The term adhesin has been described as a microbial surface component that mediates specific attachment to eukaryotic cell membrane and encompasses well known fimbriae as well as other poorly characterized and undefined structures. Adherence is facilitated by E. coli Fimbriae which are proteinaceous fibers on the bacterial cell wall. Fim-briae produce adhesins that bind to specic carbo-hydrate receptors present on uroepithelial cells (Beachey, 1981).

Many bacteria are known to be adhesive, attaching to and living in close association with various surfaces in their natural habitat. The ability of many pathogenic bacteria to adhere to specific host tissues is a factor of primary importance in diseases such as bacterial diarrhea, gonorrhea and Urinary Tract Infections. This specific adherence plays two important roles

1. It allows the bacteria to resist and circumvent the flushing and cleansing mechanisms that protect many epithelial surfaces in higher animals.

2. It determines the site of microbial infection by facilitating specific surface interaction between the bacteria and host epithelium.

Many studies (Fowler et al 1977, Kallenius et.al 1978) have shown that bacterial adherence is an essential virulence factor in the pathogenesis of community acquired Urinary Tract Infections. Duguid et al (1966) studied fimbriae of E.coli in great detail and classified them into three groups depending upon their haemagglutinating properties as the MSHA(Mannose Sensitive Haemagglutinating) type ,MRHA(Mannose Resistant Haemagglutinating) type and non-fimbrial haemagglutinin type.There is considerable evidence to support the use of cranberries for the prevention of urinary tract infections (Bodel et al., 1959; Moen, 1962; Sternlieb,1963; Papas et al., 1968; Avorn et al., 1994).

Cranberry juice acts by preventing adhesion which presumably helps urinary flushing of the causative bacteria, preventing their colonization of the urinary tract. This effect is achieved by inhibiting the infecting bacteria, Escherichia coli, from adhering to uroepithelial cells (Sobota, 1984; Schmidt and Sobota, 1988; Zafriri et al., 1989 Ofek et al., 1991). Bacterial adherence to mucosal cells plays a key role in the development of infection (Bea-chey, 1981)

Action of Cranberry proanthocyanidins:

• Alter E. coli's cell membranes

• Prevent the bacteria from making contact with cells or attaching to them even if they somehow manage to get close enough

• Change the shape of E.coli from rods to spheres

• Disrupt bacterial communication

Modelling of target protein was carried out using Swiss-PdbViewer (or SPDBV) and MODELLER 8V2. MODELLER was used for homology or comparative modeling of protein three-dimensional structures .Alignment of a sequence to be modeled is provided with known related structures and MODELLER automatically calculates a model containing all non-hydrogen atoms. MODELLER implements comparative protein structure modeling by satisfaction of spatial restraints ,and can perform many additional tasks, including de novo modeling of loops in protein structures, optimization of various models of protein structure with respect to a flexibly defined objective function, multiple alignment of protein sequences and/or structures, clustering, searching of sequence databases, comparison of protein structures, etc.

Validation of modelled structure was carried out using Structure Analysis and Validation Server. Structure Analysis and Validation Server greatly simplifies computational analysis of the molecular structure and sequence of proteins. The stereochemical validation of model structures of proteins is an important part of the comparative molecular modeling process.

Active sites present in the protein were identified using Q- SITE FINDER. It is an energy-based method for the prediction of protein-ligand binding sites designed by Laurie AT, Jackson RM.

Epicatechin a Proanthocyanidin from cranberry was selected as lead molecule for insilico analysis of its inhibition activity against modelled fimbrial adhesion .

Figure 1

Figure 1: Epicatechin a from cranberry

Docking analysis was carried out using AutoDock 4. Analysis of Epicatechin a Proanthocyanidin from cranberry as an inhibitor against modelled fimbrial adhesion was carried out using AUTODOCK. Further AUTODOCK was also used to visualize Interaction of Epicatechin with modelled fimbrial adhesion protein . Some of the commonly used antibiotics to treat urinary tract infections caused by Uropathogenic E.coli which includes Oflaxacin, sulfamethoxazole, Trimethoprim were subjected to docking analysis for comparative studies using AUTODOCK 4.

Figure 2

Table 1: Clustering Histogram of Various Conformations obtained for Epicatechin.

Figure 3

Figure 2: Interaction of Epicatechin a from cranberry with Modelled fimbrial adhesion virulence protein.

Figure 4

Figure 3: Interaction of Epicatechin a from cranberry with secondary structures of Modelled fimbrial adhesion virulence protein.

Some of the commonly used antibiotics to treat urinary tract infections caused by Uropathogenic E.coli which includes Oflaxacin, sulfamethoxazole, Trimethoprim were subjected to docking analysis for comparative studies. The Binding Energy values obtained for these antibiotics from docking analysis are as follows.

Figure 5

Table 2 : Binding Energy values of antibiotics commonly used for treatment of urinary tract infections caused by Uropathogenic

We thank Dr K.N Somasekharan, Dean, School of Chemical & Biotechnology, SASTRA UNIVERSITY, Mr Shivkumar , Mr Balamurugan ,SASTRA UNIVERSITY, Thanjavore, Tamilnadu, INDIA for their support.