Sequence Variation in Group A<i>Streptococcus</i>Pili and Association of Pilus Backbone Types with Lancefield T Serotypes

Falugi, Fabiana; Zingaretti, Chiara; Pinto, Vittoria; Mariani, Massimo A.; Amodeo, Laura; Manetti, Andrea G. O.; Capo, Sabrina; Musser, James M.; Orefici, Graziella; Margarit, Immaculada; Telford, John L.; Grandi, Guido; Mora, Marirosa

doi:10.1086/593176

Cited by 111 publications

(159 citation statements)

References 26 publications

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“…Recent studies have demonstrated that the homologue of Spy0125 (called Cpa) in a serotype M3 S. pyogenes strain is localized at the tip of pili (37). There is considerable diversity among the loci (known as FCT regions) encompassing pilus gene clusters in different strains of S. pyogenes, and the FCT-3 region of M3 S. pyogenes differs from the FCT-1 region of the M1 strain SF370 studied here (9,21). Nevertheless, by using LC-MS/MS analysis and the spy0128K 161 A mutant, Spy0125 was shown to be joined to the pilus shaft through an intermolecular isopeptide bond linking its C-terminal Thr 723 to the ε-amino group of Lys 161 in Spy0128.…”

Section: Discussionmentioning

confidence: 78%

Roles of Minor Pilin Subunits Spy0125 and Spy0130 in the Serotype M1 Streptococcus pyogenes Strain SF370

Smith¹,

Pointon²,

Abbot³

et al. 2010

J Bacteriol

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Adhesive pili on the surface of the serotype M1 Streptococcus pyogenes strain SF370 are composed of a major backbone subunit (Spy0128) and two minor subunits (Spy0125 and Spy0130), joined covalently by a pilin polymerase (Spy0129). Previous studies using recombinant proteins showed that both minor subunits bind to human pharyngeal (Detroit) cells (A. G. Manetti et al., Mol. Microbiol. 64:968-983, 2007), suggesting both may act as pilus-presented adhesins. While confirming these binding properties, studies described here indicate that Spy0125 is the pilus-presented adhesin and that Spy0130 has a distinct role as a wall linker. Pili were localized predominantly to cell wall fractions of the wild-type S. pyogenes parent strain and a spy0125 deletion mutant. In contrast, they were found almost exclusively in culture supernatants in both spy0130 and srtA deletion mutants, indicating that the housekeeping sortase (SrtA) attaches pili to the cell wall by using Spy0130 as a linker protein. Adhesion assays with antisera specific for individual subunits showed that only anti-rSpy0125 serum inhibited adhesion of wild-type S. pyogenes to human keratinocytes and tonsil epithelium to a significant extent. Spy0125 was localized to the tip of pili, based on a combination of mutant analysis and liquid chromatography-tandem mass spectrometry analysis of purified pili. Assays comparing parent and mutant strains confirmed its role as the adhesin. Unexpectedly, apparent spontaneous cleavage of a labile, proline-rich (8 of 14 residues) sequence separating the N-terminal ϳ1/3 and C-terminal ϳ2/3 of Spy0125 leads to loss of the N-terminal region, but analysis of internal spy0125 deletion mutants confirmed that this has no significant effect on adhesion.

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Section: Discussionmentioning

confidence: 78%

Roles of Minor Pilin Subunits Spy0125 and Spy0130 in the Serotype M1 Streptococcus pyogenes Strain SF370

Smith¹,

Pointon²,

Abbot³

et al. 2010

J Bacteriol

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“…3D). The FCT locus is conserved in GAS strains of M-types 3, 5, 18, and 49 (FCT-3), but it shows variable gene content and poor sequence homology with FCT regions from other strains, such as M-type 1 GAS representing FCT-2 (15,46). srtC2 regulation was detectable in M-type 3 strain 003Sm, because our microarrays carry probes for the highly homologous srtC2 from M-type 18 GAS (spyM18_0129) (60), whereas regulation of the pilus structural genes was not detectable, since the microarrays contained probes specific to M-type 1 GAS.…”

