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The arginine deiminase system (ADS) of<jats:italic>S. gordonii<\/jats:italic>enables cells to produce, ornithine, ammonia, CO<jats:sub>2<\/jats:sub>, and ATP from arginine hydrolysis, augmenting the acid tolerance of the organism. The ADS genes are substrate inducible and sensitive to catabolite repression, mediated through ArcR and CcpA, respectively, but the system also requires low pH and anaerobic conditions for optimal activation. Here, we demonstrate that the CiaRH and ComDE two-component systems (TCS) are required for low-pH-dependent expression of ADS genes in<jats:italic>S. gordonii<\/jats:italic>. Further, the VicRK TCS is required for optimal ADS gene expression under anaerobic conditions and enhances the sensitivity of the operon to repression by oxygen. The known anaerobic activator of the ADS, Fnr-like protein (Flp), appeared to act independently of the Vic TCS. Mutants of<jats:italic>S. gordonii<\/jats:italic>lacking components of the CiaRH, ComDE, or VicRK grew more slowly in acidified media and were more sensitive to killing at lethal pH values and to agents that induce oxidative stress. This study provides the first evidence that TCS can regulate the ADS of bacteria in response to specific environmental signals and reveals some notable differences in the contribution of CiaRH, ComDE, and VicRK to viability and stress tolerance between the oral commensal<jats:italic>S. gordonii<\/jats:italic>and the oral pathogen<jats:italic>Streptococcus mutans<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/jb.01053-09","type":"journal-article","created":{"date-parts":[[2009,9,26]],"date-time":"2009-09-26T01:10:52Z","timestamp":1253927452000},"page":"7353-7362","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Multiple Two-Component Systems Modulate Alkali Generation in<i>Streptococcus gordonii<\/i>in Response to Environmental Stresses"],"prefix":"10.1128","volume":"191","author":[{"given":"Yaling","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oral Biology, University of Florida, Gainesville, Florida 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Burne","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, University of Florida, Gainesville, Florida 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01410-07"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00546-07"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00536-06"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.3.1631-1642.2006"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0021-9258(17)41681-4","volume":"156","year":"1944","unstructured":"Archibald, R. 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