scholarly journals Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of emm89 Streptococcus pyogenes

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Luchang Zhu ◽  
Randall J. Olsen ◽  
Waleed Nasser ◽  
Ivan de la Riva Morales ◽  
James M. Musser
Keyword(s):  
Hyaluronic Acid ◽  
Streptococcus Pyogenes ◽  
Molecular Mechanisms ◽  
Great Majority ◽  
Whole Genome Sequence ◽  
Phylogenetic Groups ◽  
Content Type ◽  
Genetic Features ◽  
Clade 1 ◽  
Hyaluronic Acid Capsule

ABSTRACTStrains ofemm89Streptococcus pyogeneshave become one of the major causes of invasive infections worldwide in the last 10 years. We recently sequenced the genome of 1,125emm89strains and identified three major phylogenetic groups, designated clade 1, clade 2, and the epidemic clade 3. Epidemic clade 3 strains, which now cause the great majority of infections, have two distinct genetic features compared to clade 1 and clade 2 strains. First, all clade 3 organisms have a variant 3ngapromoter region pattern, which is associated with increased production of secreted cytolytic toxins SPN (S. pyogenesNADase) and SLO (streptolysin O). Second, all clade 3 strains lack thehasABClocus mediating hyaluronic acid capsule synthesis, whereas this locus is intact in clade 1 and clade 2 strains. We constructed isogenic mutant strains that produce different levels of SPN and SLO toxins and capsule (none, low, or high). Here we report thatemm89strains with elevated toxin production are significantly more virulent than low-toxin producers. Importantly, we also show that capsule production is dispensable for virulence in strains that already produce high levels of SPN and SLO. Our results provide new understanding about the molecular mechanisms contributing to the rapid emergence and molecular pathogenesis of epidemic clade 3emm89S. pyogenes.IMPORTANCES. pyogenes(group A streptococcus [GAS]) causes pharyngitis (“strep throat”), necrotizing fasciitis, and other human infections. Serious infections caused byemm89S. pyogenesstrains have recently increased in frequency in many countries. Based on whole-genome sequence analysis of 1,125 strains recovered from patients on two continents, we discovered that a newemm89clone, termed clade 3, has two distinct genetic features compared to its predecessors: (i) absence of the genes encoding antiphagocytic hyaluronic acid capsule virulence factor and (ii) increased production of the secreted cytolytic toxins SPN and SLO.emm89S. pyogenesstrains with the clade 3 phenotype (absence of capsule and high expression of SPN and SLO) are highly virulent in mice. These findings provide new understanding of how new virulent clones emerge and cause severe infections worldwide. This newfound knowledge ofS. pyogenesvirulence can be used to help understand future epidemics and conduct new translational research.

scholarly journals The Emergence of Successful Streptococcus pyogenes Lineages through Convergent Pathways of Capsule Loss and Recombination Directing High Toxin Expression

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Claire E. Turner ◽  
Matthew T. G. Holden ◽  
Beth Blane ◽  
Carolyne Horner ◽  
Sharon J. Peacock ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Gene Transfer ◽  
Homologous Recombination ◽  
Streptococcus Pyogenes ◽  
High Expression ◽  
Data Set ◽  
Altered Expression ◽  
Content Type ◽  
Hyaluronic Acid Capsule ◽  
Inactivating Mutations

ABSTRACT Gene transfer and homologous recombination in Streptococcus pyogenes has the potential to trigger the emergence of pandemic lineages, as exemplified by lineages of emm1 and emm89 that emerged in the 1980s and 2000s, respectively. Although near-identical replacement gene transfer events in the nga (NADase) and slo (streptolysin O) loci conferring high expression of these toxins underpinned the success of these lineages, extension to other emm genotype lineages is unreported. The emergent emm89 lineage was characterized by five regions of homologous recombination additional to nga-slo, including complete loss of the hyaluronic acid capsule synthesis locus hasABC, a genetic trait replicated in two other leading emm types and recapitulated by other emm types by inactivating mutations. We hypothesized that other leading genotypes may have undergone similar recombination events. We analyzed a longitudinal data set of genomes from 344 clinical invasive disease isolates representative of locations across England, dating from 2001 to 2011, and an international collection of S. pyogenes genomes representing 54 different genotypes and found frequent evidence of recombination events at the nga-slo locus predicted to confer higher toxin genotype. We identified multiple associations between recombination at this locus and inactivating mutations within hasAB, suggesting convergent evolutionary pathways in successful genotypes. This included common genotypes emm28 and emm87. The combination of no or low capsule and high expression of nga and slo may underpin the success of many emergent S. pyogenes lineages of different genotypes, triggering new pandemics, and could change the way S. pyogenes causes disease. IMPORTANCE Streptococcus pyogenes is a genetically diverse pathogen, with over 200 different genotypes defined by emm typing, but only a minority of these genotypes are responsible for the majority of human infection in high-income countries. Two prevalent genotypes associated with disease rose to international dominance following recombination of a toxin locus that conferred increased expression. Here, we found that recombination of this locus and promoter has occurred in other diverse genotypes, events that may allow these genotypes to expand in the population. We identified an association between the loss of hyaluronic acid capsule synthesis and high toxin expression, which we propose may be associated with an adaptive advantage. As S. pyogenes pathogenesis depends both on capsule and toxin production, new variants with altered expression may result in abrupt changes in the molecular epidemiology of this pathogen in the human population over time.

