A self-lysis pathway that enhances the virulence of a pathogenic bacterium

Abstract

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of the alpA gene, which encodes a positive regulator that activates expression of the alpBCDE lysis cassette. Although this is lethal to the individual cell in which it occurs, we find it benefits the population as a whole during infection of a mammalian host. Thus, host and pathogen each may use PCD as a survival-promoting strategy. We suggest that activation of the Alp cell lysis pathway is a disease-enhancing response to bacterial DNA damage inflicted by the host immune system.

Non-hierarchical, RhlR-regulated acyl-homoserine lactone quorum sensing in a cystic fibrosis isolate ofPseudomonas aeruginosa

“…We found two genes of the alpBCDE lysis cassette, alpB and alpC , were repressed by RhlR in E90 under the conditions of our experiments. While induction of alpBCDE , via de-repression of the alpA gene, has been shown to be lethal to individual cells, it may benefit infecting cells at the population level [39]. We also observed down-regulation of the gene encoding the posttranscriptional regulatory protein RsmA by RhlR in E90.…”

Cell Death Pathway That Monitors Spore Morphogenesis

“…Indeed, the lysis of the mother cell at the end of sporulation represents an example of programmed cell death in a simple multicellular organism (the sporangium, consisting of just two cells: the mother cell and forespore). The existence of such altruistic examples of regulated cell death in independently growing bacteria and single-celled eukaryotes, though, has been controversial (56–58), especially since manifestations of this phenomenon are usually reported as a stress response of cells to an environmental insult rather than as a normal part of the cell cycle (59–61). A recent example of programmed cell death identified in the unicellular yeast Saccharomyces cerevisiae , though, suggested that during gametogenesis (also referred to as sporulation) aborted meiotic products that naturally arise are actively destroyed in a fashion that exhibits several key features of eukaryotic apoptosis, including genome fragmentation, in an effort to preserve the integrity of the germline (62).…”

A Quality-Control Mechanism Removes Unfit Cells from a Population of Sporulating Bacteria

“…Recent reports of “apoptotic-like” cell death in bacterial cells have added to the changing view of bacterial communities as more than simply a collection of independently operating cells, leading to speculation that unicellular organisms may initiate cell death to benefit the population as a whole (Bos et al, 2012; Dwyer et al, 2012; McFarland et al, 2015). Although specific mechanisms for cell death in these cases have been well characterized, the exact benefit of such an act to a single-celled organism has sometimes been difficult to explicitly demonstrate.…”