Assembly Mechanism of FCT Region Type 1 Pili in Serotype M6 Streptococcus pyogenes

Nakata, Masao; Kimura, Keiji; Sumitomo, Tomoko; Wada, Satoshi; Sugauchi, Akinari; Oiki, Eiji; Higashino, Miharu; Kreikemeyer, Bernd; Podbielski, Andreas; Okahashi, Nobuo; Hamada, Shigeyuki; Isoda, Ryutaro; Terao, Yutaka; Kawabata, Shigetada

doi:10.1074/jbc.m111.239780

Cited by 34 publications

(63 citation statements)

References 46 publications

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“…An in-frame speB deletion mutant, its complemented strain, and sagA-speB double mutant were constructed using pSET4s, as previously reported (11,17). Primers speBkoF1 (5Ј-GCGGATCCTGTTTAATCGAAATGTTTT-TTGAATGC-3Ј), speBkoR1 (5Ј-ACTTTGGTAACCGTTGA-AGCCCATTTTTTTTATACCTCTTTC-3Ј), speBkoF2 (5Ј-GAAAGAGGTATAAAAAAAATGGGCTTCAACGGTTAC-CAAAGT-3Ј), and speBkoR2 (5Ј-AACTGCAGGTCTTAAA-GGATGTACCGTATTGG-3Ј) were used for deletion of speB gene.…”

Section: Methodsmentioning

confidence: 99%

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation

Sumitomo

Nakata

Higashino

et al. 2013

Journal of Biological Chemistry

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Background: Group A Streptococcus (GAS) translocates across the host epithelial barrier. Results: Streptococcal pyrogenic exotoxin B (SpeB) directly cleaves junctional proteins. Conclusion:The proteolytic efficacy of SpeB allows GAS to translocate across the epithelial barrier. Significance: SpeB-mediated dysfunction of the epithelial barrier may have important implications for not only bacterial invasion but also dissemination of other virulence factors throughout intercellular spaces.

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Section: Methodsmentioning

confidence: 99%

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation

Sumitomo

Nakata

Higashino

et al. 2013

Journal of Biological Chemistry

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“…Additionally, this class B sortase also mediates the attachment of the minor pilin proteins, including the adhesin Cpa (Spy0125), which attaches to the tip of the pilus, and the basal pilin Spy0130, which acts as a linker protein for attachment to the cell wall (122,123). Sortase A is responsible for linking the pilus structure to the cell wall (124). The pilus biosynthesis and sortase genes are grouped together as a pathogenicity island located in the FCT region of the GAS genome, which encodes fibronectin binding proteins, collagen binding proteins, and T antigens (pilus subunit genes) (125).…”

Section: Adherence Of Gasmentioning

confidence: 99%

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

et al. 2014

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SUMMARY Streptococcus pyogenes , also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority.

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“…Therefore, it can be assumed that specific molecules responsible for the phenotype could be present in FCT type 1 strains. Serotype M6 GAS produces FCT type 1 pili, which consist of the backbone pilus protein T6 and the ancillary protein FctX (5,34,38,50). These are primarily assembled by a transpeptidase, SrtB, and anchored to the cell wall by the housekeeping sortase SrtA (33,38).…”

mentioning

confidence: 99%

“…Serotype M6 GAS produces FCT type 1 pili, which consist of the backbone pilus protein T6 and the ancillary protein FctX (5,34,38,50). These are primarily assembled by a transpeptidase, SrtB, and anchored to the cell wall by the housekeeping sortase SrtA (33,38). When the amino acid sequence of T6 was compared with that of backbone proteins from other types, T6 was found to show less than a 30% identity with proteins from FCT types 5, 6, and 9 and have no remarkable homology with sequences of backbone proteins from FCT types 2, 3, and 4 (15).…”

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confidence: 99%

Involvement of T6 Pili in Biofilm Formation by Serotype M6 Streptococcus pyogenes

et al. 2012

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The group A streptococcus (GAS) Streptococcus pyogenes is known to cause self-limiting purulent infections in humans. The role of GAS pili in host cell adhesion and biofilm formation is likely fundamental in early colonization. Pilus genes are found in the FCT (fibronectin-binding protein, collagen-binding protein, and trypsin-resistant antigen) genomic region, which has been classified into nine subtypes based on the diversity of gene content and nucleotide sequence. Several epidemiological studies have indicated that FCT type 1 strains, including serotype M6, produce large amounts of monospecies biofilm in vitro. We examined the direct involvement of pili in biofilm formation by serotype M6 clinical isolates. In the majority of tested strains, deletion of the tee6 gene encoding pilus shaft protein T6 compromised the ability to form biofilm on an abiotic surface. Deletion of the fctX and srtB genes, which encode pilus ancillary protein and class C pilus-associated sortase, respectively, also decreased biofilm formation by a representative strain. Unexpectedly, these mutant strains showed increased bacterial aggregation compared with that of the wild-type strain. When the entire FCT type 1 pilus region was ectopically expressed in serotype M1 strain SF370, biofilm formation was promoted and autoaggregation was inhibited. These findings indicate that assembled FCT type 1 pili contribute to biofilm formation and also function as attenuators of bacterial aggregation. Taken together, our results show the potential role of FCT type 1 pili in the pathogenesis of GAS infections. Bacterial biofilms are organized communities of cell aggregates that are embedded in a matrix of extracellular polymeric substances (9, 13). Biofilm formation is beneficial to bacteria in resistance to the activity of antimicrobial compounds and in persistence against host immune defenses (19). Hence, while many pathogenic bacteria form biofilms, they cause or exacerbate a variety of chronic or recurrent diseases, such as specific forms of recurrent tonsillitis, urinary tract infections, otitis media, and chronic rhino-sinusitis. In addition, biofilm-forming bacteria have a pathogenic role in cystic fibrosis-related lung infections and periodontitis as well as in implant material-related infections.Streptococcus pyogenes (group A streptococci [GAS]) is a human pathogen responsible for a wide variety of diseases ranging from self-limiting purulent infections, such as pharyngitis, tonsillitis, and impetigo, to severe necrotizing fasciitis and autoimmune diseases, including acute rheumatic fever and glomerulonephritis (11). To successfully cause such diverse diseases, firm adherence to epithelial cell surfaces and biofilm formation may be required for colonization in anatomical sites and subsequent disease progression. Indeed, recent studies have reported that GAS produced biofilms in in vitro and in vivo infection models (1,2,7,8,28,31,48,49). Among the many bacterial factors involved in GAS biofilm formation and host cell adherence, pili are pre...

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Assembly Mechanism of FCT Region Type 1 Pili in Serotype M6 Streptococcus pyogenes

Cited by 34 publications

References 46 publications

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

Involvement of T6 Pili in Biofilm Formation by Serotype M6 Streptococcus pyogenes

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