Regulation and Physiologic Significance of the Agmatine Deiminase System of Streptococcus mutans UA159

Abstract

We previously demonstrated that Streptococcus mutans expresses a functional agmatine deiminase system (AgDS) encoded by the agmatine-inducible aguBDAC operon (A. R. Griswold, Y. Y. Chen, and R. A. Burne, J. Bacteriol. 186:1902Bacteriol. 186: -1904Bacteriol. 186: , 2004). The AgDS yields ammonia, CO 2 , and ATP while converting agmatine to putrescine and is proposed to augment the acid resistance properties and pathogenic potential of S. mutans. To initiate a study of agu gene regulation, the aguB transcription initiation site was identified by primer extension and a putative 70 -like promoter was mapped 5 to aguB. Analysis of the genome database revealed an open reading frame (SMU.261c) encoding a putative transcriptional regulator located 239 bases upstream of aguB. Inactivation of SMU.261c decreased AgD activity by sevenfold and eliminated agmatine induction. AgD was also found to be induced by certain environmental stresses, including low pH and heat, implying that the AgDS may also be a part of a general stress response pathway of this organism. Interestingly, an AgDS-deficient strain was unable to grow in the presence of 20 mM agmatine, suggesting that the AgDS converts a growth-inhibitory substance into products that can enhance acid tolerance and contribute to the competitive fitness of the organism at low pH. The capacity to detoxify and catabolize agmatine is likely to have major ramifications on oral biofilm ecology.

Agmatine deiminase pathway genes in Lactobacillus brevis are linked to the tyrosine decarboxylation operon in a putative acid resistance locus

“…faecalis. In particular, they contain two genes of putative AgDIs instead of one and have a gene encoding a putative transcription regulator that belongs to the RpiR family rather than the LysR family (Griswold et al, 2006) and that is positioned differently in the cluster. In line with these differences, the translated proteins of Lb.…”

“…faecalis and Lc. lactis contain clusters with a single AgDI gene and the gene of a transcriptional regulator of the LysR family located upstream and transcribed separately (Griswold et al, 2006). The clusters in Lb.…”

“…The specificity of the latter was not examined, but was proposed to be the agmatine/putrescine exchanger. Transcription of the operon is under the control of the AguR regulator, which is encoded by the aguR gene located upstream of the operon (Griswold et al, 2006). Clusters of similar genes were found in the genomes of strains of Lactococcus lactis, Listeria monocytogenes, Lactobacillus sakei and Pediococcus pentosaceus (see Fig.…”

“…In bacteria, biogenic amines may serve physiological functions such as cell proliferation control, but they are more generally released into the medium as the end products of the catabolic pathways (Tabor & Tabor, 1985;Griswold et al, 2006). In fact, excretion of the amine is an essential step in the pathways (see below).…”

Global transcriptional analysis of acid-inducible genes in Streptococcus mutans: multiple two-component systems involved in acid adaptation

“…The aciduricity of this organism has been attributed largely to the proton-extruding F 1 F 0 -ATPase that functions well at pH 5.0 and below, allowing the organism to maintain adequate DpH when the external pH falls to 4.0 and lower (Bender et al, 1986;Cotter & Hill, 2003). Other mechanisms of acid resistance in S. mutans include induction of stress proteins (Hamilton & Svensäter, 1998;Len et al, 2004;Svensäter et al, 1997;Wilkins et al, 2002), changes in membrane-associated proteins and fatty acid composition (Fozo et al, 2007;Hasona et al, 2007), DNA repair enzymes (Hahn et al, 1999;Hanna et al, 2001) and increase in alkali production through several metabolic pathways (Burne et al, 1999;Griswold et al, 2006). Moreover, the ComCDE quorum-sensing system has been found to play a role in cell-density-dependent acid tolerance by S. mutans (Li et al, 2001b).…”