Environmental Acidification Drives S. pyogenes Pilus Expression and Microcolony Formation on Epithelial Cells in a FCT-Dependent Manner

Manetti, Andrea G. O.; Köller, Thomas; Becherelli, Marco; Buccato, Scilla; Kreikemeyer, Bernd; Podbielski, Andreas; Grandi, Guido; Margarit, Immaculada

doi:10.1371/journal.pone.0013864

Cited by 50 publications

(67 citation statements)

References 57 publications

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“…Recently, site-directed mutagenesis suggested that LiaS may contribute to extracellular acidification and may be activated under acidic conditions, and this directly affected biofilm formation (44). Further, GAS pili contribute to biofilm formation, and, at least for a subset of FCT types, a lower environmental pH enhances pilus gene transcription (45). More studies are needed to further define the precise mechanism of pilus gene regulation by LiaFSR and the mechanism by which the liaS R135G carrier mutation alters pilus gene transcription.…”

Section: Fig 5 Elimination Of Pilus In Mgas10870 Liasmentioning

confidence: 99%

Increased Pilus Production Conferred by a Naturally Occurring Mutation Alters Host-Pathogen Interaction in Favor of Carriage in Streptococcus pyogenes

et al. 2017

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Studies of the human pathogen group A Streptococcus (GAS) define the carrier phenotype to be an increased ability to adhere to and persist on epithelial surfaces and a decreased ability to cause disease. We tested the hypothesis that a single amino acid change (Arg135Gly) in a highly conserved sensor kinase (LiaS) of a poorly defined GAS regulatory system contributes to a carrier phenotype through increased pilus production. When introduced into an emm serotype-matched invasive strain, the carrier allele (the gene encoding the LiaS protein with an arginine-toglycine change at position 135 [liaS R135G ]) recapitulated a carrier phenotype defined by an increased ability to adhere to mucosal surfaces and a decreased ability to cause disease. Gene transcript analyses revealed that the liaS mutation significantly altered transcription of the genes encoding pilus in the presence of bacitracin. Elimination of pilus production in the isogenic carrier mutant decreased its ability to colonize the mouse nasopharynx and to adhere to and be internalized by cultured human epithelial cells and restored the virulence phenotype in a mouse model of necrotizing fasciitis. We also observed significantly reduced survival of the isogenic carrier mutant compared to that of the parental invasive strain after exposure to human neutrophils. Elimination of pilus in the isogenic carrier mutant increased the level of survival after exposure to human neutrophils to that for the parental invasive strain. Together, our data demonstrate that the carrier mutation (liaS R135G ) affects pilus expression. Our data suggest new mechanisms of pilus gene regulation in GAS and that the invasiveness associated with pilus gene regulation in GAS differs from the enhanced invasiveness associated with increased pilus production in other bacterial pathogens.

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Section: Fig 5 Elimination Of Pilus In Mgas10870 Liasmentioning

confidence: 99%

Increased Pilus Production Conferred by a Naturally Occurring Mutation Alters Host-Pathogen Interaction in Favor of Carriage in Streptococcus pyogenes

et al. 2017

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“…Among the various serotype strains, serotype M6 strains produce high levels of biofilm in vitro, regardless of culture conditions (23,32). To evaluate whether FCT type 1 pili are necessary for biofilm formation, wild-type and mutant strains were grown in C medium, and the ability to form biofilm on polystyrene plates was assessed by crystal violet staining (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In fact, several GAS factors, including transcriptional regulators, have been reported to promote or attenuate biofilm formation (7,10,12,27,29,51); thus it is likely that such formation is a multifactorial event. However, our recent epidemiological studies clearly showed associations between several FCT types and the capability to form biofilms (23,32,43,44). …”

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confidence: 94%

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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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“…FCT type 9 isolates were poor biofilm producers, while FCT type 3 and 4 isolates were unequally and irregular biofilm producers. Manetti et al [44] demonstrated association between biofilm formation among FCT types 2, 3, 5, 6 and FCT subset 4 in acidic surroundings.…”

Section: Biofilmmentioning

confidence: 99%

Adherence and Biofilm Production of Streptococcus pyogenes

Šmitran¹,

Gajić²,

Božić³

et al. 2016

Microbial Biofilms - Importance and Applications

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Streptococcus pyogenes (group A streptococcus -GAS) can cause numerous human infections, varying from mild skin infections to life-threatening, e.g. necrotizing fasciitis. Adherence and biofilm production are important in streptoccocal pathogenesis. GAS adhesins are numerous and diverse, with the ability to bind to several different receptors at the same time, which leads to difficulties in their precise identification and classification. Biofilm production is one of the most probable explanation for therapeutic failure in the treatment of GAS infections. Most researchers agreed that biofilm formation is a trait of individual strains rather than a general serotype attribute. The aim of our study is to investigate differences in adherence to laminin and biofilm production between invasive and non-invasive isolates (NI) of GAS. In this study the correlation between adherence to laminin and invasiveness in GAS isolates is noticed. The strains isolated from GAS carriers and highly invasive (HI) GAS strains have excellent capacity for binding to laminin. When testing biofilm production, there was noticeable positive correlation between adherence and biofilm production among non-invasive isolates. Non-invasive isolates were stable biofilm productors. There was no correlation between adherence and biofilm production among invasive isolates. Invasive isolates were also unstable biofilm productors.

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Environmental Acidification Drives S. pyogenes Pilus Expression and Microcolony Formation on Epithelial Cells in a FCT-Dependent Manner

Cited by 50 publications

References 57 publications

Increased Pilus Production Conferred by a Naturally Occurring Mutation Alters Host-Pathogen Interaction in Favor of Carriage in Streptococcus pyogenes

Increased Pilus Production Conferred by a Naturally Occurring Mutation Alters Host-Pathogen Interaction in Favor of Carriage in Streptococcus pyogenes

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

Adherence and Biofilm Production of Streptococcus pyogenes

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