scholarly journals Complete Genome Sequence of Escherichia coli O157:H7 Phage PhiG17

2019 ◽  
Vol 8 (3) ◽  
Author(s):  
Muyiwa A. Akindolire ◽  
Bukola R. Aremu ◽  
Collins N. Ateba
Keyword(s):  
Escherichia Coli ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Whole Genome Sequence ◽  
Escherichia Coli O157 ◽  
Content Type ◽  
North West ◽  
The North ◽  
Genetic Features

Here, we announce the complete genome sequence of bacteriophage PhiG17, which is virulent to Escherichia coli O157:H7 strains and was isolated from cattle feces in the North West province of South Africa. This report presents the major genetic features of the phage PhiG17 based on its whole-genome sequence.

scholarly journals Transcription of the Streptococcus pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated by Previously Unknown Upstream Elements

2014 ◽  
Vol 82 (12) ◽  
pp. 5293-5307 ◽  
Author(s):  
Marina Falaleeva ◽  
Oliwia W. Zurek ◽  
Robert L. Watkins ◽  
Robert W. Reed ◽  
Hadeel Ali ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Streptococcus Pyogenes ◽  
Regulatory Region ◽  
Regulatory System ◽  
Invasive Disease ◽  
Negative Regulator ◽  
Mobility Shift ◽  
Putative Promoter ◽  
Transcriptional Terminator ◽  
Content Type

ABSTRACTThe important human pathogenStreptococcus pyogenes(group AStreptococcus[GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that thehasABCoperon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an intrinsic transcriptional terminator that inefficiently terminates HasS, permitting read-through transcription ofhasABC, and a putative promoter which lies upstream of P2. Electrophoretic mobility shift assays, quantitative reverse transcription-PCR, and transcriptional reporter data identified CovR as a negative regulator of P2. We found that the P1 and P2 promoters are completely repressed by CovR, and capsule expression is regulated by the putative promoter upstream of P2. Deletion ofhasSor of the terminator eliminates CovR-binding sequences, relieving repression and increasing read-through,hasAtranscription, and capsule production. Sequence analysis of 44 GAS genomes revealed a high level of polymorphism in the HasS sequence region. Most of the HasS variations were located in the terminator sequences, suggesting that this region is under strong selective pressure. We discovered that the terminator deletion mutant is highly resistant to neutrophil-mediated killing and is significantly more virulent in a mouse model of GAS invasive disease than the wild-type strain. Together, these results are consistent with the naturally occurring mutations in this region modulating GAS virulence.

scholarly journals One More Disguise in the Stealth Behavior of Streptococcus pyogenes

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Vincent A. Fischetti ◽  
James B. Dale
Keyword(s):  
Hyaluronic Acid ◽  
Streptococcus Pyogenes ◽  
Treated Patient ◽  
Vantage Point ◽  
The Body ◽  
Eukaryotic Cells ◽  
Animal Kingdom ◽  
Human Joints ◽  
Hyaluronic Acid Capsule ◽  
Acid Lining

ABSTRACT The ability to hide in the animal kingdom is essential for survival; the same is true for bacteria . Streptococcus pyogenes is considered one of the more successful stealth bacteria in its production of a hyaluronic acid capsule that is chemically identical to the hyaluronic acid lining human joints. It has also acquired the capacity to enter eukaryotic cells to avoid the onslaught of the host’s immune defenses, as well as drugs. From this intracellular vantage point, it may remain dormant from days to weeks, only to cause disease again at a later time, perhaps causing a relapse in a drug-treated patient. We now learn that it is able to enter macrophages as well, enabling the Streptococcus to use this “Trojan horse” approach to be transported to distant sites in the body.

