TY - JOUR

T1 - Diversity, prevalence, and longitudinal occurrence of type II toxin-antitoxin systems of Pseudomonas aeruginosa infecting cystic fibrosis lungs

AU - Andersen, Sandra B.

AU - Ghoul, Melanie

AU - Griffin, Ashleigh S.

AU - Petersen, Bent

AU - Johansen, Helle K.

AU - Molin, Søren

PY - 2017

Y1 - 2017

N2 - Type II toxin-antitoxin (TA) systems are most commonly composed of two genes encoding a stable toxin, which harms the cell, and an unstable antitoxin that can inactivate it. TA systems were initially characterized as selfish elements, but have recently gained attention for regulating general stress responses responsible for pathogen virulence, formation of drug-tolerant persister cells and biofilms-all implicated in causing recalcitrant chronic infections. We use a bioinformatics approach to explore the distribution and evolution of type II TA loci of the opportunistic pathogen, Pseudomonas aeruginosa, across longitudinally sampled isolates from cystic fibrosis lungs. We identify their location in the genome, mutations, and gain/loss during infection to elucidate their function(s) in stabilizing selfish elements and pathogenesis. We found (1) 26 distinct TA systems, where all isolates harbor four in their core genome and a variable number of the remaining 22 on genomic islands; (2) limited mutations in core genome TA loci, suggesting they are not under negative selection; (3) no evidence for horizontal transmission of elements with TA systems between clone types within patients, despite their ability to mobilize; (4) no gain and limited loss of TA-bearing genomic islands, and of those elements partially lost, the remnant regions carry the TA systems supporting their role in genomic stabilization; (5) no significant correlation between frequency of TA systems and strain ability to establish as chronic infection, but those with a particular TA, are more successful in establishing a chronic infection.

AB - Type II toxin-antitoxin (TA) systems are most commonly composed of two genes encoding a stable toxin, which harms the cell, and an unstable antitoxin that can inactivate it. TA systems were initially characterized as selfish elements, but have recently gained attention for regulating general stress responses responsible for pathogen virulence, formation of drug-tolerant persister cells and biofilms-all implicated in causing recalcitrant chronic infections. We use a bioinformatics approach to explore the distribution and evolution of type II TA loci of the opportunistic pathogen, Pseudomonas aeruginosa, across longitudinally sampled isolates from cystic fibrosis lungs. We identify their location in the genome, mutations, and gain/loss during infection to elucidate their function(s) in stabilizing selfish elements and pathogenesis. We found (1) 26 distinct TA systems, where all isolates harbor four in their core genome and a variable number of the remaining 22 on genomic islands; (2) limited mutations in core genome TA loci, suggesting they are not under negative selection; (3) no evidence for horizontal transmission of elements with TA systems between clone types within patients, despite their ability to mobilize; (4) no gain and limited loss of TA-bearing genomic islands, and of those elements partially lost, the remnant regions carry the TA systems supporting their role in genomic stabilization; (5) no significant correlation between frequency of TA systems and strain ability to establish as chronic infection, but those with a particular TA, are more successful in establishing a chronic infection.

KW - Chronic infection

KW - Cystic fibrosis

KW - Genomic islands

KW - Infection

KW - Integrative and conjugative elements

KW - Longitudinal studies

KW - Pseudomonas aeruginosa

KW - Toxin-antitoxin system

U2 - 10.3389/fmicb.2017.01180

DO - 10.3389/fmicb.2017.01180

M3 - Journal article

AN - SCOPUS:85021237676

VL - 8

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

M1 - 1180

ER -