Intracellular Bacterial Communities: A Potential Etiology for Chronic Lower Urinary Tract Symptoms

Abstract

Patients with persistent lower urinary tract symptoms and negative urine cultures are often difficult to treat. Infection may go undetected in these patients because the concentrations of bacteria in their urine are beneath the threshold of standard urine culture techniques. Empiric treatment may result in temporary relief, followed by recurrent symptoms. Occult and recurrent urinary tract infection may be due to both invasion of the bladder wall by uropathogenic Escherichia coli and the formation of biofilm-like intracellular bacterial communities. This review examines emerging evidence for a role of intracellular bacterial communities in human infection.

Figure 1

Fluorescence micrograph of uropathogenic Escherichia coli (green) growing as an intracellular bacterial community during experimental cystitis. A female mouse was transurethrally infected with UTI89 carrying a plasmid-encoded green fluorescent protein (green). The bladder was harvested, bisected, and fixed in 3% paraformaldehyde. The surface was visualized with wheat germ agglutinin (red), and the host nucleus was visualized with Hoechst (blue). (Color version available online).

Figure 2

Diagram including flow chart of clinical management of patients with lower urinary tract symptoms (LUTS) and corresponding cycle of intracellular bacterial community (IBC) maturation and development. Patients with an initial episode of LUTS will likely be diagnosed with a urinary tract infection by a primary care physician and treated with a course of antibiotics. If symptoms persist or recur and bother the patient, she will likely be referred to a urologist. This evaluation may include a combination of imaging, cystoscopy, or urodynamics, if indicated. If no structural or functional sources for symptoms are identified, the patient’s diagnosis is ultimately determined by the urine culture. The red half of the bladder (left half under “Culture +”) shows phases of IBC development, during which bacteria are in the intraluminal state in the bladder and a patient would be likely to have a positive urine culture with bacteria susceptible to antibiotics. The green half of the bladder (right half under “Culture −”) shows phases of IBC development during which bacteria are intracellular and a patient would be likely to have a negative urine culture with bacteria protected from antibiotic therapy. (Color version available online).