Section: Resultsmentioning

confidence: 99%

Peroxide Stimulon and Role of PerR in Group A Streptococcus

et al. 2011

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We have characterized group A Streptococcus (GAS) genome-wide responses to hydrogen peroxide and assessed the role of the peroxide response regulator (PerR) in GAS under oxidative stress. Comparison of transcriptome changes elicited by peroxide in wild-type bacteria with those in a perR deletion mutant showed that 76 out of 237 peroxide-regulated genes are PerR dependent. Unlike the PerR-mediated upregulation of peroxidases and other peroxide stress defense mechanisms previously reported in Gram-positive species, PerR-dependent genes in GAS were almost exclusively downregulated and encoded proteins involved in purine and deoxyribonucleotide biosynthesis, heme uptake, and amino acid/peptide transport, but they also included a strongly activated putative transcriptional regulator (SPy1198). Of the 161 PerR-independent loci, repressed genes (86 of 161) encoded proteins with functions similar to those coordinated by PerR, in contrast to upregulated loci that encoded proteins that function in DNA damage repair, cofactor metabolism, reactive oxygen species detoxification, pilus biosynthesis, and hypothetical proteins. Complementation of the perR deletion mutant with wild-type PerR restored PerR-dependent regulation, whereas complementation with either one of two PerR variants carrying single mutations in two predicted metal-binding sites did not rescue the mutant phenotype. Metal content analyses of the recombinant wild type and respective PerR mutants, in addition to regulation studies in metal-supplemented and iron-depleted media, showed binding of zinc and iron by PerR and an iron requirement for optimal responses to peroxide. Our findings reveal a novel physiological contribution of PerR in coordinating DNA and protein metabolic functions in peroxide and identify GAS adaptive responses that may serve to enhance oxidative stress resistance and virulence in the host.

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“…The genes encoding pili of the pathogenic streptococci are found in discrete loci, termed PI. To date, three PI have been identified for S. agalactiae (512), two have been identified for S. pneumoniae (23), and nine have been identified for S. pyogenes (157), with the latter occurring within the Fn-binding, collagen-binding, T-antigen (FCT) region that forms part of the Lancefield T-serotyping system. While the exact composition varies, each PI comprises genes that encode LPxTz family proteins, which are linked to cell wall peptidoglycan precursors via sortase cleavage between T and z (see below).…”

Section: Pilimentioning

confidence: 99%

StreptococcusAdherence and Colonization

Nobbs

Lamont

Jenkinson

2009

Microbiol Mol Biol Rev

552

569

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SUMMARY Streptococci readily colonize mucosal tissues in the nasopharynx; the respiratory, gastrointestinal, and genitourinary tracts; and the skin. Each ecological niche presents a series of challenges to successful colonization with which streptococci have to contend. Some species exist in equilibrium with their host, neither stimulating nor submitting to immune defenses mounted against them. Most are either opportunistic or true pathogens responsible for diseases such as pharyngitis, tooth decay, necrotizing fasciitis, infective endocarditis, and meningitis. Part of the success of streptococci as colonizers is attributable to the spectrum of proteins expressed on their surfaces. Adhesins enable interactions with salivary, serum, and extracellular matrix components; host cells; and other microbes. This is the essential first step to colonization, the development of complex communities, and possible invasion of host tissues. The majority of streptococcal adhesins are anchored to the cell wall via a C-terminal LPxTz motif. Other proteins may be surface anchored through N-terminal lipid modifications, while the mechanism of cell wall associations for others remains unclear. Collectively, these surface-bound proteins provide Streptococcus species with a “coat of many colors,” enabling multiple intimate contacts and interplays between the bacterial cell and the host. In vitro and in vivo studies have demonstrated direct roles for many streptococcal adhesins as colonization or virulence factors, making them attractive targets for therapeutic and preventive strategies against streptococcal infections. There is, therefore, much focus on applying increasingly advanced molecular techniques to determine the precise structures and functions of these proteins, and their regulatory pathways, so that more targeted approaches can be developed.

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Sequence Variation in Group AStreptococcusPili and Association of Pilus Backbone Types with Lancefield T Serotypes

Cited by 111 publications

References 26 publications

Roles of Minor Pilin Subunits Spy0125 and Spy0130 in the Serotype M1 Streptococcus pyogenes Strain SF370

Roles of Minor Pilin Subunits Spy0125 and Spy0130 in the Serotype M1 Streptococcus pyogenes Strain SF370

Peroxide Stimulon and Role of PerR in Group A Streptococcus

StreptococcusAdherence and Colonization

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