A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP.
Signature-tagged transposon mutagenesis of Salmonella with differential recovery from wild-type and immunodeficient mice revealed that the gene here named cdgR[for c-diguanylate (c-diGMP) regulator] is required for the bacterium to resist host phagocyte oxidase in vivo. CdgR consists solely of a glutamate-alanine-leucine (EAL) domain, a predicted cyclic diGMP (c-diGMP) phosphodiesterase. Disruption of cdgR decreased bacterial resistance to hydrogen peroxide and accelerated bacterial killing of macrophages. An ultrasensitive assay revealed c-diGMP in wild-type Salmonella with increased levels in the CdgR-deficient mutant. Thus, besides its known role in regulating cellulose synthesis and biofilm formation, bacterial c-diGMP also regulates host-pathogen interactions involving antioxidant defence and cytotoxicity.
Hisert
Katherine B
KB
Department of Microbiology and Immunology, Weill Medical College of Cornell University, and Program in Immunology and Microbial Pathogenesis, Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA.
MacCoss
Michael
M
Shiloh
Michael U
MU
Darwin
K Heran
KH
Singh
Shaneen
S
Jones
Roger A
RA
Ehrt
Sabine
S
Zhang
Zhaoying
Z
Gaffney
Barbara L
BL
Gandotra
Sheetal
S
Holden
David W
DW
Murray
Diana
D
Nathan
Carl
C
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004251:DNA Transposable Elements; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D016415:Sequence Alignment
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; C062025:bis(3',5')-cyclic diguanylic acid; D006861:Hydrogen Peroxide; D006152:Cyclic GMP