Impact of immunization against SpyCEP during invasive disease with two streptococcal species: Streptococcus pyogenes and Streptococcus equi

ABSTRACT The transcriptional regulator Rgg of Streptococcus pyogenes is essential for expression of the secreted cysteine protease SpeB. Although all isolates of S. pyogenes possess the speB gene, not all of them produce the protein in vitro. In a murine model of infection, the absence of SpeB production is associated with invasive disease. We speculated that naturally occurring mutations in rgg, which would also abrogate SpeB production, may be present in invasive isolates of S. pyogenes. Examination of the inferred Rgg sequences available in public databases revealed that the rgg gene in strain MGAS315 (a serotype M3 strain associated with invasive disease) encodes a proline at amino acid position 103 (Rgg103P); in contrast, all other strains encode a serine at this position (Rgg103S). A caseinolytic assay and Western blotting indicated that strain MGAS315 does not produce SpeB in vitro. Gene-swapping experiments showed that the rgg gene of MGAS315 is solely responsible for the lack of SpeB expression. In contrast to Rgg103S, Rgg103P does not bind to the speB promoter in gel shift assays, which correlates with a lack of speB expression. Despite its inability to activate speB expression, Rgg103P retains the ability to bind to DNA upstream of norA and to influence its expression. Overall, this study illustrates how variation at the rgg locus may contribute to the phenotypic diversity of S. pyogenes.

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Transcription of the Streptococcus pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated by Previously Unknown Upstream Elements

Infection and Immunity ◽

10.1128/iai.02035-14 ◽

2014 ◽

Vol 82 (12) ◽

pp. 5293-5307 ◽

Cited By ~ 19

Author(s):

Marina Falaleeva ◽

Oliwia W. Zurek ◽

Robert L. Watkins ◽

Robert W. Reed ◽

Hadeel Ali ◽

...

Keyword(s):

Hyaluronic Acid ◽

Streptococcus Pyogenes ◽

Regulatory Region ◽

Regulatory System ◽

Invasive Disease ◽

Negative Regulator ◽

Mobility Shift ◽

Putative Promoter ◽

Transcriptional Terminator ◽

Content Type

ABSTRACTThe important human pathogenStreptococcus pyogenes(group AStreptococcus[GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that thehasABCoperon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an intrinsic transcriptional terminator that inefficiently terminates HasS, permitting read-through transcription ofhasABC, and a putative promoter which lies upstream of P2. Electrophoretic mobility shift assays, quantitative reverse transcription-PCR, and transcriptional reporter data identified CovR as a negative regulator of P2. We found that the P1 and P2 promoters are completely repressed by CovR, and capsule expression is regulated by the putative promoter upstream of P2. Deletion ofhasSor of the terminator eliminates CovR-binding sequences, relieving repression and increasing read-through,hasAtranscription, and capsule production. Sequence analysis of 44 GAS genomes revealed a high level of polymorphism in the HasS sequence region. Most of the HasS variations were located in the terminator sequences, suggesting that this region is under strong selective pressure. We discovered that the terminator deletion mutant is highly resistant to neutrophil-mediated killing and is significantly more virulent in a mouse model of GAS invasive disease than the wild-type strain. Together, these results are consistent with the naturally occurring mutations in this region modulating GAS virulence.

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Comparative In Vitro Activity Profile of Oritavancin against Recent Gram-Positive Clinical Isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00952-09 ◽

2009 ◽

Vol 53 (11) ◽

pp. 4762-4771 ◽

Cited By ~ 50

Author(s):

Francis F. Arhin ◽

Deborah C. Draghi ◽

Chris M. Pillar ◽

Thomas R. Parr ◽

Gregory Moeck ◽

...

Keyword(s):

Streptococcus Pyogenes ◽

Resistance Rate ◽

Vitro Activity ◽

In Vitro Activity ◽

Activity Profile ◽

Coagulase Negative Staphylococci ◽

Gram Positive ◽

Streptococcal Species ◽

Resistance Rates

ABSTRACT Oritavancin activity was tested against 15,764 gram-positive isolates collected from 246 hospital centers in 25 countries between 2005 and 2008. Organisms were Staphylococcus aureus (n = 9,075), coagulase-negative staphylococci (n = 1,664), Enterococcus faecalis (n = 1,738), Enterococcus faecium (n = 819), Streptococcus pyogenes (n = 959), Streptococcus agalactiae (n = 415), group C, G, and F streptococci (n = 84), and Streptococcus pneumoniae (n = 1,010). Among the evaluated staphylococci, 56.7% were resistant to oxacillin. The vancomycin resistance rate among enterococci was 21.2%. Penicillin-resistant and -intermediate rates were 14.7% and 21.4%, respectively, among S. pneumoniae isolates. Among nonpneumococcal streptococci, 18.5% were nonsusceptible to erythromycin. Oritavancin showed substantial in vitro activity against all organisms tested, regardless of resistance profile. The maximum oritavancin MIC against all staphylococci tested (n = 10,739) was 4 μg/ml; the MIC90 against S. aureus was 0.12 μg/ml. Against E. faecalis and E. faecium, oritavancin MIC90s were 0.06 and 0.12, respectively. Oritavancin was active against glycopeptide-resistant enterococci, including VanA strains (n = 486), with MIC90s of 0.25 and 1 μg/ml against VanA E. faecium and E. faecalis, respectively. Oritavancin showed potent activity against streptococci (n = 2,468); MIC90s for the different streptococcal species were between 0.008 and 1 μg/ml. These data are consistent with previous studies with respect to resistance rates of gram-positive isolates and demonstrate the spectrum and in vitro activity of oritavancin against a wide variety of contemporary gram-positive pathogens, regardless of resistance to currently used drugs. The data provide a foundation for interpreting oritavancin activity and potential changes in susceptibility over time once oritavancin enters into clinical use.

