Spectrum of Bacterial Colonization Associated with Urothelial Cells from Patients with Chronic Lower Urinary Tract Symptoms

Abstract

c Chronic lower urinary tract symptoms (LUTS), such as urgency and incontinence, are common, especially among the elderly, but their etiology is often obscure. Recent studies of acute urinary tract infections implicated invasion by Escherichia coli into the cytoplasm of urothelial cells, with persistence of long-term bacterial reservoirs, but the role of infection in chronic LUTS is unknown. We conducted a large prospective study with eligible patients with LUTS and controls over a 3-year period, comparing routine urine cultures of planktonic bacteria with cultures of shed urothelial cells concentrated in centrifuged urinary sediments. This comparison revealed large numbers of bacteria undetected by routine cultures. Next, we typed the bacterial species cultured from patient and control sediments under both aerobic and anaerobic conditions, and we found that the two groups had complex but significantly distinct profiles of bacteria associated with their shed bladder epithelial cells. Strikingly, E. coli, the organism most responsible for acute urinary tract infections, was not the only or even the main offending pathogen in this more-chronic condition. Antibiotic protection assays with shed patient cells and in vitro infection studies using patient-derived strains in cell culture suggested that LUTS-associated bacteria are within or extremely closely associated with shed epithelial cells, which explains how routine cultures might fail to detect them. These data have strong implications for the need to rethink our common diagnoses and treatments of chronic urinary tract symptoms.

TLR2 Stimulation Regulates the Balance between Regulatory T Cell and Th17 Function: A Novel Mechanism of Reduced Regulatory T Cell Function in Multiple Sclerosis

“…In particular, most in vivo relevant lipopeptides are triacylated and, therefore, are adequately modeled by Pam3Cys used in our study (28,64). Respiratory viruses that can activate TLR2 (29,63) also have been associated with MS exacerbations (31,32,61). In addition, EBV, which is strongly associated with MS susceptibility (30), is able to activate the transcription factor NF-kB and the production of the chemokine CCL2 in a TLR2-dependent manner (65,66).…”

“…Our present findings provide a possible link between urinary and respiratory infections and T cell dysregulation that may lead to MS clinical exacerbations (relapses) (31,32,61,62), because the cell walls or outer membranes of Gram-negative bacteria, such as Escherichia coli, as well as Staphylococcus saprophyticus and other Gram-positive bacteria, which are typically involved (61,62), contain TLR2 agonists (29,63). In particular, most in vivo relevant lipopeptides are triacylated and, therefore, are adequately modeled by Pam3Cys used in our study (28,64).…”

An encapsulated drug delivery system for recalcitrant urinary tract infection

“…We chose this species because it is the most invasive bacteria seen in our patient group [6]. Briefly, fresh liquid cultures of bacteria were challenged with a dilution series of the drug capsules, compared with a similar series of control capsules and with injectiongrade unencapsulated gentamicin solution used in clinical practice.…”

“…Shielded from the host immune system and from antibiotics in the bladder lumen, such bacterial reservoirs can persist and later emerge to initiate a fresh round of acute infection [4]. Recent studies have shown that UTI is also associated with other species of chronic, invasive bacteria besides E. coli, including Enterococcus faecalis [5][6][7].…”

The Association between Chronic Inflammation and Recurrent Cystitis in Women

“…Their findings suggested that women with recurrent UTI should endure evaluation and treatment of episodes of infection to prevent the development of oversensitive detrusor. Other studies showed that positive urine culture at 10 5 CFU/ml in women is significantly associated with lower urinary tract symptoms, such as nocturia, urgency, urgency incontinence, and nocturnal enuresis [21,22]. Additionally, bacteriuria is also associated with bladder pain.…”