Abstract

Reconfiguring the quorum regulator SdiA In EHEC O157:H7 to curtail its invasion of Hep-2 cells via Qq SdiAm

Author(s): S.Adline Princy, Surasikha Rangarajan, R.S.Santhosh, V.Praveen Krishna, D.Bharath

Bacteria accomplish various tasks necessary for their survival through Quorum Sensing (QS), a Process that ensures synchronization of their activities at the genetic level, which brings about favourable phenotypic changes. Highly pathogenic organisms, such as Enterohaemmorrhagic E.coli (EHECO157:H7), useQS as an importantmechanismfor establishing virulence and biofilm formation in host cells. These infections lead to haemorrhagic colitis, which could progress to a clinically critical condition termed Haemolytic Uremic Syndrome (HUS). Earlier investigation of our research group has implicated that compounds derived fromMelia dubia, shows SdiA selective biofilminhibition of Uropathogenic E.coli (UPEC). One such compound, QQ SdiAM, was tested as an SdiA antagonist of EHEC O157:H7 strains. QQ SdiAM was found to be effective at low concentration (MBEC of 1 µg/ml), and the results of biochemical assays performed showed that it has potent anti biofilmactivity.Autoaggregation and cell surface Hydrophobicity reduced upon treatment, as did acid resistance. The % hemolytic activity also decreased in sdiA+ strain upon QQ SdiAM treatment. Swarming motility showed an increase upon treatment. Expression of FtsZ cell division protein decreased by 51% in sdiA+ strain. In all these tests, the compound showed little to no effect on the “sdiA strains. CLSM analysis of strains adhered to HEp-2 cells showed significant decrease in biofilmparameters such as thickness and biomass, in sdiA+ strain. The compound also had high % cell viability (92%) at its MBEC value. These results suggest not only that QQ SdiAM is a potent antagonist of SdiA, but it is an anti-biofilm compound as well.