Detection of invasive protein profile of <i>Streptococcus pyogenes</i> M1 isolates from pharyngitis patients

Hasegawa, Tadao; Okamoto, Akira; Kamimura, Takuya; Tatsuno, Ichiro; Hashikawa, Shinnosuke; Yabutani, Mitsutaka; Matsumoto, M.; Yamada, Keiko; Isaka, Masanori; Minami, Masaaki; Ohta, Michio

doi:10.1111/j.1600-0463.2009.02574.x

Cited by 24 publications

(42 citation statements)

References 49 publications

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“…The S. pyogenes strains used in this study were SF370 (Ferretti et al, 2001) and the 1529 clinical isolate from a Japanese patient with STSS. As far as CovS is concerned, comparison of the covS sequence with that of SF370 indicated that the mutation in 1529 is the same as the one previously reported [994(AAG), relative to the covS start site, amino acid change IAV] (Sumby et al, 2005;Hasegawa et al, 2010b).…”

Section: Methodssupporting

confidence: 69%

Analysis of two-component sensor proteins involved in the response to acid stimuli in Streptococcus pyogenes

et al. 2011

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The virulence of Streptococcus pyogenes depends on proteins that are produced by this bacterium. The production of virulence proteins depends on environmental factors, and twocomponent regulatory systems are considered to be involved in sensing these factors. One of the environmental factors is acid stimuli. We established knockout strains in all speculated twocomponent regulatory sensor proteins of the M1 clinical strain of S. pyogenes and examined their relevance to acid stimuli. The parental strain and its derived knockout strains were cultured in a medium adjusted to pH 7.6 or 6.0, and their growth in broth was compared. The spy1622 sensor knockout strain showed significant growth reduction compared with the parental strain in broth at pH 6.0, suggesting that the Spy1622 two-component sensor protein is involved in sensing acid stimuli. To further examine the role of the Spy1622 two-component sensor protein in virulence, blood bactericidal assays and mouse infection model experiments were performed. We found that the spy1622 knockout strain was less virulent than the parental strain, which suggests that the Spy1622 two-component sensor protein could play an important role in virulence. INTRODUCTIONStreptococcus pyogenes is a Gram-positive bacterium that infects the upper respiratory tract, for example the tonsils and pharynx, and causes serious post-infectious diseases such as rheumatic fever and glomerulonephritis. Furthermore, S. pyogenes causes even more serious human diseases such as streptococcal toxic shock syndrome (STSS), whose mortality rate is considerable (Cone et al., 1987;Cunningham, 2000). Because of the worldwide prevalence of STSS, a number of studies have been undertaken to identify relevant virulence factors (Hauser et al., 1991;Reichardt et al., 1992). These factors include M protein, streptococcal inhibitor of complement, streptococcal pyrogenic toxins, haemolysins, and several DNases (Cunningham, 2000).The production of virulence proteins depends on environmental factors such as pH. Bacterial growth and the host environment, such as that in phagocytic cells, can cause local and temporal pH changes, and bacteria can subsequently sense the pH change as a signal to modify their growth mode. In addition, bacteria can modulate their gene expression in response to changes in pH (Loughman & Caparon, 2006). Hence, pH is considered to play an important role in host colonization and infection by S. pyogenes.The regulation of virulence protein expression in S. pyogenes is mainly controlled by stand-alone response regulators and two-component regulatory systems (TCSs). Stand-alone transcriptional regulators have no identified sensory domain (Kreikemeyer et al., 2003). The three characterized stand-alone regulators include Mga, Rgg and RofA-like family members (McIver et al., 1995;Beckert et al., 2001;Chaussee et al., 1999;Lyon et al., 1998;Molinari et al., 2001;Podbielski et al., 1999). A TCS consists of a sensor protein and a regulatory protein.Thirteen TCSs have been identified in the available S. ...

