scholarly journals Gene fitness landscape of group A streptococcus during necrotizing myositis

2018 ◽  
Author(s):  
Luchang Zhu ◽  
Randall J. Olsen ◽  
Stephen B. Beres ◽  
Jesus M. Eraso ◽  
Matthew Ojeda Saavedra ◽  
...  
Keyword(s):  
Fitness Landscape ◽  
Group A Streptococcus ◽  
Insertion Site ◽  
Pcr Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Necrotizing Myositis ◽  
Genes Encoding ◽  
Isogenic Mutant Strain ◽  
Group A

ABSTRACTNecrotizing fasciitis and myositis are devastating infections characterized by high mortality. Group A streptococcus (GAS) is a common cause of these infections, but the molecular pathogenesis is poorly understood. We report a genome-wide analysis using serotype M1 and M28 strains that identified novel GAS genes contributing to necrotizing myositis in nonhuman primates (NHP), a clinically relevant model. Using transposon directed insertion-site sequencing (TraDIS) we identified 126 and 116 GAS genes required for infection by serotype M1 and M28 organisms, respectively. For both M1 and M28 strains, more than 25% of the GAS genes required for necrotizing myositis encode known or putative transporters. Thirteen GAS transporters contributed to both M1 and M28 strain fitness in NHP myositis, including putative importers for amino acids, carbohydrates, and vitamins, and exporters for toxins, quorum sensing peptides, and uncharacterized molecules. Targeted deletion of genes encoding five transporters confirmed that each isogenic mutant strain was significantly impaired in causing necrotizing myositis in NHPs. qRT-PCR analysis showed that these five genes are expressed in infected NHP and human skeletal muscle. Certain substrate-binding lipoproteins of these transporters, such as Spy0271 and Spy1728, were previously documented to be surface-exposed, suggesting that our findings have translational research implications.

scholarly journals Gene fitness landscape of group A streptococcus during necrotizing myositis

2019 ◽  
Vol 129 (2) ◽  
pp. 887-901 ◽  
Author(s):  
Luchang Zhu ◽  
Randall J. Olsen ◽  
Stephen B. Beres ◽  
Jesus M. Eraso ◽  
Matthew Ojeda Saavedra ◽  
...  
Keyword(s):  
Fitness Landscape ◽  
Group A Streptococcus ◽  
Necrotizing Myositis ◽  
Group A

scholarly journals A Genome-Wide Analysis of Small Regulatory RNAs in the Human Pathogen Group A Streptococcus

PLoS ONE ◽  
2009 ◽  
Vol 4 (11) ◽  
pp. e7668 ◽  
Author(s):  
Nataly Perez ◽  
Jeanette Treviño ◽  
Zhuyun Liu ◽  
Siu Chun Michael Ho ◽  
Paul Babitzke ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Human Pathogen ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Small Regulatory Rnas ◽  
Group A ◽  
Regulatory Rnas

scholarly journals Treponema denticola biofilm-induced expression of a bacteriophage, toxin–antitoxin systems and transposases

Microbiology ◽  
2010 ◽  
Vol 156 (3) ◽  
pp. 774-788 ◽  
Author(s):  
Helen L. Mitchell ◽  
Stuart G. Dashper ◽  
Deanne V. Catmull ◽  
Rita A. Paolini ◽  
Steven M. Cleal ◽  
...  
Keyword(s):  
Pcr Analysis ◽  
Treponema Denticola ◽  
Gene Products ◽  
Planktonic Cells ◽  
Biofilm Model ◽  
Genome Wide ◽  
A Genome ◽  
Phage Dna ◽  
Genes Encoding ◽  
Genetic Mobility

Treponema denticola is an oral spirochaete that has been strongly associated with chronic periodontitis. The bacterium exists as part of a dense biofilm (subgingival dental plaque) accreted to the tooth. To determine T. denticola gene products important for persistence as a biofilm we developed a continuous-culture biofilm model and conducted a genome-wide transcriptomic analysis of biofilm and planktonic cells. A total of 126 genes were differentially expressed with a fold change of 1.5 or greater. This analysis identified the upregulation of putative prophage genes in the T. denticola 35405 genome. Intact bacteriophage particles were isolated from T. denticola and circular phage DNA was detected by PCR analysis. This represents the first, to our knowledge, functional bacteriophage isolated from T. denticola, which we have designated φtd1. In biofilm cells there was also an upregulation of genes encoding several virulence factors, toxin–antitoxin systems and a family of putative transposases. Together, these data indicate that there is a higher potential for genetic mobility in T. denticola when growing as a biofilm and that these systems are important for the biofilm persistence and therefore virulence of this bacterium.

