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

Abstract

Significance Bacterial pathogens frequently use type 3 secretion systems (T3SS) to counteract host immune responses to infection. T3SS expression is associated with increased virulence of Pseudomonas aeruginosa in humans and in animal models, but T3SS-negative bacteria often are isolated from acutely and chronically infected patients. We tested whether T3SS-negative bacteria could “cheat” during mixed infections with T3SS-positive bacteria in a murine model of acute pneumonia. Bacterial cheating occurred in the inflamed lung but only when T3SS-positive bacteria secreted the phospholipase A 2 effector, Exotoxin U. Phenotypically T3SS-expressing and –non-expressing bacteria co-exist within P. aeruginosa populations, suggesting that bacterial cheating might allow T3SS-negative organisms to establish themselves within a host.

Long-term social dynamics drive loss of function in pathogenic bacteria

“…These exoproducts act as "public goods": products that are beneficial to the group but vulnerable to exploitation by cheats that reap the benefit without paying the cost (6). Understanding selection on public goods is clinically relevant, because many are virulence factors (7,8), and social interactions have also been shown experimentally to affect infection dynamics in vivo (9,10).…”

Bacterial Sphingomyelinases and Phospholipases as Virulence Factors

“…exoU/spcU-carrying strains show many signs of being clonally related, and even though the ancestral plasmid underwent deletions, full-length exoU and spcU are retained, suggesting a clonal expansion of the original plasmid recipient strain and the existence of environmental pressures selecting for the ability to secrete functional ExoU (142). It is speculated that the presence of ExoU-producing strains in environmental reservoirs might be maintained because ExoU kills amoebae, P. aeruginosa's natural predators (143)(144)(145), and thus provides a public aid for ExoUnegative bacteria (146).…”

“…ExoU expression plays a significant role in P. aeruginosa dissemination from lung tissue into the bloodstream (160), and mutant strains lacking a functional ExoU are more easily cleared than wild-type bacteria and therefore have a dramatically reduced pathogenicity in experimental acute pneumonia models (152,161,162). T3SS-negative P. aeruginosa benefits from the public good provided by ExoU-mediated killing of neutrophils during an experimental pulmonary infection (146). Furthermore, ExoU constitutes a virulence marker, since ExoU-expressing strains are significantly associated with bacteremia, more severe disease, higher complication rates, and greater mortality in pneumonia patients (132,163).…”

Sociomicrobiology and Pathogenic Bacteria

“…The system is essential for pathogenesis but the protein complex is thought to be costly to produce. Using a mouse model of lung infection by P. aeruginosa Czechowska and colleagues provide evidence for cheating by mutants lacking type III secretion [53]. Although these mutants fail to infect mice on their own, they do well when co-infected with type III positive isogenic strains at a 1:1 ratio.…”

“…The public goods in this case are likely the metabolic products released by the killing of eukaryotic host cells which should benefit all individuals in a bacterial population irrespective of which ones have a type III system. Type III secretion mutants are often found in patients with P. aeruginosa and the study proposed that their rise is due to cheating [53]. In the absence of a mechanism to protect against cheating, cheaters are fated to dominate and cooperation would be doomed to extinction.…”