Bacterial bloodstream infections (bacteremia) are among the most common initiators of sepsis, a
leading cause of global morbidity and mortality. As such, it is critical to define host-pathogen
interactions that promote the effective clearance of bacteremia or facilitate bacterial evasion of
immune stress.
Our laboratory is specifically interested in Gram-negative bacteremia, which is increasingly difficult to
treat in clinics due to the antimicrobial resistance (AMR) crisis. Klebsiella pneumoniae is the second
leading cause of Gram-negative bacteremia and a major cause of healthcare-associated pneumonia.
K. pneumoniae is consistently classified as an urgent public health threat due to extensive AMR and
inclusion within the ESKAPE pathogens.
The pathogenesis of Gram-negative bacteremia involves three phases: 1) initial site infection, 2)
dissemination to the bloodstream, and 3) survival in blood filtering organs. Our research group
studies K. pneumoniae interactions with innate immunity at each of these phases in order to define
how this pathogen establishes such a virulent disease. Ultimately, we seek to define novel ways to
support innate immunity in the control of K. pneumoniae to prevent bacteremia and sepsis.
The main goal of the Holmes Lab is to understand host-pathogen interactions that underly K.
pneumoniae infection. We are particularly interested in mechanisms of Gram-negative bacteremia
pathogenesis and the onset of sepsis.
Research Interests
Ongoing areas of interest for the Holmes lab include:
1) investigating how K. pneumoniae evades immune stress
2) defining effective immune clearance of K. pneumoniae
3) characterizing the complex nature of the onset and containment of bacteremia using bacterial
barcoding approaches
4) understanding tissue-specific host-pathogen interactions
