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 unrecognized pathways in persistent and multidrug-resistant infections. To this end, the group conducts mechanistic investigations, develops genetic and chemical 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 drug targets that are critical for bacterial survival in the host. One research focus involves the detection of adaptive mutations in patient specimens. The goal is to better understand host-specific selective pressures and to uncover bacterial vulnerabilities that can be exploited for targeted treatments. Another focus is on intracellular infection stages which are often refractory to conventional antibiotics. High-throughput infection screening assays with mutant libraries and compounds are employed to discover in vivo essential targets including both bacterial and host targets. The targets are validated in detailed mechanistic investigations with infection models to establish a foundation for the development of new antivirulence drugs and host-directed therapies.
The group is particularly interested in developing new approaches to more effectively treat urinary tract infections to prevent recurrence, reduce the risk of severe infection, and provide urgently needed options to treat extensively drug-resistant infections while preserving the microbiota (gut flora).
