scholarly journals Genetic heterogeneity of the Spy1336/R28 – Spy1337 Virulence Axis in Streptococcus pyogenes and Effect on Gene Transcript Levels and Pathogenesis

2019 ◽  
Author(s):  
Jesus M. Eraso ◽  
Priyanka Kachroo ◽  
Randall J. Olsen ◽  
Stephen B. Beres ◽  
Luchang Zhu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Streptococcus Pyogenes ◽  
Natural Populations ◽  
Size Variation ◽  
Homopolymeric Tract ◽  
Transcript Levels ◽  
Isogenic Mutant ◽  
Necrotizing Myositis ◽  
Mutant Strains ◽  
Invasive Infections

ABSTRACTStreptococcus pyogenes is a strict human pathogen responsible for more than 700 million infections annually worldwide. Strains of serotype M28 S. pyogenes are typically among the five more abundant types causing invasive infections and pharyngitis in adults and children. Type M28 strains also have an unusual propensity to cause puerperal sepsis and neonatal disease. We recently discovered that a one-nucleotide indel in an intergenic homopolymeric tract located between genes Spy1336/R28 and Spy1337 altered virulence in a mouse model of infection. In the present study, we analyzed size variation in this homopolymeric tract and determined the extent of heterogeneity in the number of tandemly-repeated 79-amino acid domains in the coding region of Spy1336/R28 in large samples of strains recovered from humans with invasive infections. Both repeat sequence elements are highly polymorphic in natural populations of M28 strains. Variation in the homopolymeric tract results in (i) changes in transcript levels of Spy1336/R28 and Spy1337 in vitro, (ii) differences in virulence in a mouse model of necrotizing myositis, and (iii) global transcriptome changes as shown by RNAseq analysis of isogenic mutant strains. Variation in the number of tandem repeats in the coding sequence of Spy1336/R28 is responsible for size variation of R28 protein in natural populations. Isogenic mutant strains in which genes encoding R28 or transcriptional regulator Spy1337 are inactivated are significantly less virulent in a nonhuman primate model of necrotizing myositis. Our findings provide impetus for additional studies addressing the role of R28 and Spy1337 variation in pathogen-host interactions.

scholarly journals Independent evolution towards larger body size in the distinctive Faroe Island mice

2021 ◽  
Author(s):  
Ricardo Wilches ◽  
William H Beluch ◽  
Ellen McConnell ◽  
Diethard Tautz ◽  
Yingguang Frank Chan
Keyword(s):  
Body Size ◽  
Meta Analysis ◽  
Small Body ◽  
Laboratory Mouse ◽  
Large Body ◽  
Natural Populations ◽  
Size Variation ◽  
Phenotypic Traits ◽  
Island Population ◽  
Multiple Loci

Abstract Most phenotypic traits in nature involve the collective action of many genes. Traits that evolve repeatedly are particularly useful for understanding how selection may act on changing trait values. In mice, large body size has evolved repeatedly on islands and under artificial selection in the laboratory. Identifying the loci and genes involved in this process may shed light on the evolution of complex, polygenic traits. Here, we have mapped the genetic basis of body size variation by making a genetic cross between mice from the Faroe Islands, which are among the largest and most distinctive natural populations of mice in the world, and a laboratory mouse strain selected for small body size, SM/J. Using this F2 intercross of 841 animals, we have identified 111 loci controlling various aspects of body size, weight and growth hormone levels. By comparing against other studies, including the use of a joint meta-analysis, we found that the loci involved in the evolution of large size in the Faroese mice were largely independent from those of a different island population or other laboratory strains. We hypothesize that colonization bottleneck, historical hybridization, or the redundancy between multiple loci have resulted in the Faroese mice achieving an outwardly similar phenotype through a distinct evolutionary path.

scholarly journals A New Rapid and Cost-Effective Method for Detection of Phages, ICEs and Virulence Factors Encoded by Streptococcus pyogenes

2011 ◽  
Vol 60 (3) ◽  
pp. 187-201 ◽  
Author(s):  
ANNA L. BOREK ◽  
JOANNA WILEMSKA ◽  
RADOSŁAW IZDEBSKI ◽  
WALERIA HRYNIEWICZ ◽  
IZABELA SITKIEWICZ
Keyword(s):  
Virulence Factors ◽  
Streptococcus Pyogenes ◽  
Group A Streptococcus ◽  
Cost Effective ◽  
Cost Effective Method ◽  
Effective System ◽  
Genes Encoding ◽  
Invasive Infections ◽  
Integration Sites ◽  
Severity Of The Disease

Streptococcus pyogenes (group A Streptococcus, GAS) is a human pathogen that causes diseases of various intensity, from mild strep throat to life threatening invasive infections and postinfectional sequelae. S. pyogenes encodes multiple, often phage encoded, virulence factors and their presence is related to severity of the disease. Acquisition of mobile genetic elements, carrying virulence factors, as phages or ICEs (integrative and cojugative elements) has been shown previously to promote selection of virulent clones. We designed the system of eight low volume multi- and one singleplex PCR reactions to detect genes encoding twenty virulence factors (spd3, sdc, sdaB, sdaD, speB, spyCEP, scpA, mac, sic, speL, K, M, C, I, A, H, G, J, smeZ and ssa) and twenty one phage and ICE integration sites described so far for S. pyogenes. Classification of strains based on the phage and virulence factors absence or presence, correlates with PFGE MLST and emm typing results. We developed a novel, fast and cost effective system that can be used to detect GAS virulence factors. Moreover, this system may become an alternative and effective system to differentiate between GAS strains.

