Uropathogenic Escherichia coli: Urinary tract infections (UTI) are a major cause of morbidity in the United States, affecting at least seven million women and costing $2 billion per year. Uropathogenic Escherichia coli (UPEC) is responsible for 70% to 90% of these infections. Identification of E. coli as the cause of a UTI relies upon the number of bacteria in urine, with greater than 105 E. coli/ml of urine defined as an acute UTI. However, lower counts are difficult to interpret; as low as 102 E. coli/ml of urine can still indicate an infection, but their presence can also be due to contamination by commensal E. coli during sample isolation. Our goal is to characterize the UPEC phenotype in vitro, use bacterial genetics to identify the gene(s) associated with this phenotype, and use these genes as the basis for novel molecular diagnostic assays.
One phenotype we have found is that bladder epithelial cells secrete interleukin-6 (IL-6) and interleukin-8 (IL-8) in response to non-pathogenic E. coli, whereas they failed to do so in response to UPEC, indicating immune evasion or suppression. We speculate that UPEC must either evade or suppress this response effectively to colonize the bladder. We are currently attempting to identify the UPEC specific immunosuppressive factor, as we predict it will be a novel target for the development of assays to distinguish between commensal and uropathogenic E. coli.
Atopobium vaginae: Bacterial vaginosis (BV) is the most prevalent of all vaginal infections. Twenty to twenty five percent of women in the general population and 40% to 50% of women attending sexually transmitted disease (STD) clinics have BV. Bacterial vaginosis has been linked to upper genital tract complications such as preterm labor and delivery and pelvic inflammatory disease (PID). In addition, BV may facilitate the acquisition of STDs including the human immunodeficiency virus (HIV) and may be a risk factor for recurrent UTIs.
The diagnosis of BV is complicated by the fact that no single pathogenic organism has yet to be implicated as the cause of this syndrome. Instead, BV is characterized by an increase in the number of vaginal anaerobic Gram-positive and Gram-variable bacteria and a concomitant decline in the number of lactobacilli, particularly those lactobacillus species that produce hydrogen peroxide. Why these changes in vaginal flora occur is not known.
As with other complicated polymicrobial infections, it is highly likely that non-cultivable organisms play a role in BV. Atopobium vaginae (initially isolated and characterized in 1999) was recently shown to be associated with BV in epidemiological studies. Almost nothing is known, however, about the microbiology or pathogenesis of A. vaginae infections. Therefore, our goals are to define important parameters of A. vaginae microbiology such as growth requirements, production of potential virulence factors, and genetics that can be translated into a comprehensive model of A. vaginae pathogenesis in vivo. In parallel to that basic research, we will study the pathogenesis and epidemiology of A. vaginae infections with clinical studies focused on specific questions where improved diagnostics may benefit patients through better detection or treatment. |