scholarly journals Genome‐wide analysis of in vivo CcpA binding with and without its key co‐factor HPr in the major human pathogen group A Streptococcus

2020 ◽  
Author(s):  
Sruti DebRoy ◽  
Victor Aliaga‐Tobar ◽  
Gabriel Galvez ◽  
Srishtee Arora ◽  
Xiaowen Liang ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Human Pathogen ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Group A

scholarly journals Regulation of Polysaccharide Utilization Contributes to the Persistence of Group A Streptococcus in the Oropharynx

2007 ◽  
Vol 75 (6) ◽  
pp. 2981-2990 ◽  
Author(s):  
Samuel A. Shelburne ◽  
Nnaja Okorafor ◽  
Izabela Sitkiewicz ◽  
Paul Sumby ◽  
David Keith ◽  
...  
Keyword(s):  
Parental Strain ◽  
Group A Streptococcus ◽  
Transcriptional Regulator ◽  
Human Saliva ◽  
Transcript Levels ◽  
Expression Of Genes ◽  
Rich Media ◽  
Genes Encoding ◽  
Group A ◽  
Mutant Derivative

ABSTRACT Group A Streptococcus (GAS) genes that encode proteins putatively involved in polysaccharide utilization show growth phase-dependent expression in human saliva. We sought to determine whether the putative polysaccharide transcriptional regulator MalR influences the expression of such genes and whether MalR helps GAS infect the oropharynx. Analysis of 32 strains of 17 distinct M protein serotypes revealed that MalR is highly conserved across GAS strains. malR transcripts were detectable in patients with GAS pharyngitis, and the levels increased significantly during growth in human saliva compared to the levels during growth in glucose-containing or nutrient-rich media. To determine if MalR influenced the expression of polysaccharide utilization genes, we compared the transcript levels of eight genes encoding putative polysaccharide utilization proteins in the parental serotype M1 strain MGAS5005 and its ΔmalR isogenic mutant derivative. The transcript levels of all eight genes were significantly increased in the ΔmalR strain compared to the parental strain, especially during growth in human saliva. Following experimental infection, the ΔmalR strain persistently colonized the oropharynx in significantly fewer mice than the parental strain colonized, and the numbers of ΔmalR strain CFU recovered were significantly lower than the numbers of the parental strain CFU recovered. These data led us to conclude that MalR influences the expression of genes putatively involved in polysaccharide utilization and that MalR contributes to the persistence of GAS in the oropharynx.

Abstract 5340: Cardiac Resynchronization Therapy Corrects Dyssynchrony-induced Regional Gene Expression Changes on a Genomic Level

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Andreas S Barth ◽  
Takeshi Aiba ◽  
Victoria Halperin ◽  
Deborah DiSilvestre ◽  
Chakir Khalid ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Resynchronization Therapy ◽  
Cardiac Resynchronization ◽  
Functional Improvement ◽  
Large Animal ◽  
Atrial Pacing ◽  
Resynchronization Therapy ◽  
Genome Wide ◽  
A Genome ◽  
Genes Encoding

Purpose: Cardiac Resynchronization Therapy (CRT) improves symptoms and reduces mortality in patients with heart failure (HF). To characterize the molecular processes associated with functional improvement in CRT, we used a genomic approach in a large animal HF model. Methods: After creation of a left bundle branch block (LBBB), dogs in the HF group were subjected to either rapid atrial pacing with 200 bpm for 6 weeks (dyssynchronous HF, DHF, n=10), or 3 weeks of atrial pacing followed by 3 weeks of biventricular stimulation at 200bpm (CRT, n=9). Control animals without LBBB were not paced (NF, n=11). After 6 weeks, RNA from anterior and lateral regions of the LV was hybridized onto canine 44K arrays. Statistical Analysis of Microarrays (SAM) was used for data analysis. Results: Echocardiographically, CRT led to a significant increase in stroke volume (+27%, p=0.03) which translated into a non-significant increase in EF (DHF 25±4%; CRT 31±3% (p=0.15); NF 67±3%). A multiclass analysis of NF, DHF and CRT animals identified 1050 differentially expressed transcripts between anterior and lateral walls with a false discovery rate of 5%. For all these transcripts, dyssynchrony-induced expression changes were reversed by CRT to levels of NF hearts. As a result, CRT samples clustered with NF rather than DHF samples. Of particular interest were genes encoding for signal transduction pathways and contractile processes. Conclusions: By using a whole genome approach, we demonstrate a profound effect of electrical activation on the regional cardiac transcriptome. This is the first study showing that dyssynchrony-induced gene expression changes can be corrected by CRT on a genome-wide level.

