While in transit within and between hosts, uropathogenic Escherichia coli (UPEC) encounters multiple stresses, including substantial levels of nitric oxide and reactive nitrogen intermediates. Here we show that UPEC, the primary cause of urinary tract infections, can be conditioned to grow at higher rates in the presence of acidified sodium nitrite (ASN), a model system used to generate nitrosative stress. When inoculated into the bladder of a mouse, ASN-conditioned UPEC bacteria are far more likely to establish an infection than nonconditioned bacteria. Microarray analysis of ASN-conditioned bacteria suggests that several NsrR-regulated genes and other stress-and polyamine-responsive factors may be partially responsible for this effect. Compared to K-12 reference strains, most UPEC isolates have increased resistance to ASN, and this resistance can be substantially enhanced by addition of the polyamine cadaverine. Nitrosative stress, as generated by ASN, can stimulate cadaverine synthesis by UPEC, and growth of UPEC in cadaverine-supplemented broth in the absence of ASN can also promote UPEC colonization of the bladder. These results suggest that UPEC interactions with polyamines or stresses such as reactive nitrogen intermediates can in effect reprogram the bacteria, enabling them to better colonize the host.The urinary tract is normally a sterile environment, and it is both hostile and poorly accessible to most microbes. However, roughly one-half of women in the United States experience a urinary tract infection (UTI) at least once in their lifetime, and one-quarter of affected women endure recurrence (22,25). More than 80% of UTIs are due to strains of uropathogenic Escherichia coli (UPEC), which are usually presumed to be part-time gut flora that have reached the urinary tract by ascension via the periurethral area (53). Transmission of UPEC among individuals occurs primarily by way of fecal-oral routes and, in some cases, may involve the ingestion of contaminated food products or sexual contact (15,23,33,40,41,57). In order to survive and disseminate, UPEC must be able to adapt to multiple environments and stresses both within and outside the host.When a UPEC infection occurs, recruitment of nitric oxide (NO)-producing neutrophils to the bladder is an important line of defense (26,48). Within hours of infection, the nitrite levels in the urine increase up to threefold, and eventually the levels of NO within the bladder are 30-to 50-fold higher than those in uninfected controls (39, 48). The high levels of NO are due in part to inducible NO synthase activity, which is upregulated within 6 h after infection (45). A role may also be played by endothelial NO synthase, which is upregulated and activated in the bladder mucosa by E. coli lipopolysaccharide (36) and by the bacteria themselves, which can produce NO with nitrite reductases under low-oxygen-tension conditions (12). NO is a precursor of a variety of reactive nitrogen intermediates (RNIs), such as peroxynitrite and nitrosothiols, which can inflict exten...