Phenotypes selected during chronic lung infection in cystic fibrosis patients: implications for the treatment of Pseudomonas aeruginosa biofilm infections

TY - JOUR

T1 - Phenotypes selected during chronic lung infection in cystic fibrosis patients

T2 - implications for the treatment of Pseudomonas aeruginosa biofilm infections

AU - Ciofu, Oana

AU - Mandsberg, Lotte F

AU - Wang, Hengzhuang

AU - Høiby, Niels

N1 - © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

PY - 2012/7

Y1 - 2012/7

N2 - During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by genetic variation. Mucoidy, hypermutability and acquirement of mutational antibiotic resistance are important adaptive phenotypes that are selected during chronic P. aeruginosa infection. This review dicsusses the role played by these phenotypes for the tolerance of biofilms to antibiotics and show that mucoidy and hypermutability change the architecture of in vitro formed biofilms and lead to increase tolerance to antibiotics. Production of high levels of beta-lactamase impairs penetration of beta-lactam antibiotics due to inactivation of the antibiotic. In conclusion, these data underline the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis.

AB - During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by genetic variation. Mucoidy, hypermutability and acquirement of mutational antibiotic resistance are important adaptive phenotypes that are selected during chronic P. aeruginosa infection. This review dicsusses the role played by these phenotypes for the tolerance of biofilms to antibiotics and show that mucoidy and hypermutability change the architecture of in vitro formed biofilms and lead to increase tolerance to antibiotics. Production of high levels of beta-lactamase impairs penetration of beta-lactam antibiotics due to inactivation of the antibiotic. In conclusion, these data underline the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis.

KW - Anti-Bacterial Agents

KW - Biofilms

KW - Chronic Disease

KW - Cystic Fibrosis

KW - Humans

KW - Lung

KW - Phenotype

KW - Pseudomonas Infections

KW - Pseudomonas aeruginosa

KW - Selection, Genetic

KW - beta-Lactams

U2 - 10.1111/j.1574-695X.2012.00983.x

DO - 10.1111/j.1574-695X.2012.00983.x

M3 - Journal article

C2 - 22540844

SN - 2049-632X

VL - 65

SP - 215

EP - 225

JO - Pathogens and Disease

JF - Pathogens and Disease

IS - 2

ER -