Reflux in the Mouse Model of Urinary Tract Infection

Two studies recently published in Infection and Immunity involved a mouse model of ascending urinary tract infection (UTI) (1, 6). The inoculation conditions used in both studies, i.e., 20 to 50 μl of bacterial suspension inoculated into the bladder, had been found in a previous study from the same laboratory to produce immediate vesicoureteral reflux (VUR) in a substantial proportion of mice (2).

As recognized by these and other investigators, VUR should be avoided in the mouse model of UTI because it introduces bacteria directly into the upper urinary tract, thereby bypassing important proximal steps in pathogenesis (but in an uncontrolled fashion), and because it can cause hydrostatic injury to the renal parenchyma, thereby rendering the model unrepresentative of uncomplicated ascending UTI in humans (2, 3). The investigators’ previous study, in which VUR could be avoided only by reduction of the inoculum volume to 10 μl and inoculation into the urethra rather than the bladder (2), was cited for the methods used in the recent studies despite the use of larger volumes and inoculation into the bladder in the recent studies (1, 6).

High levels of kidney infection were observed in the recent studies (1, 6), whereas negligible levels were achieved in the investigators’ previous study with the same bacterial strain (strain 1677) when VUR-free inoculation conditions were used (2). This finding suggests that inoculation-induced VUR may have accounted for some or most of the kidney infections encountered in the recent studies, a possibility which calls into question the physiological relevance of the studies’ findings. Interpretation of results thus would be aided by knowledge of whether experiments were done to confirm that the inoculation conditions used did not induce immediate VUR. In addition, since others have documented that 25 to 50 μl can be inoculated into the mouse bladder without causing VUR (4, 5), whereas Hopkins et al. previously found this not to be the case (2), it would be of considerable value to current or future users of the mouse model to know what VUR-avoidance measures Hopkins et al. may have introduced since their previous study (2).