- ASSISTANT PROFESSOR Ophthalmology
Physiological and regulatory implications of the housekeeping functions of Bacillus subtilis tetL gene
TetL is a multifunctional antiporter in Bacillus subtilis that can use a tetracycline (Tc)-divalent metal complex (with a single positive charge) or Na+ as an efflux substrate in exchange for a greater number of H+. The antiporter has physiological roles in Na+- and alkali-resistance, as well as in Tc-resistance. A mutant of B. subtilis that had a transposon insertion in the chromosomal tetL gene was Na+- and alkali-sensitive. This led to the demonstration of multiple antiport functions for TetL that are not related to its role in antibiotic-resistance. Deletion of tetL results in a spectrum of pleiotropic effects, such as Na+-, Co2+- and alkali-sensitivity as well as Tc-sensitivity. Microarray analysis of transcriptomes of such deletion strains further confirmed the irreversibility of several phenotypic features of the tetL mutants. We hypothesized that secondary mutations arise subsequent to tetL deletion that may be adaptive to stresses caused by loss of tetL. We are attempting to determine which of these secondary mutations in a tetL deletion strain might account for phenotypes such as Co2+ sensitivity. We are also trying to elucidate any possible transcriptional components around the tetL locus that might account for the Na+- and alkali-sensitive phenotype of the original mutant.\r\n
Collaborating with Dr. Bechhofer??s Lab on the tetL project\r\n
Wei Y, Guffanti AA, Ito M, Krulwich TA. Bacillus subtilis YqkI is a novel malic/Na+ lactate antiporter that enhances growth on malate at low protonmotive force. J Biol Chem. 2000 Sep 29; 275(39): 30287-30292.
Wang W, Guffanti AA, Wei Y, Ito M, Krulwich TA. Two types of Bacillus subtilis tetA(L) deletion strains reveal the physiological importance of TetA(L) in K+ acquisition as well as in Na+, alkali, and tetracycline resistance. J Bacteriol. 2000 Apr; 182(8): 2088-2095.
Wei Y, Hu MH. The study of P68 RNA helicase on cell transformation. Yi Chuan Xue Bao. 2001 Nov; 28(11): 991-996.
Wei Y, Bechhofer DH. Tetracycline induces stabilization of mRNA in Bacillus subtilis. J Bacteriol. 2002 Feb; 184(4): 889-894.
Guffanti AA, Wei Y, Rood SV, Krulwich TA. An antiport mechanism for a member of the cation diffusion facilitator family: divalent cations efflux in exchange for K+ and H+ . Mol Microbiol. 2002 Jul; 45(1): 145-153.
Hicks DB, Wang Z, Wei Y, Kent R, Guffanti AA, Banciu H, Bechhofer DH, Krulwich TA. A tenth atp gene and the conserved atpI gene of a Bacillus atp operon have a role in Mg2+ uptake. Proc Natl Acad Sci U S A. 2003 Sep 2; 100(18): 10213-10218.
Wei Y, Southworth TW, Kloster H, Ito M, Guffanti AA, Moir A, Krulwich TA. Mutational loss of a K+ and NH4+ transporter affects the growth and endospore formation of alkaliphilic Bacillus pseudofirmus OF4. J Bacteriol. 2003 Sep; 185(17): 5133-5147.
Ito M, Xu H, Guffanti AA, Wei Y, Zvi L, Clapham DE, Krulwich TA. The voltage-gated Na+ channel NaVBP has a role in motility, chemotaxis, and pH homeostasis of an alkaliphilic Bacillus. Proc Natl Acad Sci U S A. 2004 Jul 20; 101(29): 10566-10571.
Liu J, Xue Y, Wang Q, Wei Y, Swartz TH, Hicks DB, Ito M, Ma Y, Krulwich TA. The activity profile of the NhaD-type Na+(Li+)/H+ antiporter from the soda Lake Haloalkaliphile Alkalimonas amylolytica is adaptive for the extreme environment. J Bacteriol 2005 Nov; 187(22): 7589-7595.
Wei Y, Deikus G, Powers B, Shelden V, Krulwich TA, Bechhofer DH. Adaptive gene expression in Bacillus subtilis strains deleted for tetL. J Bacteriol 2006 Oct; 188(20): 7090-100.
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