scholarly journals Genome-wide survey of sucrose non-fermenting 1-related protein kinase 2 in Rosaceae and expression analysis of PbrSnRK2 in response to ABA stress

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Guodong Chen ◽  
Jizhong Wang ◽  
Xin Qiao ◽  
Cong Jin ◽  
Weike Duan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Gene Family ◽  
Structural Characteristics ◽  
Purifying Selection ◽  
Related Protein ◽  
Rosaceae Species ◽  
Genome Wide ◽  
A Genome ◽  
Genes Encoding ◽  
Genome Wide Survey

Abstract Background The members of the sucrose non-fermenting 1-related protein kinase 2 (SnRK2) family are specific serine/threonine protein kinases in plants that play important roles in stress signal transduction and adaptation. Because of their positive regulatory roles in response to adverse conditions, the genes encoding thes proteins are considered potential candidates for breeding of plants for disease resistance and genetic improvement. However, there is far less information about this kinase family, and the function of these genes has not been explored in Rosaceae. Results A genome-wide survey and analysis of the genes encoding members of the SnRK2 family were performed in pear (Pyrus bretschneideri) and seven other Rosaceae species. A total of 71 SnRK2 genes were identified from the eight Rosaceae species and classified into three subgroups based on phylogenetic analysis and structural characteristics. Purifying selection played a crucial role in the evolution of SnRK2 genes, and whole-genome duplication and dispersed duplication were the primary forces underlying the characteristics of the SnRK2 gene family in Rosaceae. Transcriptome data and qRT-PCR assay results revealed that the distribution of PbrSnRK2s was very extensive, including across the roots, leaves, pollen, styles, and flowers, although most of them were mainly expressed in leaves. In addition, under stress conditions, the transcript levels of some of the genes were upregulated in leaves in response to ABA treatment. Conclusions This study provides useful information and a theoretical introduction for the study of the evolution, expression, and functions of the SnRK2 gene family in plants.

scholarly journals Group A Streptococcus AdcR Regulon Participates in Bacterial Defense against Host-Mediated Zinc Sequestration and Contributes to Virulence

2020 ◽  
Vol 88 (8) ◽  
Author(s):  
Nishanth Makthal ◽  
Hackwon Do ◽  
Brian M. Wendel ◽  
Randall J. Olsen ◽  
John D. Helmann ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Group A Streptococcus ◽  
Zn Deficiency ◽  
Direct Competition ◽  
Mutant Strains ◽  
Genes Encoding ◽  
Group A ◽  
Gas Interactions

ABSTRACT Colonization by pathogenic bacteria depends on their ability to overcome host nutritional defenses and acquire nutrients. The human pathogen group A streptococcus (GAS) encounters the host defense factor calprotectin (CP) during infection. CP inhibits GAS growth in vitro by imposing zinc (Zn) limitation. However, GAS counterstrategies to combat CP-mediated Zn limitation and the in vivo relevance of CP-GAS interactions to bacterial pathogenesis remain unknown. Here, we report that GAS upregulates the AdcR regulon in response to CP-mediated Zn limitation. The AdcR regulon includes genes encoding Zn import (adcABC), Zn sparing (rpsN.2), and Zn scavenging systems (adcAII, phtD, and phtY). Each gene in the AdcR regulon contributes to GAS Zn acquisition and CP resistance. The ΔadcC and ΔrpsN.2 mutant strains were the most susceptible to CP, whereas the ΔadcA, ΔadcAII, and ΔphtD mutant strains displayed less CP sensitivity during growth in vitro. However, the ΔphtY mutant strain did not display an increased CP sensitivity. The varied sensitivity of the mutant strains to CP-mediated Zn limitation suggests distinct roles for individual AdcR regulon genes in GAS Zn acquisition. GAS upregulates the AdcR regulon during necrotizing fasciitis infection in WT mice but not in S100a9−/− mice lacking CP. This suggests that CP induces Zn deficiency in the host. Finally, consistent with the in vitro results, several of the AdcR regulon genes are critical for GAS virulence in WT mice, whereas they are dispensable for virulence in S100a9−/− mice, indicating the direct competition for Zn between CP and proteins encoded by the GAS AdcR regulon during infection.

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