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A truncation in the regulator RocA underlies heightened capsule expression in serotype M3 group A streptococci.

Lynskey NN, Turner CE, Heng LS, Sriskandan S - Infect. Immun. (2015)

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.

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The recent report from Cao et al. regarding hyper-virulence associated with M3 group A streptococcal (GAS) infections identified serotype-specific mutations in two important gene regulators, fasC and rivR... Hyper-encapsulation of serotype M18 strains has been attributed to a truncation mutation in RocA, a multifunctional regulator in GAS... We identified six single nucleotide polymorphisms (SNPs) in M3 rocA in comparison with rocA in M1 and, importantly, a single A deletion in a poly(A) septamer tract at nucleotide 1228... This single nucleotide deletion induced a premature stop codon after 1,251 bp, resulting in a truncated protein of 416 amino acids rather than 451 amino acids (Fig. 1)... Turner, T... Lamagni, M... Holden, S... Sriskandan, and A... Efstratiou, unpublished)... The mutation is also present in the two existing NCBI sequences of M3 GAS originating from the United States (MGAS315) and Japan (SSI-1)... We first corroborated the observation of Cao et al. and demonstrated that our M3 GAS expressed more capsule than M1 GAS, as expected (Fig. 2A)... Furthermore, expression of a single copy of full-length rocAM89 incorporated into the M3 chromosome reduced levels of capsule expression, demonstrating that the unique mutations in serotype M3 RocA underlie the heightened levels of capsule expression exhibited by strains of this serotype (Fig. 2C)... These data suggest that, in conjunction with the mutations in fasC and rivR identified by Cao et al., a truncation mutation in RocA may contribute to the association of M3 GAS with severe invasive infections and high mortality.

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Serotype M3 capsule expression is derepressed by RocA M3 truncation. (A) M3 GAS express more capsule than M1 (n = 5 strains/group); however, capsule levels in M3 GAS were reduced by overexpression of full-length RocA (B) or chromosomal integration of a single copy of full-length RocA (C). All strains were wild type for CovR/S. M3 strains contained serotype-specific mutations in fasC, rivR, and rocA; M1 strains were wild type for these regulators. Data represent means (plus standard deviations) of results from 3 or 4 individual experiments. ND, not detected (below the limit of detection); *, Mann-Whitney P < 0.05.
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Figure 2: Serotype M3 capsule expression is derepressed by RocA M3 truncation. (A) M3 GAS express more capsule than M1 (n = 5 strains/group); however, capsule levels in M3 GAS were reduced by overexpression of full-length RocA (B) or chromosomal integration of a single copy of full-length RocA (C). All strains were wild type for CovR/S. M3 strains contained serotype-specific mutations in fasC, rivR, and rocA; M1 strains were wild type for these regulators. Data represent means (plus standard deviations) of results from 3 or 4 individual experiments. ND, not detected (below the limit of detection); *, Mann-Whitney P < 0.05.

Mentions: We first corroborated the observation of Cao et al. and demonstrated that our M3 GAS expressed more capsule than M1 GAS, as expected (Fig. 2A). Subsequently, we showed that overexpression of full-length RocA amplified from M89 GAS (RocAM89) (2) was sufficient to reduce capsule expression to levels similar to those in M1 GAS (Fig. 2B). Furthermore, expression of a single copy of full-length rocAM89 incorporated into the M3 chromosome reduced levels of capsule expression, demonstrating that the unique mutations in serotype M3 RocA underlie the heightened levels of capsule expression exhibited by strains of this serotype (Fig. 2C). These data suggest that, in conjunction with the mutations in fasC and rivR identified by Cao et al., a truncation mutation in RocA may contribute to the association of M3 GAS with severe invasive infections and high mortality.


A truncation in the regulator RocA underlies heightened capsule expression in serotype M3 group A streptococci.

Lynskey NN, Turner CE, Heng LS, Sriskandan S - Infect. Immun. (2015)

Serotype M3 capsule expression is derepressed by RocA M3 truncation. (A) M3 GAS express more capsule than M1 (n = 5 strains/group); however, capsule levels in M3 GAS were reduced by overexpression of full-length RocA (B) or chromosomal integration of a single copy of full-length RocA (C). All strains were wild type for CovR/S. M3 strains contained serotype-specific mutations in fasC, rivR, and rocA; M1 strains were wild type for these regulators. Data represent means (plus standard deviations) of results from 3 or 4 individual experiments. ND, not detected (below the limit of detection); *, Mann-Whitney P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363422&req=5

Figure 2: Serotype M3 capsule expression is derepressed by RocA M3 truncation. (A) M3 GAS express more capsule than M1 (n = 5 strains/group); however, capsule levels in M3 GAS were reduced by overexpression of full-length RocA (B) or chromosomal integration of a single copy of full-length RocA (C). All strains were wild type for CovR/S. M3 strains contained serotype-specific mutations in fasC, rivR, and rocA; M1 strains were wild type for these regulators. Data represent means (plus standard deviations) of results from 3 or 4 individual experiments. ND, not detected (below the limit of detection); *, Mann-Whitney P < 0.05.
Mentions: We first corroborated the observation of Cao et al. and demonstrated that our M3 GAS expressed more capsule than M1 GAS, as expected (Fig. 2A). Subsequently, we showed that overexpression of full-length RocA amplified from M89 GAS (RocAM89) (2) was sufficient to reduce capsule expression to levels similar to those in M1 GAS (Fig. 2B). Furthermore, expression of a single copy of full-length rocAM89 incorporated into the M3 chromosome reduced levels of capsule expression, demonstrating that the unique mutations in serotype M3 RocA underlie the heightened levels of capsule expression exhibited by strains of this serotype (Fig. 2C). These data suggest that, in conjunction with the mutations in fasC and rivR identified by Cao et al., a truncation mutation in RocA may contribute to the association of M3 GAS with severe invasive infections and high mortality.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The recent report from Cao et al. regarding hyper-virulence associated with M3 group A streptococcal (GAS) infections identified serotype-specific mutations in two important gene regulators, fasC and rivR... Hyper-encapsulation of serotype M18 strains has been attributed to a truncation mutation in RocA, a multifunctional regulator in GAS... We identified six single nucleotide polymorphisms (SNPs) in M3 rocA in comparison with rocA in M1 and, importantly, a single A deletion in a poly(A) septamer tract at nucleotide 1228... This single nucleotide deletion induced a premature stop codon after 1,251 bp, resulting in a truncated protein of 416 amino acids rather than 451 amino acids (Fig. 1)... Turner, T... Lamagni, M... Holden, S... Sriskandan, and A... Efstratiou, unpublished)... The mutation is also present in the two existing NCBI sequences of M3 GAS originating from the United States (MGAS315) and Japan (SSI-1)... We first corroborated the observation of Cao et al. and demonstrated that our M3 GAS expressed more capsule than M1 GAS, as expected (Fig. 2A)... Furthermore, expression of a single copy of full-length rocAM89 incorporated into the M3 chromosome reduced levels of capsule expression, demonstrating that the unique mutations in serotype M3 RocA underlie the heightened levels of capsule expression exhibited by strains of this serotype (Fig. 2C)... These data suggest that, in conjunction with the mutations in fasC and rivR identified by Cao et al., a truncation mutation in RocA may contribute to the association of M3 GAS with severe invasive infections and high mortality.

Show MeSH
Related in: MedlinePlus