ASB strains differentially attenuate UTI visceral pain.

<p>Modulation of UTI visceral pain by a panel of 16 ASB <i>E. coli</i> strains. A) Mice were infected with NU14 and then instilled with saline or ASB <i>E. coli</i> at PID1, and allodynia was quantified through PID7 (n = 6 for all groups). For clarity, timecourses of allodynia for all 17 conditions were divided among 3 panels. All 16 ASB strains attenuated NU14-induced pelvic pain compared to the saline treated group. B) The relative analgesic activity of ASB strains was arbitrary grouped according to the magnitude of analgesia: strains with analgesic relative to saline but increased allodynia from PID1 (black bars), those that exhibited no increase in allodynia from PID1 to less than 75% reduction in visceral pain from PID1 (white bars), and those that exhibited greater than 75% reduction (gray bars). C) Representative ASB strains from each group in (B) were used in serial infections at two-week intervals. Serial infection did not induce allodynia. Data are reported as the mean ± SEM.</p

ASB <i>E. coli</i> isolate 2–12 rapidly attenuates UTI visceral pain of diverse uropathogens.

<p>A) Allodynia was quantified daily in groups of sham– or NU14-infected mice that were then treated at PID1 with saline, a three-day course of ciprofloxacin, or a single dose of intravesical or intravaginal 2–12 as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109321#pone-0109321-g002" target="_blank">Figure 2A</a> (n = 8 in all groups except the 2–12 intravaginal group where n = 6). NU14-infected mice exhibited a significant decrease in pelvic pain 24 hours following treatment with 2–12 via the bladder or vaginal introitus (P<0.05). Allodynia was quantified in mice infected via transureathral catheter with <i>Proteus mirabilis</i> (PM1), <i>Enterocccus faecalis</i> (EF1) and <i>Klebsiella pneumoniae</i> (KP1) and then treated with a three-day course of ciprofloxacin initiated at PID1 or a single intravesical dose of 2–12 (n = 5). B) PM1 induced pelvic allodynia that was significantly attenuated on PID3 and PID4 by 2–12 treatment, relative to the ciprofloxacin or saline groups (P<0.05). C) EF1 induced allodynia that was significantly attenuated on PID2-PID4 by 2–12 treatment, relative to ciprofloxacin or saline groups (P<0.05). Allodynia was also significantly reduced on PID5–6 compared to the saline group (P<0.05). D) KP1 induced allodynia that was significantly attenuated on PID2 by 2–12 treatment, relative to ciprofloxacin or saline groups (P<0.05).</p

<i>E. coli</i> 83972 attenuates NU14 bacteriuria.

<p>A) Experimental scheme for assessing efficacy of a single administration of ASB therapy relative to 3-day course of ciprofloxacin (n = 5 for all groups). B) Mice infected with NU14 exhibited a significant decrease in NU14 bacteriuria 24 hours after initiation of ciprofloxacin (group C, back triangles, PID2, 4, 10), relative to saline-treated mice (group S, white triangles, *P<0.05). A single instillation of 83972 (group ASB, grey inverted triangles) also resulted in a significant decrease in NU14 bacteriuria after 24 hours (PID2, 4, 10, *P<0.05). C) Urinary 83972 for all three groups during the experiment. D and E) Bladder colonization on PID20 was not significantly different between the groups tested. Dashed lines represent limits of detection.</p

<i>E. coli</i> 83972 attenuates NU14-induced bacteriuria and pelvic pain.

<p>A) Referred visceral hyperalgesia was measured as responses to mechanical stimulation of the pelvic region with von Frey filaments of 5 intensities. Responses were quantified at baseline, PID1 following NU14 infection, and 24 hours following of saline (n = 5) or 83972 (n = 10) instillation (PID2). B) NU14-infected mice exhibited a significant decrease in allodynia 24 hours following 83972 instillation. C) Percent increase in allodynia from PID1 was 146.2% in saline-treated mice, but decreased by over 68.9% in 83972-treated mice (P<0.01). D) Mice treated with 83972 exhibited a significantly less NU14 bacteriuria compared to saline-treated mice (P<0.01). Dashed line represents limit of detection. E) At PID1, NU14-infected mice were instilled with saline into the bladder or 2% lidocaine in the bladder, vaginal introitus or colon. Allodynia was significantly reduced at 1 h after lidocaine into any compartment, relative to bladder saline (*P<0.05; n = 9 saline, n = 10 bladder lidocaine, n = 11 colon lidocaine, n = 12 vaginal lidocaine). F) NU14-infected mice exhibited increased allodynia 24 hours after bladder instillation of saline, relative to PID1 (n = 10). Allodynia was significantly decreased at 24 hours following 83972 instillation into the bladder, colon or vaginal introitus (*P<0.05, n = 10 all groups). Data are reported as the mean ± SEM (A–C, E & F).</p