Søren Molin: Survival strategies in bacterial populations during persistent lung infections
- Date: Sep 9, 2019
- Time: 12:00 PM - 01:00 PM (Local Time Germany)
- Speaker: Søren Molin from the Technical University of Denmark in Lyngby
- For more information on the speaker, please see: https://www.dtu.dk/english/service/phonebook/person?id=1652&tab=1
- Location: MPI Plön
- Room: Lecture hall
- Host: Paul Rainey
Abstract:
Patients
suffering from the genetic disorder cystic fibrosis (CF) are
nearly always
infected with various microorganisms in their airways.
Investigations of the
very common infecting pathogen in CF – Pseudomonas
aeruginosa – have shown that these infections develop over
relatively short
time periods into persistent and eventually chronic infections
despite a
functional immune system and continuous treatment with several
antibiotics. Only
very limited high-level antibiotic resistance, however, appears
among clinical
isolates of these bacteria during the first decade of infection,
and it is
therefore important to identify alternative mechanisms employed by
P.
aeruginosa to persist in presence of antibiotics. Moreover,
in cases of
actual high-level resistance development in the bacteria derived
from the CF patients,
we frequently observe that the underlying mutations are different
from those,
which usually are considered to be the most common based on
laboratory
selection experiments. Such observations are important to consider
in
connection with attempts to develop bioinformatics based tools for
prediction
and diagnosis of antibiotic resistance.
I will
briefly summarize our knowledge about persistence mechanisms
unrelated to high-level
antibiotic resistance derived from investigations of CF clinical
isolates of P. aeruginosa.
I will further describe
in some detail a case of high-level resistance to aminoglycosides
associated
with collateral sensitivity to chloramphenicol. The associated
mutation in a
gene for a ribosomal protein is very distinct from usually
reported
aminoglycoside resistance mutations. High-resolution structural
analysis of the
ribosomes from this mutant strain offers explanations of most/all
of the
phenotypes connected with the mutation in the r-protein gene.