In the Lemos-Abranches lab, we investigate the molecular factors that mediate virulence in the opportunistic Gram-positive pathogens Streptococcus mutans and Enterococcus faecalis.
View research publications from our lab members from 1998-present.
As a major etiological agent of human dental caries, S. mutans resides primarily in biofilms that form on tooth surfaces, also known as dental plaque. In addition to caries, S. mutans is responsible for cases of infective endocarditis with a subset of strains that are capable to invade the intracellular compartment of host cells possibly involved in a number of other extraoral pathologies. Our studies with S. mutans have focused on understanding the molecular mechanisms the organism employs to colonize tooth surfaces, to rapidly metabolize a wide variety of carbohydrates obtained from the host diet, and to survive the numerous (and frequent) environmental challenges encountered in oral biofilms. In the first project, we are investigating how two global stress regulators, SpxA1 and SpxA2, mediate S. mutans oxidative and envelope stress survival. In the second project, we are characterizing the molecular mechanisms of metal homeostasis of S. mutans in order to determine the role of these mechanisms in the pathophysiology of S. mutans. Finally, in our third project, we are studying the collagen-binding protein Cnm, which mediates intracellular invasion and is present in a subset of strains. Specifically, we are investigating the association of Cnm with the persistence and virulence of S. mutans in the oral cavity, severe cases of infective endocarditis and, possibly, the development of other extraoral pathologies.
Despite being a harmless gut commensal in healthy individuals, enterococci (Enterococcus faecalis and E. faecium) are causative agents of opportunistic infections, especially in hospitalized patients with underlying diseases that impair the immune system, or patients undergoing prolonged antibiotic treatment. Known to produce a small number of the more typical virulence factors such as toxins and proteases, the virulence potential of enterococci largely derives from their capacity to withstand a variety of harsh conditions, subvert the immune system, and to form biofilms on tissue surfaces and indwelling devices. Our research efforts have been focused on characterizing the mechanisms by which E. faecalis respond to and survive under adverse conditions. In the first project, we are investigating how the signaling nucleotides (p)ppGpp and c-di-AMP promote stress survival, antibiotic persistence and virulence of E. faecalis. In the second project, we are using in vitro, ex vivo and in vivo approaches to determine the significance of metal homeostasis to E. faecalis pathophysiology.