TY - JOUR
T1 - A self-lysis pathway that enhances the virulence of a pathogenic bacterium
AU - McFarland, Kirsty A.
AU - Dolben, Emily L.
AU - LeRoux, Michele
AU - Kambara, Tracy K.
AU - Ramsey, Kathryn M.
AU - Kirkpatrick, Robin L.
AU - Mougous, Joseph D.
AU - Hogan, Deborah A.
AU - Dove, Simon L.
PY - 2015/7/7
Y1 - 2015/7/7
N2 - 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 derepression 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.
AB - 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 derepression 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.
KW - Cell lysis
KW - Essential regulator
KW - Lung colonization
KW - Programmed cell death
KW - Pseudomonas aeruginosa
UR - http://www.scopus.com/inward/record.url?scp=84936803316&partnerID=8YFLogxK
U2 - 10.1073/pnas.1506299112
DO - 10.1073/pnas.1506299112
M3 - Article
C2 - 26100878
AN - SCOPUS:84936803316
SN - 0027-8424
VL - 112
SP - 8433
EP - 8438
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 27
ER -