Premium
Defining the Mga regulon: comparative transcriptome analysis reveals both direct and indirect regulation by Mga in the group A streptococcus
Author(s) -
Ribardo Deborah A.,
McIver Kevin S.
Publication year - 2006
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2006.05381.x
Subject(s) - regulon , biology , transcriptome , gene , virulence , genetics , operon , microbiology and biotechnology , mutant , gene expression
Summary The regulator Mga in the group A streptococcus (GAS) is known to directly activate several virulence genes important for colonization and immune evasion. Transcriptome analysis comparing two mga‐1 serotypes (M1 SF370, M6 JRS4) and one mga‐2 serotype (M4 GA40634) against their isogenic mga ‐inactivated strains uncovered a broader Mga regulon profile containing both activated and repressed genes with predicted functions primarily related to sugar metabolism. This was reflected in the altered abilities of M1 and M4 Mga mutants to grow in chemically defined media with a single sugar source compared with their wild‐type counterparts. Although the M1 and M4 Mga profiles were similar, the M6 JRS4 was clearly distinct, even from other M6 strains. Real‐time RT‐PCR and Northern blots confirmed that established core Mga regulon genes directly activated by Mga ( emm , scpA , sof , fba ) exhibited the highest activation levels across all strains tested. Spy2036 encoding a cytosolic hypothetical protein was highly activated in all three serotypes and was called g ene r egulated by M ga ( grm ). Mga bound directly to P grm , which overlaps the Mga‐regulated P sof in OF + strains, suggesting that grm is part of the core Mga regulon and Mga is able to activate divergently transcribed genes from a single site. Furthermore, Mga activated speB when detectable in the wild‐type strain, although direct binding of Mga to P speB could not be demonstrated. Thus, Mga is able to both directly and indirectly regulate genes shown to be important for virulence and the metabolic homeostasis of GAS.