scholarly journals Whole-Genome Sequence of ablaOXA-48-Harboring Raoultella ornithinolytica Clinical Isolate from Lebanon

2016 ◽  
Vol 60 (4) ◽  
pp. 2548-2550 ◽  
Author(s):  
Charbel Al-Bayssari ◽  
Abiola Olumuyiwa Olaitan ◽  
Thongpan Leangapichart ◽  
Liliane Okdah ◽  
Fouad Dabboussi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Clinical Isolate ◽  
Genome Sequence ◽  
Resistance Genes ◽  
Molecular Mechanisms ◽  
Antibiotic Resistance Genes ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Genetic Organization

ABSTRACTWe analyzed the whole-genome sequence of ablaOXA-48-harboringRaoultella ornithinolyticaclinical isolate from a patient in Lebanon. The size of theRaoultella ornithinolyticaCMUL058 genome was 5,622,862 bp, with a G+C content of 55.7%. We deciphered all the molecular mechanisms of antibiotic resistance, and we compared our genome to other availableR. ornithinolyticagenomes in GenBank. The resistome consisted of 9 antibiotic resistance genes, including a plasmidicblaOXA-48gene whose genetic organization is also described.

scholarly journals T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 Streptococcus pyogenes

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Yi-Hsuan Chen ◽  
Shao-Hui Li ◽  
Yao-Cheng Yang ◽  
Shu-Hao Hsu ◽  
Victor Nizet ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Epithelial Cells ◽  
Streptococcus Pyogenes ◽  
Whole Blood ◽  
Human Pathogen ◽  
Human Whole Blood ◽  
Epidemiologic Surveillance ◽  
Group A ◽  
Hyaluronic Acid Capsule

ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is an important human pathogen causing a broad spectrum of diseases and associated with significant global morbidity and mortality. Almost all GAS isolates express a surface hyaluronic acid capsule, a virulence determinant that facilitates host colonization and impedes phagocyte killing. However, recent epidemiologic surveillance has reported a sustained increase in both mucosal and invasive infections caused by nonencapsulated GAS, which questions the indispensable role of hyaluronic acid capsule in GAS pathogenesis. In this study, we found that pilus of M4 GAS not only significantly promotes biofilm formation, adherence, and cytotoxicity to human upper respiratory tract epithelial cells and keratinocytes, but also promotes survival in human whole blood and increased virulence in murine models of invasive infection. T4 antigen, the pilus backbone protein of M4 GAS, binds haptoglobin, an abundant human acute-phase protein upregulated upon infection and inflammation, on the bacterial surface. Haptoglobin sequestration reduces the susceptibility of nonencapsulated M4 GAS to antimicrobial peptides released from activated neutrophils and platelets. Our results reveal a previously unappreciated virulence-promoting role of M4 GAS pili, in part mediated by co-opting the biology of haptoglobin to mitigate host antimicrobial defenses. IMPORTANCE Group A Streptococcus (GAS) is a strict human pathogen causing more than 700 million infections globally each year. The majority of the disease-causing GAS are encapsulated, which greatly guarantees survival and dissemination in the host. Emergence of the capsule-negative GAS, such as M4 GAS, in recent epidemiologic surveillance alarms the necessity to elucidate the virulence determinants of these pathogens. Here, we found that M4 pili play an important role in promoting M4 GAS adherence and cytotoxicity to human pharyngeal epithelial cells and keratinocytes. The same molecule also significantly enhanced M4 GAS survival and replication in human whole blood and experimental murine infection. T4 antigen, which composes the backbone of M4 pili, was able to sequester the very abundant serum protein haptoglobin to further confer M4 GAS resistance to antibacterial substances released by neutrophils and platelets.

scholarly journals Whole-Genome Sequence of a Plant Growth-Promoting Strain, Serratia marcescens BTL07, Isolated from the Rhizoplane of Capsicum annuum L.

