Identification of a Streptolysin S-Associated Gene Cluster and Its Role in the Pathogenesis of<i>Streptococcus iniae</i>Disease

Fuller, Jeffrey; Camus, Alvin C.; Duncan, Carla; Nizet, Victor; Bast, Darrin J.; Thune, Ronald L.; Low, Donald E.; Azavedo, Joyce C. S. de

doi:10.1128/iai.70.10.5730-5739.2002

Cited by 65 publications

(86 citation statements)

References 48 publications

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“…The other genes in the operon contribute to the maturation (sagB, sagC, and sagD) and secretion (sagG, sagH, and sagI) of SLS (22,23). The genetic structure of the sag operon is highly conserved in the pyogenic group species (25,26). Recently, the presence of sag operon homologues has been reported in other Gram-positive human pathogens: for example, Clostridium spp.…”

Section: Discussionmentioning

confidence: 99%

Novel Twin Streptolysin S-Like Peptides Encoded in the sag Operon Homologue of Beta-Hemolytic Streptococcus anginosus

Tabata

Nakano

Ohkura

et al. 2013

Journal of Bacteriology

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dStreptococcus anginosus is a member of the anginosus group streptococci, which form part of the normal human oral flora. In contrast to the pyogenic group streptococci, our knowledge of the virulence factors of the anginosus group streptococci, including S. anginosus, is not sufficient to allow a clear understanding of the basis of their pathogenicity. Generally, hemolysins are thought to be important virulence factors in streptococcal infections. In the present study, a sag operon homologue was shown to be responsible for beta-hemolysis in S. anginosus strains by random gene knockout. Interestingly, contrary to pyogenic group streptococci, beta-hemolytic S. anginosus was shown to have two tandem sagA homologues, encoding streptolysin S (SLS)-like peptides, in the sag operon homologue. Gene deletion and complementation experiments revealed that both genes were functional, and these SLS-like peptides were essential for beta-hemolysis in beta-hemolytic S. anginosus. Furthermore, the amino acid sequence of these SLS-like peptides differed from that of the typical SLS of S. pyogenes, especially in their propeptide domain, and an amino acid residue indicated to be important for the cytolytic activity of SLS in S. pyogenes was deleted in both S. anginosus homologues. These data suggest that SLS-like peptides encoded by two sagA homologues in beta-hemolytic S. anginosus may be potential virulence factors with a different structure essential for hemolytic activity and/or the maturation process compared to the typical SLS present in pyogenic group streptococci.

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Section: Discussionmentioning

confidence: 99%

Novel Twin Streptolysin S-Like Peptides Encoded in the sag Operon Homologue of Beta-Hemolytic Streptococcus anginosus

Tabata

Nakano

Ohkura

et al. 2013

Journal of Bacteriology

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“…The Nterminal domain (PatD1) shares weak similarity with adenylating enzymes such as acyl-CoA ligases, and with MccB, the adenylating enzyme responsible for the biosynthesis of the microcins C51 and C7 (42). The PatD C terminus (PatD2) is similar to YcaO-like conserved domains of unknown function but also to SagD from Streptococcus iniae, which may serve as a hydrolase (43). PatD2 shows similarity to TtufA, a protein involved in the synthesis of the ribosomally derived trifolitoxin (44).…”

Section: Correlation Of the Presence Of The Pat Gene Cluster With Patmentioning

confidence: 99%

“…since its discovery 50 years ago (48), yet its structure has not been elucidated. The presence of a McbC-like oxidase and a PatD2-like hydrolase (SagD) in the streptolysin S biosynthetic gene cluster (43) indicate that streptolysin S likely contains thiazole rings. Indeed, the predicted streptolysin S prepropeptide contains numerous cysteine residues that could be cyclized.…”

Section: Correlation Of the Presence Of The Pat Gene Cluster With Patmentioning

confidence: 99%

Patellamide A and C biosynthesis by a microcin-like pathway inProchloron didemni, the cyanobacterial symbiont ofLissoclinum patella

Schmidt

Nelson

Rasko

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

548

717

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Prochloron spp. are obligate cyanobacterial symbionts of many didemnid family ascidians. It has been proposed that the cyclic peptides of the patellamide class found in didemnid extracts are synthesized by Prochloron spp., but studies in which host and symbiont cells are separated and chemically analyzed to identify the biosynthetic source have yielded inconclusive results. As part of the Prochloron didemni sequencing project, we identified patellamide biosynthetic genes and confirmed their function by heterologous expression of the whole pathway in Escherichia coli. The primary sequence of patellamides A and C is encoded on a single ORF that resembles a precursor peptide. We propose that this prepatellamide is heterocyclized to form thiazole and oxazoline rings, and the peptide is cleaved to yield the two cyclic patellamides, A and C. This work represents the full sequencing and functional expression of a marine natural-product pathway from an obligate symbiont. In addition, a related cluster was identified in Trichodesmium erythraeum IMS101, an important bloom-forming cyanobacterium.heterocycle ͉ tunicate ͉ ascidian ͉ genome sequencing ͉ lantibiotic

