PMID- 11553573
OWN - NLM
STAT- MEDLINE
DCOM- 20011025
LR  - 20181113
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 69
IP  - 10
DP  - 2001 Oct
TI  - Reassessing the role of Staphylococcus aureus clumping factor and 
      fibronectin-binding protein by expression in Lactococcus lactis.
PG  - 6296-302
AB  - Since Staphylococcus aureus expresses multiple pathogenic factors, studying their 
      individual roles in single-gene-knockout mutants is difficult. To circumvent this 
      problem, S. aureus clumping factor A (clfA) and fibronectin-binding protein A 
      (fnbA) genes were constitutively expressed in poorly pathogenic Lactococcus 
      lactis using the recently described pOri23 vector. The recombinant organisms were 
      tested in vitro for their adherence to immobilized fibrinogen and fibronectin and 
      in vivo for their ability to infect rats with catheter-induced aortic 
      vegetations. In vitro, both clfA and fnbA increased the adherence of lactococci 
      to their specific ligands to a similar extent as the S. aureus gene donor. In 
      vivo, the minimum inoculum size producing endocarditis in > or =80% of the rats 
      (80% infective dose [ID80]) with the parent lactococcus was > or =10(7) CFU. In 
      contrast, clfA-expressing and fnbA-expressing lactococci required only 10(5) CFU 
      to infect the majority of the animals (P < 0.00005). This was comparable to the 
      infectivities of classical endocarditis pathogens such as S. aureus and 
      streptococci (ID80 = 10(4) to 10(5) CFU) in this model. The results confirmed the 
      role of clfA in endovascular infection, but with a much higher degree of 
      confidence than with single-gene-inactivated staphylococci. Moreover, they 
      identified fnbA as a critical virulence factor of equivalent importance. This was 
      in contrast to previous studies that produced controversial results regarding 
      this very determinant. Taken together, the present observations suggest that if 
      antiadhesin therapy were to be developed, at least both of the clfA and fnbA 
      products should be blocked for the therapy to be effective.
FAU - Que, Y A
AU  - Que YA
AD  - Division of Infectious Diseases, Department of Internal Medicine, Centre 
      Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
FAU - Francois, P
AU  - Francois P
FAU - Haefliger, J A
AU  - Haefliger JA
FAU - Entenza, J M
AU  - Entenza JM
FAU - Vaudaux, P
AU  - Vaudaux P
FAU - Moreillon, P
AU  - Moreillon P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Adhesins, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Coagulase)
RN  - 0 (Fibronectins)
RN  - 0 (fibronectin-binding proteins, bacterial)
RN  - 9001-31-4 (Fibrin)
RN  - 9001-32-5 (Fibrinogen)
SB  - IM
MH  - Adhesins, Bacterial/genetics/*physiology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Bacterial Adhesion
MH  - Bacterial Proteins/genetics/*physiology
MH  - Blood Platelets/metabolism
MH  - Carrier Proteins/genetics/*physiology
MH  - Coagulase/genetics/*physiology
MH  - Disease Models, Animal
MH  - Endocarditis, Bacterial/*microbiology
MH  - Female
MH  - Fibrin/metabolism
MH  - Fibrinogen/metabolism
MH  - Fibronectins/metabolism
MH  - Gene Expression
MH  - Humans
MH  - Lactococcus lactis/genetics/*pathogenicity
MH  - Molecular Sequence Data
MH  - Rats
MH  - Rats, Wistar
MH  - *Staphylococcus aureus/genetics
PMC - PMC98764
EDAT- 2001/09/13 10:00
MHDA- 2001/10/26 10:01
PMCR- 2001/10/01
CRDT- 2001/09/13 10:00
PHST- 2001/09/13 10:00 [pubmed]
PHST- 2001/10/26 10:01 [medline]
PHST- 2001/09/13 10:00 [entrez]
PHST- 2001/10/01 00:00 [pmc-release]
AID - 0442 [pii]
AID - 10.1128/IAI.69.10.6296-6302.2001 [doi]
PST - ppublish
SO  - Infect Immun. 2001 Oct;69(10):6296-302. doi: 10.1128/IAI.69.10.6296-6302.2001.