Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 May 27;111(21):7801-6. doi: 10.1073/pnas.1400782111. Epub 2014 May 12.

Cheating by type 3 secretion system-negative Pseudomonas aeruginosa during pulmonary infection.

Author information

1
Departments of Medicine and barbara.kazmierczak@yale.edu.
2
Departments of Medicine andGraduate Program in Molecular and Cell Biology, Quinnipiac University, Hamden, CT 06518.
3
Departments of Medicine and.
4
Departments of Medicine andMicrobial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520; and barbara.kazmierczak@yale.edu.

Abstract

The opportunistic pathogen Pseudomonas aeruginosa expresses a type 3 secretion system (T3SS) strongly associated with bacterial virulence in murine models and human patients. T3SS effectors target host innate immune mechanisms, and T3SS-defective mutants are cleared more efficiently than T3SS-positive bacteria by an immunocompetent host. Nonetheless, T3SS-negative isolates are recovered from many patients with documented P. aeruginosa infections, leading us to test whether T3SS-negative strains could have a selective advantage during in vivo infection. Mice were infected with mixtures of T3SS-positive WT P. aeruginosa plus isogenic T3SS-OFF or constitutively T3SS-ON mutants. Relative fitness of bacteria in this acute pneumonia model was reflected by the competitive index of mutants relative to WT. T3SS-OFF strains outcompeted WT PA103 in vivo, whereas a T3SS-ON mutant showed decreased fitness compared with WT. In vitro growth rates of WT and T3SS-OFF bacteria were determined under T3SS-inducing conditions and did not differ significantly. Increased fitness of T3SS-OFF bacteria was no longer observed at high ratios of T3SS-OFF to WT, a feature characteristic of bacterial cheaters. Cheating by T3SS-OFF bacteria occurred only when T3SS-positive bacteria expressed the phospholipase A2 effector Exotoxin U (ExoU). T3SS-OFF bacteria showed no fitness advantage in competition experiments carried out in immunodeficient MyD88-knockout mice or in neutrophil-depleted animals. Our findings indicate that T3SS-negative isolates benefit from the public good provided by ExoU-mediated killing of recruited innate immune cells. Whether this transient increase in fitness observed for T3SS-negative strains in mice contributes to the observed persistence of T3SS-negative isolates in humans is of ongoing interest.

PMID:
24821799
PMCID:
PMC4040582
DOI:
10.1073/pnas.1400782111
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center