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“…To better understand the molecular genetic basis of virulence in this versatile pathogen, we created a library of randomly generated transposon mutants that we screened for virulence attenuation in hybrid striped bass (HSB; Morone chrysops6Morone saxatilis) (Buchanan et al, 2005). The analysis and study of mutants from this library, along with candidate gene approaches, has previously served to elucidate virulence factors contributing to S. iniae pathogenicity in fish, including phosphoglucomutase (Buchanan et al, 2005), streptolysin S (Fuller et al, 2002;Locke et al, 2007a) and capsular polysaccharide (Barnes et al, 2003;Locke et al, 2007a;Lowe et al, 2007;Miller & Neely, 2005). In addition, recent whole-genome pyrosequencing of S. iniae strain K288 has uncovered an mga-like pathogenicity locus (Locke et al, 2008), which includes an M-like protein virulence factor similar to the fibrinogen-binding proteins discovered in S. iniae strains QMA0076 and QMA0131 (Baiano et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The novel polysaccharide deacetylase homologue Pdi contributes to virulence of the aquatic pathogen Streptococcus iniae

et al. 2010

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The aquatic zoonotic pathogen Streptococcus iniae represents a threat to the worldwide aquaculture industry and poses a risk to humans who handle raw fish. Because little is known about the mechanisms of S. iniae pathogenesis or virulence factors, we established a highthroughput system combining whole-genome pyrosequencing and transposon mutagenesis that allowed us to identify virulence proteins, including Pdi, the polysaccharide deacetylase of S. iniae, that we describe here. Using bioinformatics tools, we identified a highly conserved signature motif in Pdi that is also conserved in the peptidoglycan deacetylase PgdA protein family. A Dpdi mutant was attenuated for virulence in the hybrid striped bass model and for survival in whole fish blood. Moreover, Pdi was found to promote bacterial resistance to lysozyme killing and the ability to adhere to and invade epithelial cells. On the other hand, there was no difference in the autolytic potential, resistance to oxidative killing or resistance to cationic antimicrobial peptides between S. iniae wild-type and Dpdi. In conclusion, we have demonstrated that pdi is involved in S. iniae adherence and invasion, lysozyme resistance and survival in fish blood, and have shown that pdi plays a role in the pathogenesis of S. iniae. Identification of Pdi and other S. iniae virulence proteins is a necessary initial step towards the development of appropriate preventive and therapeutic measures against diseases and economic losses caused by this pathogen. INTRODUCTIONIn the past few decades, the pathogen Streptococcus iniae has emerged as a major hindrance to aquaculture operations worldwide (Agnew & Barnes, 2007), causing economic losses measured in hundreds of millions of dollars annually. In addition, S. iniae has established itself as a zoonotic risk, especially in areas of the world that preferentially prepare and consume raw fish (Lau et al., 2003). To date, at least 25 human cases of invasive streptococcal infection attributed to S. iniae have been confirmed in the USA, Canada, China and Taiwan, many of which were in immunocompromised patients (Agnew & Barnes, 2007;Sun et al., 2007;Weinstein et al., 1997); since there is currently no prospective epidemiological surveillance for human S. iniae infections, the true number may be much higher (Facklam et al., 2005;Lau et al., 2006).In spite of the economic and human health risks that S. iniae presents, a fully assembled genome sequence for this emerging pathogen is not yet available, and very little is known about its disease mechanisms. To better understand the molecular genetic basis of virulence in this versatile pathogen, we created a library of randomly generated transposon mutants that we screened for virulence Abbreviations: AMP, antimicrobial peptide; HSB, hybrid striped bass, i.p., intraperitoneal; PIA, polysaccharide intercellular adhesin, WT, wild-type.3These authors contributed equally to this work.The GenBank/EMBL/DDBJ accession number for the pdi sequence of Streptococcus iniae is FJ664396.Four supplementary f...

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Identification of a Streptolysin S-Associated Gene Cluster and Its Role in the Pathogenesis ofStreptococcus iniaeDisease

Cited by 65 publications

References 48 publications

Novel Twin Streptolysin S-Like Peptides Encoded in the sag Operon Homologue of Beta-Hemolytic Streptococcus anginosus

Novel Twin Streptolysin S-Like Peptides Encoded in the sag Operon Homologue of Beta-Hemolytic Streptococcus anginosus

Patellamide A and C biosynthesis by a microcin-like pathway inProchloron didemni, the cyanobacterial symbiont ofLissoclinum patella

The novel polysaccharide deacetylase homologue Pdi contributes to virulence of the aquatic pathogen Streptococcus iniae

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