scholarly journals Genetic heterogeneity of the Spy1336/R28—Spy1337 virulence axis in Streptococcus pyogenes and effect on gene transcript levels and pathogenesis

PLoS ONE ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. e0229064
Author(s):  
Jesus M. Eraso ◽  
Priyanka Kachroo ◽  
Randall J. Olsen ◽  
Stephen B. Beres ◽  
Luchang Zhu ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Genetic Heterogeneity ◽  
Gene Transcript ◽  
Transcript Levels

scholarly journals Distribution of emm type and antibiotic susceptibility of group A streptococci causing invasive and noninvasive disease

2008 ◽  
Vol 57 (11) ◽  
pp. 1383-1388 ◽  
Author(s):  
Takeaki Wajima ◽  
Somay Y. Murayama ◽  
Katsuhiko Sunaoshi ◽  
Eiichi Nakayama ◽  
Keisuke Sunakawa ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Macrolide Antibiotic ◽  
Group A Streptococcus ◽  
Acute Otitis Media ◽  
Toxic Shock ◽  
Medical Institutions ◽  
Invasive Infections ◽  
Group A ◽  
Resistant Strains ◽  
Emm Type

To determine the prevalence of macrolide antibiotic and levofloxacin resistance in infections with Streptococcus pyogenes (group A streptococcus or GAS), strains were collected from 45 medical institutions in various parts of Japan between October 2003 and September 2006. Four hundred and eighty-two strains from patients with GAS infections were characterized genetically. Strains were classified into four groups according to the type of infection: invasive infections (n=74) including sepsis, cellulitis and toxic-shock-like syndrome; acute otitis media (AOM; n=23); abscess (n=53); and pharyngotonsillitis (n=332). Among all strains, 32 emm types were identified; emm1 was significantly more common in invasive infections (39.2 %) and AOM (43.5 %) than in abscesses (3.8 %) or pharyngotonsillitis (10.2 %). emm12 and emm4 each accounted for 23.5 % of pharyngotonsillitis cases. Susceptibility of GAS strains to eight β-lactam agents was excellent, with MICs of 0.0005–0.063 μg ml−1. Macrolide-resistant strains accounted for 16.2 % of all strains, while the percentages of strains possessing the resistance genes erm(A), erm(B) and mef(A) were 2.5 %, 6.2 % and 7.5 %, respectively. Although no strains with high resistance to levofloxacin were found, strains with an MIC of 2–4 μg ml−1 (17.4 %) had amino acid substitutions at either Ser-79 or Asp-83 in ParC. These levofloxacin-intermediately resistant strains included 16 emm types, but macrolide-resistant strains were more likely than others to represent certain emm types.

scholarly journals Sex‐dependent and sex‐independent regulatory systems of size variation in natural populations

2019 ◽  
Vol 15 (11) ◽  
Author(s):  
Hirokazu Okada ◽  
Ryohei Yagi ◽  
Vincent Gardeux ◽  
Bart Deplancke ◽  
Ernst Hafen
Keyword(s):  
Natural Populations ◽  
Size Variation ◽  
Regulatory Systems

scholarly journals Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

2019 ◽  
Vol 216 (7) ◽  
pp. 1615-1629 ◽  
Author(s):  
Andreas Naegeli ◽  
Eleni Bratanis ◽  
Christofer Karlsson ◽  
Oonagh Shannon ◽  
Raja Kalluru ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Infection ◽  
Invasive Infections ◽  
Life Threatening ◽  
Group A ◽  
Specific Igg

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.

Effects of density and food limitation on size variation and mortality of larval Hexagenia rigida (Ephemeroptera: Ephemeridae)

1992 ◽  
Vol 70 (9) ◽  
pp. 1824-1832 ◽  
Author(s):  
Elizabeth C. Hanes ◽  
Jan J. H. Ciborowski
Keyword(s):  
Food Limitation ◽  
Larval Growth ◽  
Natural Populations ◽  
Size Variation ◽  
Food Level ◽  
Larval Size ◽  
Detroit River ◽  
Frequency Distributions ◽  
Exogenous Factors ◽  
Growth Differences

Natural populations of the burrowing mayfly belonging to the genus Hexagenia are characterized by unusually broad size-frequency distributions. Environmental features are often invoked to explain among-populations growth differences. We used a 4 × 4 factorial design to investigate differences in mean larval size and mortality of Hexagenia reared at different densities and food levels over four time intervals (30, 60, 90, and 120 d) in the laboratory. Larvae were hatched from eggs collected from imagoes at the Detroit River near Windsor, Ontario. Although neither density nor food limitation influenced larval growth at either 30 or 60 d growth, the number of days required for eggs to hatch did significantly influence larval growth at this time. At 30 d growth, larvae that hatched after 6 d incubation were significantly smaller than larvae that required an additional day to hatch (7 d). At both 30 and 60 d, larvae that hatched after 6 d incubation had lower mortality than larvae that hatched after 7 d. At 90 and 120 d growth, density and food significantly influenced larval size and mortality. Larvae reared at low density and with a high food level attained the largest size. Mortality increased under stressed conditions (high density and (or) low food level). Since endogenous features (day of hatch) can be important early in larval development (at 30 or 60 d), such features may contribute to the outcome of competitive events that occur later in development (at 90 or 120 d), when exogenous factors (density and food) become significant.

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