Phage-associated mutator phenotype in group A streptococcus.
Defects in DNA mismatch repair (MMR) occur frequently in natural populations of pathogenic and commensal bacteria, resulting in a mutator phenotype. We identified a unique genetic element in Streptococcus pyogenes strain SF370 that controls MMR via a dynamic process of prophage excision and reintegration in response to growth. In S. pyogenes, mutS and mutL are organized on a polycistronic mRNA under control of a common promoter. Prophage SF370.4 is integrated between the two genes, blocking expression of the downstream gene (mutL) and resulting in a mutator phenotype. However, in rapidly growing cells the prophage excises and replicates as an episome, allowing mutL to be expressed. Excision of prophage SF370.4 and expression of MutL mRNA occur simultaneously during early logarithmic growth when cell densities are low; this brief window of MutL gene expression ends as the cell density increases. However, detectable amounts of MutL protein remain in the cell until the onset of stationary phase. Thus, MMR in S. pyogenes SF370 is functional in exponentially growing cells but defective when resources are limiting. The presence of a prophage integrated into the 5' end of mutL correlates with a mutator phenotype (10(-7) to 10(-8) mutation/generation, an approximately a 100-fold increase in the rate of spontaneous mutation compared with prophage-free strains [10(-9) to 10(-10) mutation/generation]). Such genetic elements may be common in S. pyogenes since 6 of 13 completed genomes have related prophages, and a survey of 100 strains found that about 20% of them are positive for phages occupying the SF370.4 attP site. The dynamic control of a major DNA repair system by a bacteriophage is a novel method for achieving the mutator phenotype and may allow the organism to respond rapidly to a changing environment while minimizing the risks associated with long-term hypermutability.
Scott
Julie
J
Department of Pharmaceutical Sciences, The University of Oklahoma College of Pharmacy, P.O. Box 26901, Oklahoma City, OK 73190, USA.
Thompson-Mayberry
Prestina
P
Lahmamsi
Stephanie
S
King
Catherine J
CJ
McShan
W Michael
WM
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D016680:Genome, Bacterial; D016685:Mitomycin / Q000494:pharmacology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D051719:MutS DNA Mismatch-Binding Protein / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D039002:Prophages / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017108:Streptococcus Phages / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000378:metabolism / Q000821:virology
D001426:Bacterial Proteins; D016685:Mitomycin; D000251:Adenosine Triphosphatases; D051719:MutS DNA Mismatch-Binding Protein