Research
Human Breast Milk Research
Epidemiological data indicates nutrients, such as those found in human breast milk, have protective properties against a variety of neonatal infections.
Our recent work has focused on the identification and purification of human milk components that have antimicrobial activities against bacterial pathogens. Our work has shown that human milk oligosaccharides (HMOs) and human milk lactoferrin have the capacity to inhibit bacterial growth and biofilm formation. HMOs have potent utility to sensitize bacterial pathogens to antibiotics to which they were previously resistant. Additionally, lactoferrin can repress bacterial virulence at the host-pathogen interface.
Together, this work highlights critical antimicrobial features of human milk and indicates that human milk components could be leveraged as antimicrobial chemotherapeutic strategies.
Human Placental Macrophage Research
Our lab focuses on studying host-pathogen interactions, and one of the most important sentinel innate immune cells that can be found in the gravid reproductive tract are placental macrophages (or Hofbauer cells).
We have well-established protocols to procure placenta from healthy, term, non-laboring C-section births which we utilize to isolate placental macrophages for our host-pathogen interaction studies. Our recent work indicates that prostaglandin E2 and protein kinase D are critical mediators of the human placental macrophage response to GBS.
Additionally, we have shown that placental macrophages elaborate extracellular traps comprised of DNA and loaded with tissue-remodeling enzymes as an antimicrobial strategy to immobilize and control GBS infection. However, GBS can survive and replicate within host macrophages by deploying virulence factors that circumnavigate the antimicrobial challenges presented by the macrophage.
Perinatal Group B Streptococcus Infection Research
In order to better understand the molecular mechanisms that underpin GBS infections during pregnancy we have refined a robust mouse model of ascending vaginal GBS infection during pregnancy. This model is a critical tool which facilitates studying GBS pathogenesis in the context of pregnancy.
Our work with this model has elucidated critical antimicrobial and immunomodulatory roles that neutrophils and macrophages play in response to GBS infection, and we have utilized targeted mutagenesis of GBS as well as genetic complementation assays to elucidate the role that capsule, NADH peroxidase, and metal homeostasis play in GBS pathogenesis using this model.
Most importantly, our recent work in Nature Communications and Mbio reveals that GBS (a non-motile bacterium) uses a repertoire of virulence factors to survive within placental macrophages and highjack them as a Trojan horse to invade the gravid reproductive tract and cross the placenta and invade the developing fetus.
For updates on the latest published research from Dr. Gaddy’s lab click here.