The Campylobacter jejuni dccRS two-component system is required for optimal in vivo colonization but is dispensable for in vitro growth.
A Campylobacter jejuni two-component signal transduction system (TCSTS), designated dccR-dccS (diminished capacity to colonize; Cj1223c-Cj1222c), has been found to be important for in vivo colonization but dispensable for in vitro growth. A DeltadccR response regulator mutant generated using the virulent strain 81-176 background exhibited significantly reduced colonization of immunocompetent limited flora (I-LF) mice, severe combined immunodeficient limited flora (SCID-LF) mice, and 1-day-old chicks. A DeltadccS sensor kinase mutant was likewise defective for colonization in the I-LF mouse model. DeltadccR-infected SCID-LF mice also exhibited dramatically reduced inflammation relative to wild type-infected SCID-LF mice. Despite this diminished colonization capacity, the DeltadccRS mutants were indistinguishable from wild type for growth under numerous in vitro conditions as well as for various phenotypes. Microarray analysis identified several genes encoding putative periplasmic and membrane proteins as being regulated by this two-component system; binding of purified His-tagged DccR to the promoter region of two of these genes supports a direct protein-DNA interaction. A conserved repeat sequence was identified in the promoter regions of these genes and in three other promoter regions in the genome, including that of an operon encoding a putative type I secretion system. Two of the regulated target genes were found to be essential for optimal colonization. Both the two-component system and the putative regulated genes have uncharacterized homologues in other Campylobacter and Helicobacter spp., suggesting that they may perform an important function in colonization among a variety of related pathogenic species.
MacKichan
Joanna K
JK
Stanford University, Department of Microbiology and Immunology, Stanford, CA, USA. jmackich@itsa.ucsf.edu
Gaynor
Erin C
EC
Chang
Christopher
C
Cawthraw
Shaun
S
Newell
Diane G
DG
Miller
Jeff F
JF
Falkow
Stanley
S
D000222:Adaptation, Physiological; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology*; D002169:Campylobacter Infections / Q000382:microbiology*; D016123:Campylobacter jejuni / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D002645:Chickens; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D016998:Helicobacter / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D033903:Periplasmic Proteins / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D011401:Promoter Regions, Genetic; D018085:Regulon; D015398:Signal Transduction; D014774:Virulence / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics* / Q000502:physiology
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D033903:Periplasmic Proteins; D037521:Virulence Factors