Pathogenetic Mechanisms in Gram-Positive Shock: Studies on the Ability of Streptococcus pyogenes to Induce Nitric Oxide In Vitro

Author(s):  
P. Mills ◽  
T. Evans ◽  
J. Cohen
2009 ◽  
Vol 53 (11) ◽  
pp. 4762-4771 ◽  
Author(s):  
Francis F. Arhin ◽  
Deborah C. Draghi ◽  
Chris M. Pillar ◽  
Thomas R. Parr ◽  
Gregory Moeck ◽  
...  

ABSTRACT Oritavancin activity was tested against 15,764 gram-positive isolates collected from 246 hospital centers in 25 countries between 2005 and 2008. Organisms were Staphylococcus aureus (n = 9,075), coagulase-negative staphylococci (n = 1,664), Enterococcus faecalis (n = 1,738), Enterococcus faecium (n = 819), Streptococcus pyogenes (n = 959), Streptococcus agalactiae (n = 415), group C, G, and F streptococci (n = 84), and Streptococcus pneumoniae (n = 1,010). Among the evaluated staphylococci, 56.7% were resistant to oxacillin. The vancomycin resistance rate among enterococci was 21.2%. Penicillin-resistant and -intermediate rates were 14.7% and 21.4%, respectively, among S. pneumoniae isolates. Among nonpneumococcal streptococci, 18.5% were nonsusceptible to erythromycin. Oritavancin showed substantial in vitro activity against all organisms tested, regardless of resistance profile. The maximum oritavancin MIC against all staphylococci tested (n = 10,739) was 4 μg/ml; the MIC90 against S. aureus was 0.12 μg/ml. Against E. faecalis and E. faecium, oritavancin MIC90s were 0.06 and 0.12, respectively. Oritavancin was active against glycopeptide-resistant enterococci, including VanA strains (n = 486), with MIC90s of 0.25 and 1 μg/ml against VanA E. faecium and E. faecalis, respectively. Oritavancin showed potent activity against streptococci (n = 2,468); MIC90s for the different streptococcal species were between 0.008 and 1 μg/ml. These data are consistent with previous studies with respect to resistance rates of gram-positive isolates and demonstrate the spectrum and in vitro activity of oritavancin against a wide variety of contemporary gram-positive pathogens, regardless of resistance to currently used drugs. The data provide a foundation for interpreting oritavancin activity and potential changes in susceptibility over time once oritavancin enters into clinical use.


2000 ◽  
Vol 44 (6) ◽  
pp. 1749-1753 ◽  
Author(s):  
Wendy J. Munckhof ◽  
Glenn Borlace ◽  
John D. Turnidge

ABSTRACT We investigated the in vitro postantibiotic effects (PAEs) of the ketolides telithromycin (HMR 3647) and HMR 3004 and analyzed the results using the sigmoid E max model. Mean maximum telithromycin PAEs against erythromycin A-susceptible strains of Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae were 3.7, 8.9, and 9.7 h, respectively, while maximum PAEs for erythromycin A-resistant strains were much shorter. Mean maximum HMR 3004 PAEs were 3.2 to 4.4 h for all species.


2013 ◽  
Vol 82 (1) ◽  
pp. 233-242 ◽  
Author(s):  
Zachary T. Cusumano ◽  
Michael E. Watson ◽  
Michael G. Caparon

ABSTRACTA bacterium's ability to acquire nutrients from its host during infection is an essential component of pathogenesis. For the Gram-positive pathogenStreptococcus pyogenes, catabolism of the amino acid arginine via the arginine deiminase (ADI) pathway supplements energy production and provides protection against acid stressin vitro. Its expression is enhanced in murine models of infection, suggesting an important rolein vivo. To gain insight into the function of the ADI pathway in pathogenesis, the virulence of mutants defective in each of its enzymes was examined. Mutants unable to use arginine (ΔArcA) or citrulline (ΔArcB) were attenuated for carriage in a murine model of asymptomatic mucosal colonization. However, in a murine model of inflammatory infection of cutaneous tissue, the ΔArcA mutant was attenuated but the ΔArcB mutant was hyperattenuated, revealing an unexpected tissue-specific role for citrulline metabolism in pathogenesis. When mice defective for the arginine-dependent production of nitric oxide (iNOS−/−) were infected with the ΔArcA mutant, cutaneous virulence was rescued, demonstrating that the ability ofS. pyogenesto utilize arginine was dispensable in the absence of nitric oxide-mediated innate immunity. This work demonstrates the importance of arginine and citrulline catabolism and suggests a novel mechanism of virulence by whichS. pyogenesuses its metabolism to modulate innate immunity through depletion of an essential host nutrient.


2006 ◽  
Vol 50 (6) ◽  
pp. 2255-2257 ◽  
Author(s):  
Paul A. Wickman ◽  
Jennifer A. Black ◽  
Ellen Smith Moland ◽  
Kenneth S. Thomson

ABSTRACT The in vitro activity of the novel quinolone DX-619 was compared to those of currently available quinolones against U.S. clinical isolates of Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp., Streptococcus pyogenes, and Streptococcus pneumoniae. DX-619 was the most potent quinolone overall, indicating possible utility as an anti-gram-positive quinolone.


2008 ◽  
Vol 76 (6) ◽  
pp. 2612-2619 ◽  
Author(s):  
Jason W. Rosch ◽  
Luis Alberto Vega ◽  
John M. Beyer ◽  
Ada Lin ◽  
Michael G. Caparon

ABSTRACT The signal recognition particle (SRP) pathway is a universally conserved pathway for targeting polypeptides for secretion via the cotranslational pathway. In particular, the SRP pathway is thought to be the main mechanism for targeting polypeptides in gram-positive bacteria, including a number of important human pathogens. Though widely considered to be an essential cellular component, recent advances have indicated this pathway may be dispensable in gram-positive bacteria of the genus Streptococcus under in vitro conditions. However, its importance for the pathogenesis of streptococcal disease is unknown. In this study, we investigated the importance of the SRP pathway for virulence factor secretion in the human pathogen Streptococcus pyogenes. While the SRP pathway was not found to be essential for viability in vitro, SRP mutants demonstrated a medium-specific growth defect that could be rescued by the addition of glucose. We also observed that a distinct subset of virulence factors were dependent upon the SRP pathway for secretion, whereas others were completely independent of this pathway. Significantly, deletion of the SRP pathway resulted in mutants that were highly attenuated in both a zebrafish model of necrotic myositis and a murine subcutaneous ulcer model, highlighting the importance of this pathway in vivo. These studies emphasize the importance of the SRP pathway for the in vivo survival and pathogenesis of S. pyogenes.


Author(s):  
C. Thiemermann ◽  
M. Kengatharan ◽  
S. J. De Kimpe

1996 ◽  
Vol 119 (7) ◽  
pp. 1411-1421 ◽  
Author(s):  
Ken. M. Kengatharan ◽  
Sjef J. Kimpe ◽  
Christoph Thiemermann

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