2020 ◽  
Vol 9 (18) ◽  
Author(s):  
Sudipta Dutta ◽  
Amena Khatun ◽  
Dipali Rani Gupta ◽  
Musrat Zahan Surovy ◽  
M. Mahbubur Rahman ◽  
...  
Keyword(s):  
Plant Growth ◽  
Serratia Marcescens ◽  
Genome Sequence ◽  
Molecular Mechanisms ◽  
Sequence Data ◽  
Growth Promotion ◽  
Draft Genome ◽  
Plant Diseases ◽  
Whole Genome Sequence ◽  
Content Type

Serratia marcescens strain BTL07, which has the ability to promote growth and suppress plant diseases, was isolated from the rhizoplane of a chili plant. The draft genome sequence data of the strain will contribute to advancing our understanding of the molecular mechanisms underlying plant growth promotion and tolerance to different stresses.

scholarly journals The RNA-Binding Chaperone Hfq Is an Important Global Regulator of Gene Expression in Pasteurella multocida and Plays a Crucial Role in Production of a Number of Virulence Factors, Including Hyaluronic Acid Capsule

2016 ◽  
Vol 84 (5) ◽  
pp. 1361-1370 ◽  
Author(s):  
Marianne Mégroz ◽  
Oded Kleifeld ◽  
Amy Wright ◽  
David Powell ◽  
Paul Harrison ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Virulence Factors ◽  
Crucial Role ◽  
Pasteurella Multocida ◽  
Rna Binding ◽  
Content Type ◽  
Protein Levels ◽  
Filamentous Hemagglutinin ◽  
Proteomic Analyses ◽  
Hyaluronic Acid Capsule

The Gram-negative bacteriumPasteurella multocidais the causative agent of a number of economically important animal diseases, including avian fowl cholera. NumerousP. multocidavirulence factors have been identified, including capsule, lipopolysaccharide (LPS), and filamentous hemagglutinin, but little is known about how the expression of these virulence factors is regulated. Hfq is an RNA-binding protein that facilitates riboregulation via interaction with small noncoding RNA (sRNA) molecules and their mRNA targets. Here, we show that aP. multocidahfqmutant produces significantly less hyaluronic acid capsule during all growth phases and displays reducedin vivofitness. Transcriptional and proteomic analyses of thehfqmutant during mid-exponential-phase growth revealed altered transcript levels for 128 genes and altered protein levels for 78 proteins. Further proteomic analyses of thehfqmutant during the early exponential growth phase identified 106 proteins that were produced at altered levels. Both the transcript and protein levels for genes/proteins involved in capsule biosynthesis were reduced in thehfqmutant, as were the levels of the filamentous hemagglutinin protein PfhB2 and its secretion partner LspB2. In contrast, there were increased expression levels of three LPS biosynthesis genes, encoding proteins involved in phosphocholine and phosphoethanolamine addition to LPS, suggesting that these genes are negatively regulated by Hfq-dependent mechanisms. Taken together, these data provide the first evidence that Hfq plays a crucial role in regulating the global expression ofP. multocidagenes, including the regulation of keyP. multocidavirulence factors, capsule, LPS, and filamentous hemagglutinin.

scholarly journals Whole-Genome Sequence of the Bacteriophage-Sensitive Strain Campylobacter jejuni NCTC12662

2017 ◽  
Vol 5 (21) ◽  
Author(s):  
Yilmaz Emre Gencay ◽  
Martine C. H. Sørensen ◽  
Lone Brøndsted
Keyword(s):  
Campylobacter Jejuni ◽  
Genome Sequence ◽  
Molecular Mechanisms ◽  
Sensitive Strain ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Host Interactions

ABSTRACT Campylobacter jejuni NCTC12662 has been the choice bacteriophage isolation strain due to its susceptibility to C. jejuni bacteriophages. This trait makes it a good candidate for studying bacteriophage–host interactions. We report here the whole-genome sequence of NCTC12662, allowing future elucidation of the molecular mechanisms of phage–host interactions in C. jejuni.

scholarly journals Whole-Genome Sequence of Streptococcus pyogenes Strain 591, Belonging to the Genotype emm 49

2021 ◽  
Vol 10 (43) ◽  
Author(s):  
Nadja Patenge ◽  
Christian Rückert ◽  
Jana Bull ◽  
Kevin Strey ◽  
Joern Kalinowski ◽  
...  
Keyword(s):  
Clinical Isolate ◽  
Genome Sequence ◽  
Streptococcus Pyogenes ◽  
Complete Genome ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type

Streptococcus pyogenes strain 591 is a clinical isolate belonging to the genotype emm 49. It has been intensively studied for its pathogenicity traits. In this study, the complete genome of strain 591 was sequenced. It consists of a chromosome of 1,762,765 bp with a G+C content of 38.5%.

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