UTIs, E. COLI ABUs, AND UPEC Mucosal surfaces in the intestinal, respiratory, and urogen- ital tracts are populated by a highly diverse bacterial flora. Most host-dwelling bacteria are commensals and maintain a symbiotic relationship with the host; however, a minority are pathogens that attack the mucosa, causing tissue damage and disease symptoms. Bacterial pathogens differ from commensals by the expression of specific virulence factors, such as those that mediate tissue assault. Commensals, in contrast, have gen- erally been regarded as bacteria lacking such virulence factors or other specific mechanisms for interaction with host tissues. Asymptomatic carriage of bacteria may also result after a pri- mary symptomatic infection. However, this type of carrier state differs from commensalism in that variants of pathogenic strains persist without evoking a host response. This review is focused on the molecular basis for attenuation of virulence and adaptation to commensalism, using the prototypic asymptom- atic bacteriuria strain Escherichia coli 83972 as a model. Most E. coli strains coexist peacefully with their human host, while others cause disease. E. coli is a versatile pathogen caus- ing a spectrum of diseases, including urinary tract infections (UTIs), diarrhea, sepsis, and meningitis (28). UTIs are among the most common infectious diseases of humans and are a major cause of morbidity. It is estimated that 40 to 50% of healthy adult women have experienced at least one UTI epi- sode (15). Acute pyelonephritis and asymptomatic bacteriuria (ABU) represent the two extremes of UTI. Escherichia coli is responsible for 80% of UTIs. Acute pyelonephritis is a se- vere acute systemic infection caused by uropathogenic E. coli (UPEC) clones with virulence genes clustered on "pathogenic- ity islands" (13, 16, 25, 46, 67, 72). ABU, on the other hand, is an asymptomatic carrier state that resembles commensalism. Paradoxically, a large proportion of UTIs are caused by ABU E. coli. Individuals infected with ABU group E. coli may carry high urine titers of a single E. coli strain for months or years without provoking a host response. According to conventional notions, pathogens can develop from commensals by the ac- quisition of virulence-associated genes located on, for example, pathogenicity islands or plasmids. The flip side of this evolu- tionary force is the equally important adaptation of the newly minted pathogen to its new host niche, where genes are inac- tivated by either point mutation, insertion, or deletion (39). Here we illustrate such an example, where the commensal-to- pathogen shift in E. coli is bidirectional.