## 4 Discussion
\begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Antibiotic** & **MIC** & **MIC\({}_{\text{met}}\)** & **FIC** & **MBEC** & **MBEC\({}_{\text{met}}\)** & **FIC** \\ \hline Ciprofloxacinacin & 2 \(\mu\)g/mL & 1 \(\mu\)g/mL & 0.5 & 128 \(\mu\)g/mL & 32 \(\mu\)g/mL & 0.25 \\ Cefoperazone & 64 \(\mu\)g/mL & 16 \(\mu\)g/mL & 0.25 & 1024 \(\mu\)g/mL & 256 \(\mu\)g/mL & 0.25 \\ Amoxicillin/Clavulinic & 256 \(\mu\)g/mL & 32 \(\mu\)g/mL & 0.125 & 2048 \(\mu\)g/mL & 512 \(\mu\)g/mL & 0.25 \\ \hline Imipenem & 4 \(\mu\)g/mL & 2 \(\mu\)g/mL & 0.5 & 8 \(\mu\)g/mL & 4 \(\mu\)g/mL & 0.5 \\ Gentamycin & 16 \(\mu\)g/mL & 16 \(\mu\)g/mL & 1 & 512 \(\mu\)g/mL & 256 \(\mu\)g/mL & 0.5 \\ Tetracycline & 64 \(\mu\)g/mL & 64 \(\mu\)g/mL & 1 & 2048 \(\mu\)g/mL & 1024 \(\mu\)g/mL & 0.5 \\ Chloramphenicol & 64 \(\mu\)g/mL & 16 \(\mu\)g/mL & 0.25 & 2048 \(\mu\)g/mL & 256 \(\mu\)g/mL & 0.125 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: The susceptibility of isolated _P. mirabilis_ to antibiotics in presence of Metronidazoleare (\(\frac{1}{4}\) MIC). antibiotic resistance of the persistent microbes in diabetic foot ulcers [10]. Our findings revealed a significant diminishing effect of metronidazolezole on _P. mirabilis_ motilities. Biofilm formation is characteristic feature of the life style of pathogenic bacteria; It is composed of embedded microbial cells in dynamic communities that accumulate either on abiotic or living surfaces [50, 51]. In sequential manner and after bacterial adhesion to surfaces, free floating vegetative cells start to produce extracellular polymeric substances which leads to irreversible attachment and entrapping of bacteria in biofilms [52]. The flagella-driven motilities are needed for _P. mirabilis_ adhesion, which followed by its colonization and biofilm formation [49, 53, 54]. In compliance with our previous findings that showed the inhibition effect of metronidazolezole on _P. mirabilis_ motilities; metronidazolezole is significantly reduced the adhesion of _P. mirabilis_ to both abiotic surfaces and epithelial cells and also significantly decreased the biofilm formation. Moreover, MICs and MBECs for the tested antibiotics were markedly lowered when combined with metronidazolezole (\(\frac{1}{4}\) MIC). The synergistic effect of metronidazoleze at sub-MIC when combined with tested antibiotics indicate that these antibiotics can be used to treat diabetic foot ulcers in lower concentration, which may decrease the side effects, the resistance development and costs. Molecular docking is one of the most widely applied approaches for the study of protein-ligand interactions and for drug discovery and development. Therefore, molecular docking studies were carried out to get structural insights into the interaction between metronidazolezole and _P. mirabilis_ QS proteins and the Zn-dependent receptor-binding domain of _P. mirabilis_ MR/P fimbial adhesin MrpH. Mannose Resistant Proteus like fimbie (MRP) that are encoded by mrpABCDEFGH] operon, are the most widely studied _P. mirabilis_ fimbie. MRP fimbiae are greatly essential for _P. mirabilis_ aggregation, biofilm formation and colonization in kidney and bladder [55, 56]. MrpH is one of the main virulence involved fimbial proteins in _P. mirabilis_[56]. In this study, we showed that metronidazoleze has a considerable affinity to the binding site of _P. mirabilis_ adhesin MrpH. The molecular docking results emphasize our earlier finding in which we observed the reduction of adhesion in presence of metronidazolezole. QS is signaling system which organize the bacterial pathogenesis and QS targeting is one of the efficient approaches to diminish microbial virulence [16, 17, 23]. We hypothesized that hindering of metronidazolezole to QS system and bacterial adhesion leads to diminishing of the _P. mirabilis_ virulence factors armory and help greatly in treating aggressive infections as diabetic foot ulcers. In this context, we examined the capability of metronidazoleze to antagonize the _P. mirabilis_ QS essential proteins.