Dr Caro Kobras

Email:                   c.kobras@sheffield.ac.uk
Department:   Molecular Biology and Biotechnology (MBB)
Supervisor(s): Dr Andrew Fenton (MBB)
Collaborator Investigator(s): Prof Steven Renshaw
(Department of Infection, Immunity & Cardiovascular Disease)
                         
​Project:   Understanding mechanisms of antibiotic resistance in Streptococcus pneumoniae clinical isolates
The human pathogen Streptococcus pneumoniae is causative agent of many invasive diseases, including sepsis, meningitis and pneumonia. The so-called ‘pneumococcus’ is thus a major cause of morbidity and mortality worldwide, with highest infection rates among infants, elderly people and immunocompromised individuals. Pneumococcal infections are commonly treated by beta-lactam antibiotics, yet an alarmingly large number of pneumococcal isolates has developed resistance against this type of antibiotic, leaving treatment outcomes at risk. While development of pneumococcal conjugate vaccines lead to a short-term reduction of infections by resistant strains, antibiotic resistance rapidly emerged in isolates that are not covered by the vaccination program.

To counteract the continuous emergence of new antibiotic resistant lineages, it is important to understand the biological mechanisms underpinning beta-lactam resistance in S. pneumoniae. To this end, our project aims to identify novel genes linked to antibiotic resistance or tolerance using a whole genome fitness profiling approach (Tn-seq) in the presence of antibiotic selection. Once identified, the importance of candidate genes across the most prevalent clinical isolates will be assessed and the physiological role of the candidate genes examined. Based on these findings, we aim to elucidate the underlying mechanism that contributes to beta-lactam resistance. We will further test the impact of the identified resistance determinant on S. pneumoniae virulence using a zebrafish infection model. Ultimately, by targeting the mechanisms identified in this project, we hope to ‘re-sensitise’ antibiotic resistant pneumococcal strains to enable effective treatment of otherwise life-threatening infections. 
The Team
Management Team
Microbiology
Immunology
Clinicians
Allied Disciplines
PhD students
MSc students
Former Members
​and Alumni