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Section: Methodssupporting

confidence: 69%

Analysis of two-component sensor proteins involved in the response to acid stimuli in Streptococcus pyogenes

et al. 2011

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“…Streptococcal strains 1529, MDYK, and MDN were isolated from Japanese patients with STSS [21,22]. S. pyogenes (GAS) strain SF370, which is currently the most prevalent database reference isolate (accession number NC_002737), was provided by J. J. Ferretti [23,24].…”

Section: Methodsmentioning

confidence: 99%

Relevance of the two-component sensor protein CiaH to acid and oxidative stress responses in Streptococcus pyogenes

et al. 2014

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BackgroundThe production of virulence proteins depends on environmental factors, and two-component regulatory systems are involved in sensing these factors. We previously established knockout strains in all suspected two-component regulatory sensor proteins of the emm1 clinical strain of S. pyogenes and examined their relevance to acid stimuli in a natural atmosphere. In the present study, their relevance to acid stimuli was re-examined in an atmosphere containing 5% CO2.ResultsThe spy1236 (which is identical to ciaHpy) sensor knockout strain showed significant growth reduction compared with the parental strain in broth at pH 6.0, suggesting that the Spy1236 (CiaHpy) two-component sensor protein is involved in acid response of S. pyogenes. CiaH is also conserved in Streptococcus pneumoniae, and it has been reported that deletion of the gene for its cognate response regulator (ciaRpn) made the pneumococcal strains more sensitive to oxidative stress. In this report, we show that the spy1236 knockout mutant of S. pyogenes is more sensitive to oxidative stress than the parental strain.ConclusionsThese results suggest that the two-component sensor protein CiaH is involved in stress responses in S. pyogenes.

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“…Engleberg et al [15] showed that most covS mutations were frameshift or nonsense mutations in isolates from mice infected with the M1 strain. In contrast, all of the spontaneous changes in CovS detected in clinical M1 isolates [22] resulted from single amino acid substitutions. Thus, we were interested in why this difference occurred and we hypothesized that it was related to the use of animal-passaged isolates in the first study whereas the latter used clinical isolates.…”

Section: Introductionmentioning

confidence: 99%

Partial loss of CovS function in Streptococcus pyogenes causes severe invasive disease

et al. 2013

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BackgroundCovRS (or CsrRS) is a two-component regulatory system that regulates the production of multiple virulence factors in Streptococcus pyogenes. covS mutations are often found in isolates recovered from mice that have been experimentally infected with S. pyogenes and covS mutations enhance bacterial virulence in an invasive infection mouse model. In addition, covS mutations were detected more frequently in a panel of clinical isolates from severe invasive streptococcal infections than those from non-severe infections. Thus, covS mutations may be associated with the onset of severe invasive infections.ResultsKnown covS mutations were divided into two groups: (i) frameshift mutations that caused a deletion of functional regions and (ii) point mutations that caused single (or double) amino acid(s) substitutions. Frameshift mutations are frequent in mouse-passaged isolates, whereas point mutations are frequent in clinical isolates. The functions of CovS proteins with a single amino acid substitution in clinical isolates were estimated based on the streptococcal pyrogenic exotoxin B (SpeB) production and NAD+-glycohydrolase (NADase) activity, which are known to be regulated by the CovRS system. Point mutations partially, but not completely, impaired the function of the covS alleles. We also investigated some of the benefits that a partial loss of function in covS alleles with point mutations might confer on clinical isolates. We found that covS knockout mutants (ΔcovS strains) had an impaired growth ability in a normal atmosphere in Todd Hewitt broth compared with parental isolates having wild-type or point-mutated covS.ConclusionsThe loss of CovS proteins in S. pyogenes may confer greater virulence, but bacteria may also lose the ability to respond to certain external signals recognized by CovS. Therefore, point mutations that retain the function of CovS and confer hypervirulence may have natural selective advantages.

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Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients

Cited by 24 publications

References 49 publications

Analysis of two-component sensor proteins involved in the response to acid stimuli in Streptococcus pyogenes

Analysis of two-component sensor proteins involved in the response to acid stimuli in Streptococcus pyogenes

Relevance of the two-component sensor protein CiaH to acid and oxidative stress responses in Streptococcus pyogenes

Partial loss of CovS function in Streptococcus pyogenes causes severe invasive disease

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