Elimination of Chromosomal Island SpyCIM1 from Streptococcus pyogenes Strain SF370 Reverses the Mutator Phenotype and Alters Global Transcription

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dc.contributor.authorChristina Hendrickson
dc.contributor.authorChad W. Euler
dc.contributor.authorScott V. Nguyen
dc.contributor.authorMaliha Rahman
dc.contributor.authorKimberly A. McCullor
dc.contributor.authorCatherine J. King
dc.contributor.authorVincent A. Fischetti
dc.contributor.authorW. Michael McShan
dc.date.accessioned2017-03-05T22:55:25Z
dc.date.available2017-03-05T22:55:25Z
dc.date.issued2015-12-23
dc.descriptionThis work was made possible by an Oklahoma Center for the Advancement of Science and Technology (OCAST) grant HR11-133 and by NIH Grant Number R15A1072718 to WMM and NIH Grant AI11822 to VAF.en_US
dc.descriptionen_US
dc.description.abstractStreptococcus pyogenes chromosomal island M1 (SpyCIM1) integrates by site-specific recombination into the 5’ end of DNA mismatch repair (MMR) gene mutL in strain SF370SmR, blocking transcription of it and the downstream operon genes. During exponential growth, SpyCIM1 excises from the chromosome and replicates as an episome, restoring mutL transcription. This process is reversed in stationary phase with SpyCIM1 re-integrating into mutL, returning the cells to a mutator phenotype. Here we show that elimination of SpyCIM1 relieves this mutator phenotype. The downstream MMR operon genes, multidrug efflux pump lmrP, Holliday junction resolution helicase ruvA, and DNA base excision repair glycosylase tag, are also restored to constitutive expression by elimination of SpyCIM1. The presence of SpyCIM1 alters global transcription patterns in SF370SmR. RNA sequencing (RNA-Seq) demonstrated that loss of SpyCIM1 in the SpyCIM1 deletion mutant, CEM1Δ4, impacted the expression of over 100 genes involved in virulence and metabolism both in early exponential phase, when the SpyCIM1 is episomal, as well as at the onset of stationary phase, when SpyCIM1 has reintegrated into mutL. Among these changes, the up-regulation of the genes for the antiphagocytic M protein (emm1), streptolysin O (slo), capsule operon (hasABC), and streptococcal pyrogenic exotoxin (speB), are particularly notable. The expression pattern of the MMR operon confirmed our earlier observations that these genes are transcribed in early exponential phase but silenced as stationary phase is approached. Thus, the direct role of SpyCIM1 in causing the mutator phenotype is confirmed, and further, its influence upon the biology of S. pyogenes was found to impact multiple genes in addition to the MMR operon, which is a novel function for a mobile genetic element. We suggest that such chromosomal islands are a remarkable evolutionary adaptation to promote the survival of its S. pyogenes host cell in changing environments.en_US
dc.description.peerreviewYesen_US
dc.description.peerreviewnoteshttp://www.plosone.org/static/editorial#peeren_US
dc.identifier.citationHendrickson C, Euler CW, Nguyen SV, Rahman M, McCullor KA, King CJ, et al. (2015) Elimination of Chromosomal Island SpyCIM1 from Streptococcus pyogenes Strain SF370 Reverses the Mutator Phenotype and Alters Global Transcription. PLoS ONE 10(12): e0145884. doi:10.1371/journal.pone.0145884en_US
dc.identifier.doi10.1371/journal.pone.0145884en_US
dc.identifier.urihttp://hdl.handle.net/11244/49284
dc.language.isoen_USen_US
dc.publisherPLos One
dc.relation.ispartofseriesPLoS ONE 10(12): e0145884
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0145884
dc.rightsAttribution 3.0 United States
dc.rights.requestablefalseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/
dc.subjectOperons,Streptococcus pyogenes,Chromosomes,Gene expression,DNA transcription,Polymerase chain reaction,Point mutation,RNA sequencingen_US
dc.titleElimination of Chromosomal Island SpyCIM1 from Streptococcus pyogenes Strain SF370 Reverses the Mutator Phenotype and Alters Global Transcriptionen_US
dc.typeResearch Articleen_US

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