MtaR, a regulator of methionine transport, is critical for survival of group B streptococcus in vivo.
The group B streptococcus (GBS) is an important human pathogen that infects newborns as well as adults. GBS also provides a model system for studying adaptation to different host environments due to its ability to survive in a variety of sites within the host. In this study, we have characterized a transcription factor, MtaR, that is essential for the ability of GBS to survive in vivo. An isogenic strain bearing a kanamycin insertion in mtaR was attenuated for survival in a neonatal-rat model of sepsis. The mtaR mutant grew poorly in human plasma, suggesting that its utilization of plasma-derived nutrients was inefficient. When an excess of exogenous methionine (200 microg/ml) was provided to the mtaR mutant, its growth rate in plasma was restored to that of the wild-type strain. The mtaR mutant grew poorly in chemically defined medium (CDM) prepared with methionine at a concentration similar to that of plasma (4 microg/ml) but was able to grow normally in CDM prepared with a high concentration of methionine (400 microg/ml). Both the wild-type strain and the mtaR mutant were incapable of growth in CDM lacking methionine, indicating that GBS cannot synthesize methionine de novo. When the abilities of the strains to incorporate radiolabeled methionine were compared, the mtaR mutant incorporated fivefold less methionine than the wild-type strain during a 10-min period. Collectively, the results from this study suggest that the ability to regulate expression of a methionine transport system is critical for GBS survival in vivo.
Department of Pediatrics, Division of Infectious Disease, Childrens' Hospital and Regional Medical Center and University of Washington, Seattle, Washington 91805, USA.
Daniel
D
Shelver
Lakshmi
L
Rajagopal
Theresa O
TO
Harris
Craig E
CE
Rubens
D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008715:Methionine / Q000378:metabolism*; D009154:Mutation; D051381:Rats; D018805:Sepsis / Q000097:blood / Q000382:microbiology*; D013290:Streptococcal Infections / Q000097:blood / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D014157:Transcription Factors; C073470:LysR protein, Bacteria; D008715:Methionine