## 3 Results and Discussion
### Cytokine Response of Normal Urothelial Cells
As observed from Table 3 and Supplementary Table S3A,B, only one statistically significant correlation was observed, namely between the high fold change group III and _cnf1_ gene. Some UPEC produce the chromosomally encoded toxin _cnf1_[38], which plays an important role in initiating infection, promoting inflammation [39] and generally increases the virulence of _E. coli_[40]. This infection often leads to inflammation [41], which in turn causes the production of pro-inflammatory cytokines [42], e.g., II-6, IL-8, and TNF-\(\alpha\)[43], which can also be observed from our results, as both UPEC strains DL18 and DL102 harboring the _cnf1_ gene caused the highest total cytokine production. Before we performed the Bonferroni correction, the _tcpC_ and _hlyA_ also correlated with the high fold change group III (_p_ value before correction of 0.0474, Supplementary Table S3A). TcpC-producing _E. coli_ use this host-defence-like protein to disrupt the innate immune response, among others (the IL-6 pathways), and cause inflammation and damage to the host's tissues [44]. In our study, most of the strains did not cause considerable change in the production of IL-6, including many strains that harbored the _tcpC_ gene (e.g., DL102). Alpha-hemolysin (HlyA) is cytotoxic to many types of cells and can cause tissue damage during urinary infections [45]. HlyA also promotes production of IL-6 and IL-8 in  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline  & & \multicolumn{6}{c}{**Total Cytokine Production Group**} \\ \cline{2-7}  & & \multicolumn{2}{c}{**Low Fold Change**} & \multicolumn{2}{c}{**Moderate Fold Change**} & \multicolumn{2}{c}{**High Fold Change**} \\  & & \multicolumn{2}{c}{**Group I**} & \multicolumn{2}{c}{**Group II**} & \multicolumn{2}{c}{**Group III**} \\  & & **(no. (\%))** & & **(no. (\%))** & & **(no. (\%))** & \\ \hline Virulence-associated & Group I & Non-Group I 1  & Group II & Non-Group III & Non-Group III \\ gene (no. (\%)) & (12 (50)) & (12 (50)) & (7 (29)) & (17 (71)) & (5 (21)) & (19 (79)) \\
**Toxins** & & & & & & \\ _cnf1_ & (7 (29)) & 1 (8) & 6 (50) & 2 (29) & 5 (29) & 4 (80) 4  & 3 (16) \\ _hlyA_ & (9 (38)) & 2 (17) & 7 (58) & 3 (43) & 6 (35) & 4 (80) & 5 (26) \\ _usp_ & (18 (75)) & 9 (75) & 9 (75) & 5 (71) & 13 (76) & 4 (80) & 14 (74) \\ _clbA_ & (12 (50)) & 4 (33) & 8 (67) & 4 (57) & 8 (47) & 4 (80) & 8 (42) \\ _pat_ & (14 (58)) & 6 (50) & 8 (67) & 4 (57) & 10 (59) & 4 (80) & 10 (53) \\
**Adhesins** & & & & & & & \\ _fimH_ & (23 (96)) & 12 (100) & 11 (92) & 6 (86) & 17 (100) & 5 (100) & 18 (95) \\ _papGII_ & (5 (21)) & 3 (25) & 2(17) & 1 (14) & 4 (24) & 1 (20) & 4 (21) \\ _papGIII_ & (7 (29)) & 2 (17) & 5 (42) & 2 (29) & 5 (29) & 3 (60) & 4 (21) \\ _afla/raBC_ & (0 (0)) & 0 (0) & 0 (0) & 0 (0) & 0 (0) & 0 (0) & 0 (0) \\ _sfaDE_ & (11 (46)) & 4 (33) & 7 (58) & 3 (43) & 8 (47) & 4 (80) & 7 (37) \\renal epithelial cells [46]. In our study, the majority of strains that encode HlyA induced production of IL-8. To sum up, [PERSON]'s exact test revealed that three prominent virulence-associated genes, _cnf1_, _hlyA_ and _tcpC_, correlated with the groups of strains that induced high total cytokine production by NPU cells in response to infection with these strains (above 3 fold change)--the high fold change group III. However, after we performed the Bonferroni correction, only the correlation of _cnf1_ with the high fold change group III remained statistically significant.