scholarly journals Phosphotransferase System Uptake and Metabolism of the β-Glucoside Salicin Impact Group A Streptococcal Bloodstream Survival and Soft Tissue Infection

2020 ◽  
Vol 88 (10) ◽  
Author(s):  
Rezia Era Braza ◽  
Aliyah B. Silver ◽  
Ganesh S. Sundar ◽  
Sarah E. Davis ◽  
Afrooz Razi ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Infection ◽  
Tissue Infection ◽  
Phosphotransferase System ◽  
Content Type ◽  
Growth And Survival ◽  
Successful Infection ◽  
Group A ◽  
The Individual

ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]), a major human-specific pathogen, relies on efficient nutrient acquisition for successful infection within its host. The phosphotransferase system (PTS) couples the import of carbohydrates with their phosphorylation prior to metabolism and has been linked to GAS pathogenesis. In a screen of an insertional mutant library of all 14 annotated PTS permease (EIIC) genes in MGAS5005, the annotated β-glucoside PTS transporter (bglP) was found to be crucial for GAS growth and survival in human blood and was validated in another M1T1 GAS strain, 5448. In 5448, bglP was shown to be in an operon with a putative phospho-β-glucosidase (bglB) downstream and a predicted antiterminator (licT) upstream. Using defined nonpolar mutants of the β-glucoside permease (bglP) and β-glucosidase enzyme (bglB) in 5448, we showed that bglB, not bglP, was important for growth in blood. Furthermore, transcription of the licT-blgPB operon was found to be repressed by glucose and induced by the β-glucoside salicin as the sole carbon source. Investigation of the individual bglP and bglB mutants determined that they influence in vitro growth in the β-glucoside salicin; however, only bglP was necessary for growth in other non-β-glucoside PTS sugars, such as fructose and mannose. Additionally, loss of BglP and BglB suggests that they are important for the regulation of virulence-related genes that control biofilm formation, streptolysin S (SLS)-mediated hemolysis, and localized ulcerative lesion progression during subcutaneous infections in mice. Thus, our results indicate that the β-glucoside PTS transports salicin and its metabolism can differentially influence GAS pathophysiology during soft tissue infection.

scholarly journals The Phosphoenolpyruvate Phosphotransferase System in Group A Streptococcus Acts To Reduce Streptolysin S Activity and Lesion Severity during Soft Tissue Infection

2013 ◽  
Vol 82 (3) ◽  
pp. 1192-1204 ◽  
Author(s):  
Kanika Gera ◽  
Tuquynh Le ◽  
Rebecca Jamin ◽  
Zehava Eichenbaum ◽  
Kevin S. McIver
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Infection ◽  
Group A Streptococcus ◽  
Carbon Sources ◽  
Tissue Infection ◽  
Growth Defect ◽  
Wild Type ◽  
Phosphotransferase System ◽  
Streptolysin S ◽  
Group A

ABSTRACTObtaining essential nutrients, such as carbohydrates, is an important process for bacterial pathogens to successfully colonize host tissues. The phosphoenolpyruvate phosphotransferase system (PTS) is the primary mechanism by which bacteria transport sugars and sense the carbon state of the cell. The group A streptococcus (GAS) is a fastidious microorganism that has adapted to a variety of niches in the human body to elicit a wide array of diseases. A ΔptsImutant (enzyme I [EI] deficient) generated in three different strains of M1T1 GAS was unable to grow on multiple carbon sources (PTS and non-PTS). Complementation withptsIexpressed under its native promoter in single copy was able to rescue the growth defect of the mutant. In a mouse model of GAS soft tissue infection, all ΔptsImutants exhibited a significantly larger and more severe ulcerative lesion than mice infected with the wild type. Increased transcript levels ofsagAand streptolysin S (SLS) activity during exponential-phase growth was observed. We hypothesized that early onset of SLS activity would correlate with the severity of the lesions induced by the ΔptsImutant. In fact, infection of mice with a ΔptsI sagBdouble mutant resulted in a lesion comparable to that of either the wild type or asagBmutant alone. Therefore, a functional PTS is not required for subcutaneous skin infection in mice; however, it does play a role in coordinating virulence factor expression and disease progression.

scholarly journals Genome-wide discovery of novel M1T1 group A streptococcal determinants important for fitness and virulence during soft-tissue infection

2017 ◽  
Vol 13 (8) ◽  
pp. e1006584 ◽  
Author(s):  
Yoann Le Breton ◽  
Ashton T. Belew ◽  
Jeffrey A. Freiberg ◽  
Ganesh S. Sundar ◽  
Emrul Islam ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Infection ◽  
Tissue Infection ◽  
Genome Wide ◽  
Group A

scholarly journals A case of infection caused by the basidiomycete Phellinus undulatus

2011 ◽  
Vol 60 (2) ◽  
pp. 256-258 ◽  
Author(s):  
Deborah Williamson ◽  
Sushil Pandey ◽  
Susan Taylor ◽  
Karen Rogers ◽  
Louanne Storey ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Molecular Analysis ◽  
Soft Tissue Infection ◽  
Human Infection ◽  
Morphological Features ◽  
Tissue Infection

We present a case of soft tissue infection caused by the basidiomycete Phellinus undulatus. To our knowledge, this is the first reported case of human infection caused by this fungus. Definitive identification was only possible through molecular analysis as the isolate failed to produce any distinct morphological features in vitro.

scholarly journals CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection

2019 ◽  
Author(s):  
Leah K. Horstemeyer ◽  
JooYoun Park ◽  
Elizabeth A. Swanson ◽  
Mary Catherine Beard ◽  
Emily M. McCabe ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Soft Tissue ◽  
Soft Tissue Infection ◽  
Bone Infection ◽  
Tissue Infection ◽  
Fluorescent Imaging ◽  
Alginate Hydrogel ◽  
Antibiotic Resistant

