Host pathogen interactions in antibiotic-resistant and persistent infections
Prof. Ernst's working group operates at the interface of molecular microbiology, genomics, epidemiology and chemical biology to identify, investigate, and target unrecognised pathways in persistent and multidrug-resistant infections. To this end, the group conducts mechanistic investigations, develops genetic screens in infection related settings, and studies the adaptive evolution of pathogenicity and antibiotic tolerance to identify in vivo essential pathways in the context of persistent and multidrug-resistant infections. Insights from these studies provide a basis for the working group to explore unconventional antimicrobial strategies.
Antibiotic resistance has become a global threat to public health due to the emergence of extensively drug-resistant bacteria and the sharp decline in antibiotic discovery. In the most extreme cases, antibiotic resistance can lead to untreatable infections that result in persistent infections and high mortality rates.
However, persistent infections are also frequently caused by bacteria that display in vitro antibiotic susceptibility, illustrating the limitations of available antibiotics in the complex environment of the host and the need to develop new approaches to treat persistent infections. This is why Prof. Ernst’s working group is interested in understanding host pathogen interactions in multidrug-resistant and persistent infections caused by Klebsiella pneumoniae, one of the most concerning antibiotic resistance threats and a common cause of hospital-acquired infections.
The ultimate goal of the working group is translation: a better understanding of the pathogenicity of multidrug-resistant bacteria aims to create a basis for the development of new anti-infectives that are not classic antibiotics.
The researchers are working to identify genes that are important for bacterial survival in the host. One of the research areas involves patient specimens which are screened for adaptive mutations that promote persistent or more virulent infections. Mechanistic investigations with infection models are employed to gain a better understanding of the host-pathogen interface in multidrug-resistant infections, including a better understanding of disease progression that does not only include disease exacerbation and resolution but also persistent and recurrent infection.
The working group is particularly interested in understanding the molecular basis of recurrent urinary tract infections, including persistent intracellular stages of infection that may reveal general insights into persistent infections and antibiotic treatment failure.
