Methods of reducing virulence in bacteria

A pharmaceutical composition comprising a phenylpropanoid-type inhibitory compound according to formula (II) and a pharmaceutically-acceptable carrier or diluent:

• wherein R1 is an alkylene;
• R3 and R5 are hydrogen, R4 is hydrogen, hydroxy, sulfhydryl or halo, and R7 is hydroxy, carboxy or formyl;
• R3, R4, and R5 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, hydroxy, ether, alkoxy, acetal, hemiacetal, ketal, hemiketal, formyl, acyl, carboxy, thiocarboxy, thiolcarboxy, thionocarboxy, imidic acid, hydroxamic acid, ester, acyloxy, oxycarboyloxy, amino, amido, thioamido, acylamido, aminocarbonyloxy, ureido, guanidine, amindino, nitro, nitroso, azido, cyano, isocyano, isocyanato, thiocyano, isothiocyano, sulfhydryl, thioether, disulfide, sulfine, sulfonyl, sulfinic acid, sulfonic acid, sulfinate, sulfonate, sulfinyloxy, sulfonyloxy, sulfate, sulfamyl, sulfonamide, sulfamino, sulfonamino, sulfinamino, phosphino, phosphor, phosphinyl, phosphono, phosphonate, phosphonooxy, phosphate, phosphorous acid, phosphite, phosphoramidite, and phosphoramidate, wherein two of R3, R4, and R5 optionally are linked together to form a ring;
• and
• R7 is hydroxy, acetal, hemiacetal, ketal, hemiketal, formyl, acyl, carboxy, thiocarboxy, thiolcarboxy, thionocarboxy, imidic acid, hydroxamic acid, ester, acyloxy, oxycarboyloxy, amino, amido, thioamido, acylamido, aminocarbonyloxy, ureido, guanidine, amindino, nitro, nitroso, azido, cyano, isocyano, isocyanato, thiocyano, isothiocyano, sulfhydryl, thioether, disulfide, sulfine, sulfonyl, sulfinic acid, sulfonic acid, sulfinate, sulfonate, sulfinyloxy, sulfonyloxy, sulfate, sulfamyl, sulfonamide, sulfamino, sulfonamino, sulfinamino, phosphino, phosphor, phosphinyl, phosphono, phosphonate, phosphonooxy, phosphate, phosphorous acid, phosphite, phosphoramidite, or phosphoramidate.

A method of screening a compound for an ability to reduce virulence of a bacterium comprising at least one of a GacS/GacA-type system, a HrpX/HrpY-type system, a T3SS-type system, and a Rsm-type system, the method comprising:

• contacting the bacterium with a phenylpropanoid derivative;
• and
• detecting at least one of:
• (i) a change in a component of at least one of the GacS/GacA-type system, the HrpX/HrpY-type system, the T3SS-type system, and the Rsm-type system of the bacterium, and (ii) a change in host pathology.