AbstractOsteomyelitis, or bone infection, is often induced by antibiotic resistant Staphylococcus aureus strains of bacteria. Although debridement and long-term administration of antibiotics are the gold standard for osteomyelitis treatment, the increase in prevalence of antibiotic resistant bacterial strains limits the ability of clinicians to effectively treat infection. Bacteriophages (phages), viruses that effectively lyse bacteria, have gained recent attention for their high specificity, non-toxicity, and the low likelihood of resistance development by pathogens. Previously, we have shown that CRISPR-Cas9 genomic editing techniques could be utilized to expand bacteriophage host range and enhance bactericidal activity through modification of the tail fiber protein, as well as improve safety with removal of major virulence genes. In a dermal infection study, these CRISPR-Cas9 phages reduced bacterial load relative to unmodified phage. Thus, we hypothesized this bacteriophage would be effective to mitigate infection from a biofilm forming S. aureus strain in vitro and in vivo. In vitro, qualitative fluorescent imaging demonstrated superiority of phage to conventional vancomycin and fosfomycin antibiotics against S. aureus biofilm. Quantitative antibiofilm effects increased over time for fosfomycin, phage, and fosfomycin-phage (dual) therapeutics delivered via alginate hydrogel. We developed an in vivo rat model of osteomyelitis and soft tissue infection that was reproducible and challenging and enabled longitudinal monitoring of infection progression. Using this model, phage (with and without fosfomycin) delivered via alginate hydrogel were successful in reducing soft tissue infection but not bone infection, based on bacteriological, histological, and scanning electron microscopy analyses. Notably, the efficacy of phage at mitigating soft tissue infection was equal to that of high dose fosfomycin. Future research may utilize this model as a platform for evaluation of therapeutic type and dose, and alternate delivery vehicles for osteomyelitis mitigation.

scholarly journals Draft Genome Sequence of Blood-Origin Streptococcus canis Strain FU149, Isolated from a Dog with Necrotizing Soft Tissue Infection

2020 ◽  
Vol 9 (35) ◽  
Author(s):  
Yasuto Fukushima ◽  
Yoshiteru Murata ◽  
Yukie Katayama ◽  
Yuzo Tsuyuki ◽  
Haruno Yoshida ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Genome Sequence ◽  
Soft Tissue Infection ◽  
Reference Genome ◽  
Draft Genome ◽  
Tissue Infection ◽  
Draft Genome Sequence ◽  
Necrotizing Soft Tissue Infection ◽  
Content Type ◽  
Streptococcus Canis

ABSTRACT The draft genome sequence of the blood-origin Streptococcus canis strain FU149, isolated from a dog with a necrotizing soft tissue infection in Japan, is reported. The genome size was 2.108 Mbp, with a G+C content of 39.5%. Sequences unmapped to the reference genome sequence of NCTC 12191T (GenBank accession number LR134293) were characterized.

scholarly journals Rat Pneumonia and Soft-Tissue Infection Models for the Study of Acinetobacter baumannii Biology

2008 ◽  
Vol 76 (8) ◽  
pp. 3577-3586 ◽  
Author(s):  
Thomas A. Russo ◽  
Janet M. Beanan ◽  
Ruth Olson ◽  
Ulrike MacDonald ◽  
Nicole R. Luke ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Acinetobacter Baumannii ◽  
Soft Tissue Infection ◽  
Drug Targets ◽  
Tissue Infection ◽  
Clinical Isolates ◽  
Infection Model ◽  
Infection Models

ABSTRACT Acinetobacter baumannii is a bacterial pathogen of increasing medical importance. Little is known about its mechanisms of pathogenesis, and safe reliable agents with predictable activity against A. baumannii are presently nonexistent. The availability of relevant animal infection models will facilitate the study of Acinetobacter biology. In this report we tested the hypothesis that the rat pneumonia and soft-tissue infection models that our laboratory had previously used for studies of extraintestinal pathogenic Escherichia coli were clinically relevant for A. baumannii. Advantages of these models over previously described models were that the animals were not rendered neutropenic and they did not receive porcine mucin with bacterial challenge. Using the A. baumannii model pathogen 307-0294 as the challenge pathogen, the pneumonia model demonstrated all of the features of infection that are critical for a clinically relevant model: namely, bacterial growth/clearance, an ensuing host inflammatory response, acute lung injury, and, following progressive bacterial proliferation, death due to respiratory failure. We were also able to demonstrate growth of 307-0294 in the soft-tissue infection model. Next we tested the hypothesis that the soft-tissue infection model could be used to discriminate between the inherent differences in virulence of various A. baumannii clinical isolates. The ability of A. baumannii to grow and/or be cleared in this model was dependent on the challenge strain. We also hypothesized that complement is an important host factor in protecting against A. baumannii infection in vivo. In support of this hypothesis was the observation that the serum sensitivity of various A. baumannii clinical isolates in vitro roughly paralleled their growth/clearance in the soft-tissue infection model in vivo. Lastly we hypothesized that the soft-tissue infection model would serve as an efficient screening mechanism for identifying gene essentiality for drug discovery. Random mutants of 307-0294 were initially screened for lack of growth in human ascites in vitro. Selected mutants were subsequently used for challenge in the soft-tissue infection model to determine if the disrupted gene was essential for growth in vivo. Using this approach, we have been able to successfully identify a number of genes essential for the growth of 307-0294 in vivo. In summary, these models are clinically relevant and can be used to study the innate virulence of various Acinetobacter clinical isolates and to assess potential virulence factors, vaccine candidates, and drug targets in vivo and can be used for pharmacokinetic and chemotherapeutic investigations.

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