Comparative functional analysis of the lac operons in Streptococcus pyogenes

Abstract

SummaryHaving no known environmental reservoir, Streptococcus pyogenes, a bacterium responsible for a wider variety of human diseases than any other bacterial species, must rely on its host for metabolic substrates. Although a streptococcal aldolase, LacD.1, has been adapted to virulence gene regulation, both LacD.1 and a paralogous protein, LacD.2, are predicted to function in the tagatose 6-phosphate pathway for lactose and galactose utilization. In order to gain insight into the mechanism of the LacD.1 regulatory pathway and the role of genome context in the emergence of LacD.1's novel regulatory functions, we compared the function and regulation of the Lac.1 and Lac.2 loci. The Lac.1 operon is not inducible, and regulation by LacD.1 is independent of a functional tagatose 6-phosphate pathway and enhanced by the conserved truncation of upstream Lac.1 genes. In contrast, Lac.2 expression is sensitive to environmental carbohydrates, and LacD.2, not LacD.1, contributes to growth on galactose. Thus, we conclude that the Lac.1 locus has been specialized to participate in regulation, leaving efficient utilization of carbohydrate sources to the Lac.2 locus. The adaptation of LacD for transcription regulation may be an underappreciated strategy among prokaryotes, as homologues of this multifaceted enzyme are present in a broad range of species.

Streptococcus pyogenes Ser/Thr Kinase-regulated Cell Wall Hydrolase Is a Cell Division Plane-recognizing and Chain-forming Virulence Factor

“…In the present study, the most notable differentially down-regulated carbohydrate genes (2-4-fold) in both M1⌬CdhA and M1CdhA⌬C55 were the malM operon, lacA.1, lacA.2, lacB.1, lacD.2, and lacE. The down-regulation of these genes in GAS has recently been reported to inversely affect GAS virulence (62)(63)(64)(65)(66). Thus, the attenuation of virulence in mutants as a result of a complete or partial deletion of the cdhA genes can also be attributed to the down-regulation of carbohydrate metabolism genes.…”

Effects of the ERES Pathogenicity Region Regulator Ralp3 on Streptococcus pyogenes Serotype M49 Virulence Factor Expression

“…The lac2 operon is involved in carbohydrate metabolism and encodes genes required in the tagatose-6-phosphate pathway (33). However, the lac1 operon seems to be involved in virulence gene regulation (25). Furthermore, Mga influences directly or indirectly over 10% of the GAS transcriptome, including genes encoded for sugar utilization, e.g., the fru operon (31).…”

“…GAS, as one of the major pathogenic lactic acid bacteria, utilizes glucose as a main carbon source (40). GAS glycolysis has recently been studied by a systems biology approach, and the first GAS glycolytic kinetic model has been published (23).Different transcriptomic studies have shown that virulence regulation by GAS is linked to genes that are important for sugar utilization (24,25,36,38). In particular, starch-degrading and carbohydrate-metabolism genes are differentially regulated during GAS stationary-phase survival in saliva (37).…”

“…Different transcriptomic studies have shown that virulence regulation by GAS is linked to genes that are important for sugar utilization (24,25,36,38). In particular, starch-degrading and carbohydrate-metabolism genes are differentially regulated during GAS stationary-phase survival in saliva (37).…”

A decade of molecular pathogenomic analysis of group A Streptococcus

“…Simi- larly, a genome-wide investigation of SpeB regulation led to the discovery that a lactose catabolism enzyme (LacD.1) has evolved to coordinate alterations in GAS virulence factor production as a result of changes in carbon source availability ( Figure 1) (79). Analysis of completed GAS genomes led to the discovery that one of the two GAS lactose operons has retained a catabolic role, whereas the other has evolved a regulatory function ( Figure 1) (80). In addition to discovering ties between central metabolic processes and pathogenesis, GAS genome-wide studies have also revealed interactions between metal regulation, oxidative stress, and pathogenesis.…”