CodY, a master integrator of metabolism and virulence in Gram-positive bacteria

Brinsmade, Shaun R.

doi:10.1007/s00294-016-0656-5

Cited by 72 publications

(56 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…notype for the codY-null mutants has also been reported for B. subtilis, Bacillus thuringiensis, and C. difficile (22)(23)(24)33). Interestingly, while disruption of the codY gene increased the level of sporulation in two strains of C. difficile, significant differences in the sporulation frequencies of those two codY-null mutants were noted; i.e., a codY-null mutant of a poorly sporulating strain exhibited a 2-fold increase in sporulation compared to that for its wild-type parent, while a codY-null mutant of a strongly sporulating strain exhibited 1,400-fold more sporulation than its wild-type parent (23).…”

Section: Figmentioning

confidence: 58%

CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101

Freedman

Evans

et al. 2017

Infect Immun

View full text Add to dashboard Cite

Clostridium perfringens type D strains cause enterotoxemia and enteritis in livestock via epsilon toxin production. In type D strain CN3718, CodY was previously shown to increase the level of epsilon toxin production and repress sporulation. C. perfringens type A strains producing C. perfringens enterotoxin (CPE) cause human food poisoning and antibiotic-associated diarrhea. Sporulation is critical for C. perfringens type A food poisoning since spores contribute to transmission and resistance in the harsh food environment and sporulation is essential for CPE production. Therefore, the current study asked whether CodY also regulates sporulation and CPE production in SM101, a derivative of C. perfringens type A food-poisoning strain NCTC8798. An isogenic codY-null mutant of SM101 showed decreased levels of spore formation, along with lower levels of CPE production. A complemented strain recovered wild-type levels of both sporulation and CPE production. When this result was coupled with the earlier results obtained with CN3718, it became apparent that CodY regulation of sporulation varies among different C. perfringens strains. Results from quantitative reverse transcriptase PCR analysis clearly demonstrated that, during sporulation, codY transcript levels remained high in SM101 but rapidly declined in CN3718. In addition, abrB gene expression patterns varied significantly between codY-null mutants of SM101 and CN3718. Compared to the levels in their wild-type parents, the level of abrB gene expression decreased in the CN3718 codYnull mutant strain but significantly increased in the SM101 codY-null mutant strain, demonstrating CodY-dependent regulation differences in abrB expression between these two strains. This difference appears to be important since overexpression of the abrB gene in SM101 reduced the levels of sporulation and enterotoxin production, supporting the involvement of AbrB repression in regulating C. perfringens sporulation.

show abstract

Section: Figmentioning

confidence: 58%

CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101

Freedman

Evans

et al. 2017

Infect Immun

View full text Add to dashboard Cite

show abstract

“…This approach, applied to the CodY regulator, involves mutating the effector binding site to mimic graded nutrient depletion, resulting in protein variants with fixed activation states along the full spectrum of CodY activity. Readers are directed to a recent review by Brinsmade (6) for a detailed summary of these studies. Comparison of the transcriptomes of cells bearing each protein variant has revealed that CodY-regulated genes are expressed as a hierarchy, whereby some target genes are derepressed upon a slight reduction of CodY activity, whereas other target genes remain repressed under the same conditions and are derepressed only upon a more significant reduction of CodY activity (3–5).…”

Section: Bacterial Adaptation To Nutrient Availabilitymentioning

confidence: 99%

“…pneumoniae (32), and Streptococcus pyogenes (45, 61–63). The role of CodY as a regulator of metabolism and virulence has been comprehensively reviewed elsewhere; thus, readers are directed to several recent reviews for more information (6, 24, 64, 65). …”

Section: Bcaas As Indicators Of Cellular Metabolic Statusmentioning

confidence: 99%

Branching Out: Alterations in Bacterial Physiology and Virulence Due to Branched-Chain Amino Acid Deprivation

Kaiser

Heinrichs

2018

mBio

View full text Add to dashboard Cite

The branched-chain amino acids (BCAAs [Ile, Leu, and Val]) represent important nutrients in bacterial physiology, with roles that range from supporting protein synthesis to signaling and fine-tuning the adaptation to amino acid starvation. In some pathogenic bacteria, the adaptation to amino acid starvation includes induction of virulence gene expression: thus, BCAAs support not only proliferation during infection, but also the evasion of host defenses.

show abstract

“…For instance, the branched-chain amino acid (BCAA) isoleucine seemed to be preferentially synthesized de novo by S. suis in CSF but not in blood. BCAA biosynthesis is a tightly transcriptionally regulated metabolic pathway in bacteria [14]. This prompted us to analyze the transcriptomic adaptation of S. suis in more detail.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Analysis Reveals Selective Metabolic Adaptation of Streptococcus suis to Porcine Blood and Cerebrospinal Fluid

et al. 2017

View full text Add to dashboard Cite

Streptococcus suis is a zoonotic pathogen that can cause severe pathologies such as septicemia and meningitis in its natural porcine host as well as in humans. Establishment of disease requires not only virulence of the infecting strain but also an appropriate metabolic activity of the pathogen in its host environment. However, it is yet largely unknown how the streptococcal metabolism adapts to the different host niches encountered during infection. Our previous isotopologue profiling studies on S. suis grown in porcine blood and cerebrospinal fluid (CSF) revealed conserved activities of central carbon metabolism in both body fluids. On the other hand, they suggested differences in the de novo amino acid biosynthesis. This prompted us to further dissect S. suis adaptation to porcine blood and CSF by RNA deep sequencing (RNA-seq). In blood, the majority of differentially expressed genes were associated with transport of alternative carbohydrate sources and the carbohydrate metabolism (pentose phosphate pathway, glycogen metabolism). In CSF, predominantly genes involved in the biosynthesis of branched-chain and aromatic amino acids were differentially expressed. Especially, isoleucine biosynthesis seems to be of major importance for S. suis in CSF because several related biosynthetic genes were more highly expressed. In conclusion, our data revealed niche-specific metabolic gene activity which emphasizes a selective adaptation of S. suis to host environments.

show abstract

CodY, a master integrator of metabolism and virulence in Gram-positive bacteria

Cited by 72 publications

References 113 publications

CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101

CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101

Branching Out: Alterations in Bacterial Physiology and Virulence Due to Branched-Chain Amino Acid Deprivation

Transcriptomic Analysis Reveals Selective Metabolic Adaptation of Streptococcus suis to Porcine Blood and Cerebrospinal Fluid

Contact Info

Product

Resources

About