the remarkable ability to navigate to the precise concentration of oxygen that is optimal for growth. This behavior is called aerotaxis. My laboratory investigates the signal transduction pathways for aerotaxis in E. coli and other bacteria as model systems for learning how oxygen receptors might function in higher organisms. We have recently identified two oxygen transducers, the Aer and Tsr proteins in E. coli. The Aer protein has a PAS domain that is similar to domains in human oxygen-sensing proteins, such as hypoxia-inducible factor-1. Understanding human responses to hypoxia is of considerable medical importance, and our studies of Aer are suggesting common mechanisms for PAS-domain-containing proteins.
Structure-function studies of the aerotaxis transducer Aer and PAS domains.
We have cloned the aer gene. Using cysteine scanning mutagenesis, we have identified residues in Aer that are important for signal transduction, including residues that transform a positive signal into a negative response. Current projects will determine: the structure of Aer and the role of the critical residues; the role of FAD in signaling by Aer; and the cellular components that interact with Aer. A combination of genetic, molecular biology, and biochemical strategies are utilized in answering these questions. This provides students with a broad exposure to current techniques and allows each to extensively pursue a methodology of choice. By forming chimeras with PAS domains of other oxygen sensing proteins we hope to identify common signal transduction strategies for oxygen receptors.
Ecological role of bacterial behavior to oxygen.
Studies in collaboration with Dr. Igor Zhulin and other investigators are aimed at determining how aerotaxis provides a selective advantage to bacteria in their natural environment. Important findings include evidence that the bacteria migrate to a niche where the cellular energy levels are highest for growth. E. coli does not sense oxygen directly. Instead, Aer and Tsr monitor the energy level of the bacteria. By monitoring their own energy, bacteria can avoid not only hypoxic micro-environments but other environments that do not support maximal energy in the bacteria. The concept of energy-sensing has been proposed previously but the Aer signal transduction pathway now provides a mechanism for energy-sensing behavior.
- Garcia D, Watts KJ, Johnson MS and Taylor BL. (2016) Delineating PAS-HAMP interaction surfaces and signalling-associated changes in the aerotaxis receptor Aer. Mol Microbiol 100:156-72.
- Watts KJ, Johnson MS, and Taylor BL. (2011) Different Conformations of the Kinase-on and Kinase-Off Signaling States in the Aer HAMP Domain. J Bacteriol. 193:4095-4103.
- Campbell AJ., Watts KJ, Johnson MS, and Taylor BL. (2011) Role of the F1 region in the Escherichia coli aerotaxis receptor Aer. J Bacteriol. 193:358-66.
- Watts KJ, Taylor BL, Johnson MS. (2011) PAS/poly-HAMP signalling in Aer-2, a soluble haem-based sensor. Mol Microbiol. 79:686-99.
- Campbell AJ, Watts KJ, Johnson MS, Taylor BL. (2010) Gain-of-function mutations cluster in distinct regions associated with the signalling pathway in the PAS domain of the aerotaxis receptor, Aer. Mol Microbiol. 77(3):575-86.
- Watts KJ, Johnson MS, Taylor BL.(2008) Structure-function relationships in the HAMP and proximal signaling domains of the aerotaxis receptor Aer. J Bacteriol. 190(6):2118-27.
- Taylor BL. (2007) Aer on the inside looking out: paradigm for a PAS-HAMP role in sensing oxygen, redox and energy. Mol Microbiol. 65(6):1415-24. Review.
- Amin DN, Taylor BL, Johnson MS. (2007) Organization of the aerotaxis receptor aer in the membrane of Escherichia coli. J Bacteriol. 189(20):7206-12.
- Taylor BL, Watts KJ, Johnson MS. (2007) Oxygen and redox sensing by two-component systems that regulate behavioral responses: behavioral assays and structural studies of aer using in vivo disulfide cross-linking. Methods Enzymol. 422:190-232.
- Edwards JC, Johnson MS, Taylor BL. (2006) Differentiation between electron transport sensing and proton motive force sensing by the Aer and Tsr receptors for aerotaxis. Mol Microbiol. 62(3):823-37.
- Watts KJ, Sommer K, Fry SL, Johnson MS, Taylor BL. (2006) Function of the N-terminal cap of the PAS domain in signaling by the aerotaxis receptor Aer. J Bacteriol. 188(6):2154-62.
- Watts KJ, Johnson MS, Taylor BL. (2006) Minimal requirements for oxygen sensing by the aerotaxis receptor Aer. Mol Microbiol. 59(4):1317-26.
- Amin DN, Taylor BL, Johnson MS. (2006) Topology and boundaries of the aerotaxis receptor Aer in the membrane of Escherichia coli. J Bacteriol. 188(3):894-901.
- Ma Q, Johnson MS, Taylor BL. (2005) Genetic analysis of the HAMP domain of the Aer aerotaxis sensor localizes flavin adenine dinucleotide-binding determinants to the AS-2 helix. J Bacteriol. 187(1):193-201.
- Ma Q, Roy F, Herrmann S, Taylor BL, Johnson MS. (2004) The Aer protein of Escherichia coli forms a homodimer independent of the signaling domain and flavin adenine dinucleotide binding. J Bacteriol. 186(21):7456-9.
- Watts KJ, Ma Q, Johnson MS, Taylor BL. (2004) Interactions between the PAS and HAMP domains of the Escherichia coli aerotaxis receptor Aer. J Bacteriol. 86(21):7440-9.
- Herrmann S, Ma Q, Johnson MS, Repik AV, Taylor BL. (2004) PAS domain of the Aer redox sensor requires C-terminal residues for native-fold formation and flavin adenine dinucleotide binding. J Bacteriol. 186(20):6782-91
- Taylor BL. (2004) An alternative strategy for adaptation in bacterial behavior.J Bacteriol. 186(12):3671-3.
- Greer-Phillips SE, Alexandre G, Taylor BL, Zhulin IB. (2003) Aer and Tsr guide Escherichia coli in spatial gradients of oxidizable substrates. Microbiology. 149(Pt 9):2661-7.
- Yu HS, Saw JH, Hou S, Larsen RW, Watts KJ, Johnson MS, Zimmer MA, Ordal GW, Taylor BL, Alam M. (2002) Aerotactic responses in bacteria to photoreleased oxygen. FEMS Microbiol Lett. 217(2):237-42.
- Taylor BL, Rebbapragada A, Johnson MS. (2001) The FAD-PAS domain as a sensor for behavioral responses in Escherichia coli. Antioxid Redox Signal. 3(5):867-79. Review.