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Dissemination of the Phage-Associated Novel Superantigen Gene speL in Recent Invasive and Noninvasive Streptococcus pyogenes M3/T3 Isolates in Japan

Infection and Immunity ◽

10.1128/iai.70.6.3227-3233.2002 ◽

2002 ◽

Vol 70 (6) ◽

pp. 3227-3233 ◽

Cited By ~ 60

Author(s):

Tadayoshi Ikebe ◽

Akihito Wada ◽

Yoshishige Inagaki ◽

Kumiko Sugama ◽

Rieko Suzuki ◽

...

Keyword(s):

Nucleotide Sequence ◽

Streptococcus Pyogenes ◽

Phage Particle ◽

Attachment Site ◽

Temperate Phage ◽

Invasive Infection ◽

Particle Fraction ◽

Toxic Shock ◽

Terminal Part ◽

Streptococcus Equi

ABSTRACT In Japan, more than 10% of streptococcal toxic shock-like syndrome (TSLS) cases have been caused by Streptococcus pyogenes M3/T3 isolates since the first reported TSLS case in 1992. Most M3/T3 isolates from TSLS or severe invasive infection cases during 1992 to 2001 and those from noninvasive cases during this period are indistinguishable in pulsed-field gel electropherograms. The longest fragments of these recent isolates were 300 kb in size, whereas those of isolates recovered during or before 1973 were 260 kb in size. These 260- and 300-kb fragments hybridized to each other, suggesting the acquisition of an about 40-kb fragment by the recent isolates. The whole part of the acquired fragment was cloned from the first Japanese TSLS isolate, NIH1, and its nucleotide sequence was determined. The 41,796-bp fragment is temperate phage φNIH1.1, containing a new superantigen gene speL near its right attachment site. The C-terminal part of the deduced amino acid sequence of speL has 48 and 46% similarity with well-characterized erythrogenic toxin SpeC and the most potent superantigen, SmeZ-2, respectively. None of 10 T3 isolates recovered during or before 1973 has speL, whereas all of 18 M3/T3 isolates recovered during or after 1992 and, surprisingly, Streptococcus equi subsp. equi ATCC 9527 do have this gene. Though plaques could not be obtained from φNIH1.1, its DNA became detectable from the phage particle fraction upon mitomycin C induction, showing that this phage is not defective. A horizontal transfer of the phage carrying speL may explain the observed change in M3/T3 S. pyogenes isolates in Japan.

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Molecular characterization of invasive and non-invasive Streptococcus pyogenes isolates from Romania

Journal of Medical Microbiology ◽

10.1099/jmm.0.2008/001875-0 ◽

2008 ◽

Vol 57 (11) ◽

pp. 1354-1363 ◽

Cited By ~ 12

Author(s):

Bogdan Luca-Harari ◽

Monica Straut ◽

Silvia Cretoiu ◽

Maria Surdeanu ◽

Vasilica Ungureanu ◽

...

Keyword(s):

Streptococcus Pyogenes ◽

Tetracycline Resistance ◽

Epidemiological Data ◽

Invasive Disease ◽

Reference Laboratory ◽

Non Invasive ◽

Serum Opacity Factor ◽

Fibronectin Binding Protein ◽

Resistance Rates ◽

And Control

In 2002, the Romanian National Reference Laboratory was invited to join the Strep-EURO project to study invasive Streptococcus pyogenes infections. During 2003 and 2004, a total of 33 isolates recovered from invasive disease were received from eight Romanian counties. For comparison, 102 isolates from non-invasive disease, as well as a collection of 12 old invasive strains (isolated between 1967 and 1980) were included. All isolates were characterized by several methods: T and emm typing, presence of the fibronectin-binding protein F1 gene (prtF1), serum opacity factor (sof), and superantigen (SAg) genes (speA, speB, speC, speF, speG, speH, ssa and smeZ). The recent invasive isolates exhibited 19 emm-types, of which emm1, emm81, emm76, emm49 and emm78 covered 57 % of the strains. Furthermore, multilocus sequence typing analysis revealed nine new sequence types, corresponding to emm types 1, 12, 49, 81, 92, 100, 106 and 119. The non-invasive isolates comprised 24 different emm types with a predominance of emm1 and 12; the old invasive strains were of eight emm types, of which four were unique for this group. All isolates harboured speB and speF; smeZ was detected in all invasive strains, except for the emm49 and emm81 isolates. The majority of isolates from carriers, and patients with pharyngitis were prtF1 positive, most of these (14 strains) being emm12. High tetracycline resistance rates were noted among both invasive and control isolates (54 % and 35 %, respectively), whereas macrolide resistance rates were low (3 % and 5 %, respectively). Active and continuing surveillance is required to provide an accurate assessment of the disease burden and to provide epidemiological data on the character of isolates in Romania.

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Invasive disease by Streptococcus pyogenes : Patients hospitalized for 6 years

Enfermedades infecciosas y microbiologia clinica (English ed ) ◽

10.1016/j.eimce.2018.04.007 ◽

2018 ◽

Vol 36 (6) ◽

pp. 352-356

Author(s):

Vanessa Arias-Constantí ◽

Victoria Trenchs-Sainz de la Maza ◽

Nuria Elvira Sanz-Marcos ◽

Carmina Guitart-Pardellans ◽

Amadeu Gené-Giralt ◽

...

Keyword(s):

Streptococcus Pyogenes ◽

Invasive Disease

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