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Linnéa Polland- Institutionen för kliniska vetenskaper, Lund
Title: Gene expression profiling of respiratory pathogens: development during infection and the effect of antibiotic treatment
Main supervisor: Magnus Paulsson
Reviewers: Pontus Nordenfelt, Magnus Rasmussen
Abstract
Background
Pneumonia and other infections of the lower respiratory tract (LRTI’s) are the most common causes of death by infection, and the sixth leading cause of mortality for all ages. How bacteria function during the course of airway infections and antibiotic treatment have previously been studied in vitro, in animal experiments or cell lines and models, meant to reliably imitate the environment of the human respiratory tract. Previous studies have shown that there is a significant difference between the bacterial gene expression (GE) between bacterial cells grown in the laboratory and bacterial cells growing in the human lung. My research is focused on these differences, and on how bacteria adapt and change during actual human infection.
Research questions
What is the difference in bacterial GE between bacteria grown in vitro versus in vivo/ex vivo?
Are changes induced by antibiotic treatment reproducible by in vitro experiments?
Can new genes targetable for treatment be found by studying bacterial GE directly in human samples?
Preliminary results
In our published study, we saw clear differences in the gene expression of Haemophilus influenzae cells grown in vitro and cells studied directly in sputum samples from patients with pneumonia. Lab grown bacteria showed a homogenic transcriptomic profile, while the bacteria studied in the airway samples showed highly heterogenic GE changes. Although, certain stress response genes, genes involved in the procurement of iron and other trace metals, and genes involved in the production of nucleic acid-components, showed evident upregulation in the human samples.
In our next study (unpublished), we have studied the GE of H. influenzae before versus after the initiation of antibiotic treatment. Preliminary results show that changes in bacterial GE induced by antibiotics vary widely between different patients, and no apparent similarity is found.
Significance
To learn more about how bacteria actually function in the human lung could lead to better adapted or even new treatment options, which in turn could lead to a better prognosis in LRTI’s.
Published studies
Polland L, Rydén H, Su Y, Paulsson M. In vivo gene expression profile of Haemophilus influenzae during human pneumonia. Microbiol Spectr. 2023 Sep 14;11(5):e0163923.
Om evenemanget
Plats:
Seminarierummet på B14, B1441
Kontakt:
linnea [dot] polland [at] med [dot] lu [dot] se