Compounds and methods for modulating bacterial functions
OwnerTony Romeo, Xin Wang +1inventors
InventorsTony Romeo, Xin Wang, Kazushi Suzuki
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Abstract
There is provided a method of reducing biofilm formation by biofilm-forming bacterial strains such as E. coli, Salmonella, Klebsiella, or a related gamma proteobacteria. CsrA activity levels in the cell may be modulated to impact biofilm formation and glycogen metabolism. CsrA levels may be modulated by modulating the expression of csrB RNA and UvrY and BarA gene products. By increasing levels of CsrB, BarA or SdiA in a bacterial cell or increasing the rate of UvrY phosphorylation, one can increase the levels of active UvrY in the strain. There is also provided a modulator of CsrA activity in a bacteria comprising a nucleotide sequence containing the sequence element CAGGAUG.
Claims44
A method of reducing biofilm formation by increasing CsrA levels in a biofilm-forming bacterial strain.
A method of increasing biofilm formation by decreasing CsrA levels in a biofilm-forming bacterial strain.
A method of increasing CsrB levels in a bacterial strain by increasing the levels of active UvrY in the strain.
A method of modulating biofilm formation in a biofilm-forming bacterial strain, comprising modulating the level of active UvrY in the strain.
A modulator of CsrA activity in a bacterial cell, said modulator comprising an isolated nucleotide sequence containing the sequence element CAGGAUG.
A method of increasing biofilm formation in a biofilm-forming bacterial strain, comprising inducing in that strain increased levels of a repeated nucleotide sequence, said sequence being CAGGAUG.
A method of increasing biofilm formation in a biofilm-forming bacterial strain, comprising increasing BarA levels or activity in the bacterial strain.
A method of decreasing biofilm formation in a biofilm-forming bacterial strain, comprising modulating UvrY phosphorylation.
A method of modulating biofilm formation in a bacterial strain, comprising modulating the expression level of uvrY in the strain.
A modulator of biofilm formation in a biofilm-forming bacterial strain, said modulator comprising an amino acid sequence selected from a portion of the amino acid sequence of CsrA shown to selectively bind RNA of biofilm-related genes under stringent conditions in vitro.
A method of modulating the expression of a RNA containing at least one of the nucleotide sequences UGCACACRRNYYGUGUGUG, UGCACACYYNRRGUGUGUG, UGCACACGGAUUGUGUGUG, and RNA sequences at least 90% homologous to at least one of these sequences, wherein Y represents a pyrimidine, R represents a purine and N represents either a purine or a pyrimidine, comprising providing an RNA binding agent specifically recognizing the sequence.
A CsrA binding agent comprising a RNA containing at least one of the nucleotide sequences UGCACACRRNYYGUGUGUG, UGCACACYYNRRGUGUGUG, UGCACACGGAUUGUGUGUG, or RNA sequences at least 90% homologous to at least one of these sequences, wherein Y represents a pyrimidine, R represents a purine and N represents either a purine or a pyrimidine and a physiologically acceptable carrier.
A method of identifying modulators of biofilm formation, comprising identifying agents which modulate the level of CsrA in a biofilm-forming bacterial strain.
An inhibitor of CsrA expression, comprising an isolated nucleotide sequence containing two or more repeats of the sequence element CAGGAUG.
A stimulator of biofilm formation, comprising an isolated sequence nucleotide containing two or more repeats of the sequence element CAGGAUG.
A modulator of biofilm formation, comprising an isolated amino acid sequence selected from a portion of the amino acid sequence of CsrA.
A method of modulating glycogen biosynthesis and catabolism in a bacterial strain comprising modulating the level or activity of CsrA.
A method of modulating glycogen biosynthesis in a biofilm-forming bacterial strain, comprising inducing the presence within the bacterial strain of a nucleotide having two or more repeats of the sequence CAGGAUG.
Use of an inhibitor of biofilm formation in improving recovery of a mammalian patient suffering from infection by bacteria forming biofilm.
A modulator of biofilm formation in a bacterial strain, comprising an agent having an AHL binding domain and a DNA binding domain and having at least 50% of the activity of sdiA in stimulating UvrA under physiological conditions.
Dependencies are inferred from the claim text.