UTIs are common in humans, resulting in an estimated 8 million outpatient visits and over $2 billion in health care costs in the United States each year. UTI is also one of the most common uses of antibiotics and likely a substantial contributor to the emergence of bacterial antibiotic resistance. The dominant etiologic agent of UTI in humans is uropathogenic Escherichia coli (UPEC), which accounts for up to 85% of community acquired UTIs. Investigators at the Center for Women's Infectious Disease Research have a long history of mechanistic studies of E. coli UTI pathogenic cascade. E. coli progresses through a series of distinct stages, from association with the bladder to the formation of intracellular biofilm-like communities, and release from this niche into the bladder lumen to allow re-infection of the epithelium. Our understanding of virulence mechanisms has allowed us to demonstrate novel therapeutic strategies. Promising avenues include anti-adhesion molecules targeting E. coli lectin FimH, small molecules capable of preventing biofilm formation, and the acquisition of iron through siderophores.
Metabolomic analysis of E. coli strains causing recurrent urinary tract infections found high levels of small molecules involved in iron scavenging called siderophores. These virulence-associated bacterial systems and the co-evolving host factors are the subjects of biochemical and microbiological studies using quantitative mass spectrometry, chemical biology, bacterial genetics, and mouse models of infection. Where network analysis identifies specific pathogenic mechanisms, rational drug design efforts are pursued with in silico small molecule docking. Together, these studies suggest new therapeutic and diagnostic strategies for recurrent urinary tract infections.
Biofilms are collections of microbes that adhere and aggregate. In many contexts, biofilms have been implicated in resistance to antibiotics, as well as the initiation and persistence of infection. In the urogenital tract, biofilm-like communities have been found to be essential processes in acute and chronic infections, making biofilms an important target for anti-microbial therapies.
Preterm birth contributes significantly to neonatal morbidity and mortality in the United States. The March of Dimes estimates that more than half a million babies are born prematurely in this country each year, 20% of which experience life-long disabilities such as severe lung problems, diabetes, heart disease, mental retardation, hearing loss, learning and behavioral problems, or cerebral palsy. A recent study estimated that preterm membrane rupture in pregnant women is associated with reproductive infection in up to 50% of cases. Investigators at the Center for Women’s Infectious Disease Research are interested in how specific bacterial infections trigger preterm birth, how infectious agents cause complications, and what we can do to prevent and treat these infections.
GBS (Streptococcus agalactiae) is the leading cause of neonatal sepsis and meningitis and a commensal of the lower gastrointestinal and vaginal mucosa. Current CDC guidelines recommend universal screening in pregnant women for GBS colonization and antibiotics during labor and delivery for carriers. Investigators at the Center for Women's Infectious Disease Research are interested in mechanisms of GBS colonization and infection and the possible impact of GBS on other infections and colonization of the female urogenital tract. While many virulence factors are important for GBS infection, the sialic-acid-containing capsular polysaccharide affects both systemic and urogenital infections by downregulating immune clearance via phagocytosis and oxidative burst.
BV is an imbalance of the vaginal flora characterized by diminished levels of beneficial lactobacilli and an overgrowth of various anaerobic bacteria. Reproductive age women with BV are more likely to experience infections of the placenta and amniotic fluid, preterm labor with delivery of premature low birth weight infants, increased susceptibility to sexually transmitted diseases including HIV, pelvic inflammatory disease, postpartum endometritis, and infertility. Despite the threat to the life and health of women and infants, BV is often overlooked and can be difficult to treat. While BV often initially responds to antibiotics, recurrences are common within a few weeks and occur in more than half of women within a year. Several studies report inconsistent results about whether antibiotic treatment for BV during pregnancy reduces the risk of preterm birth—in fact, some have shown that women treated with antibiotics are at even higher risk of delivering a preterm, low birth weight infant. Due to the lack of benefit from conventional antibiotic treatment, screening and preventative measures have not been enacted and BV continues to contribute to serious and life-threatening reproductive complications. Investigators at the Center for Women's Infectious Disease Research are defining underlying biochemistry and glycobiology that may contribute to the causes or complications of BV.
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