Regulation of sagA, siaA and scpC by SilCR, a putative signaling peptide of Streptococcus pyogenes.

SilCR, a 17 amino acid putative signaling peptide, was proposed to modulate gene expression in Streptococcus pyogenes. We showed that SilCR added exogenously to an M1 serotype strain lacking the sil locus upregulates the in vitro expression of sagA, siaA, and scpC, genes associated with S. pyogenes pathogenesis.

The two-component system sivS/R regulates virulence in Streptococcus iniae.

Streptococcus iniae causes invasive disease and death in fish, and to a lesser extent, sporadic cases of soft-tissue infections in humans. A two-component system termed sivS/R, which regulates capsule expression, was previously identified and characterized. In this study, it is shown that a sivS/R deletion-insertion mutant, termed 9117Deltasiv, causes transient bacteremia and reduced virulence compared with the parent strain when tested in a murine model of bacteremic infection.

Antipneumococcal activity of ertapenem compared with gatifloxacin in a temperature-sensitive murine model of acute pneumonia.

Fluoroquinolone-resistance among pneumococci is low; however the number of isolates with a single ParC mutation has increased. Consequently, more potent agents are needed to minimize resistance selection. We investigated the efficacy of ertapenem versus gatifloxacin in a temperature-sensitive mouse model of pneumonia caused by a wildtype Streptococcus pneumoniae strain (A66) and an isogenic mutant with a ParC mutation (R222).

Role for sagA and siaA in quorum sensing and iron regulation in Streptococcus pyogenes.

Streptococcus pyogenes is a ubiquitous and versatile pathogen that causes a variety of infections with a wide range of severity. The versatility of this organism is due in part to its capacity to regulate virulence gene expression in response to the many environments that it encounters during an infection. We analyzed the expression of two potential virulence factors, sagA and siaA (also referred to as pel and htsA, respectively), in response to conditions of varying cell densities and iron concentrations.

Capsule expression regulated by a two-component signal transduction system in Streptococcus iniae.

Streptococcus iniae causes disease in fish and humans and the presence of capsule is associated with virulence. Tn917 transposon mutagenesis was performed to identify capsule-associated genes and a mutant was isolated, with an insertion in a genetic locus encoding a two-component signal transduction system (TCS), which we termed sivS/R. sivS and sivR encode a 506-amino-acid (aa) putative histidine kinase and a 223-aa putative response regulator, respectively.

Short-course therapy of gemifloxacin effective against pneumococcal pneumonia in mice.

Standard 7-14 day (d) courses of antimicrobial therapy for community-acquired pneumonia (CAP) are thought to have contributed to the emergence of resistant pneumoccoci. Consequently, short-course fluoroquinolone regimens have been proposed to minimize resistance. To test this, we examined 2-day versus 5-day regimens of gemifloxacin and levofloxacin for treatment of pneumonia in a murine model.

Relative potential for selection of quinolone-resistance-determining-region mutations in Streptococcus pneumoniae by gemifloxacin, gatifloxacin and moxifloxacin.

Serial passage of a clinical isolate of Streptococcus pneumoniae, in the presence of moxifloxacin, gatifloxacin or gemifloxacin, gave rise to resistant isolates. Non-susceptibility as defined by Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) breakpoints arose on Days 10, 11, and 12 with gatifloxacin, gemifloxacin, and moxifloxacin respectively. Moxifloxacin and gatifloxacin selected for a single step quinolone-resistant-determining-region (QRDR) mutation in DNA gyrase (GyrA) on Day 4 and 7 respectively, whereas gemifloxacin selected simultaneously for multi-step mutations in gyrase and topoisomerase IV (ParC) on Day 17 and activated a non-reserpine inhibited efflux mechanism by Day 4.

Identification of group A Streptococcus antigenic determinants upregulated in vivo.

Group A Streptococcus (GAS) causes a range of diseases in humans, from mild noninvasive infections to severe invasive infections. The molecular basis for the varying severity of disease remains unclear. We identified genes expressed during invasive disease using in vivo-induced antigen technology (IVIAT), applied for the first time in a gram-positive organism.

Prevalence and characterization of invasive isolates of Streptococcus pyogenes with reduced susceptibility to fluoroquinolones.

Fluoroquinolone susceptibility testing was performed on invasive group A streptococcus isolates from 1992-1993 and 2003 from Ontario, Canada. None were nonsusceptible to levofloxacin. Two of 153 (1.

Novel murine model of pneumococcal pneumonia: use of temperature as a measure of disease severity to compare the efficacies of moxifloxacin and levofloxacin.

Surface temperature measured by an infrared temperature-scanning thermometer was used to evaluate disease severity and predict imminent death in a murine model of pneumococcal pneumonia. We showed that a decrease in temperature was associated with increasing severity of disease and concomitant histological changes and also that a temperature of 30 degrees C or less was a predictor of death. Furthermore, viable bacterial counts in the lungs of mice euthanized at a temperature of < or = 30 degrees C were not significantly different from those seen in the lungs of mice allowed to die without intervention.

Type II topoisomerase mutations in Bacillus anthracis associated with high-level fluoroquinolone resistance.

Objectives: To identify and characterize the mechanisms of high-level fluoroquinolone resistance in two strains of Bacillus anthracis following serial passage in increasing concentrations of fluoroquinolones.

Methods: Fluoroquinolone-resistant isolates of the Sterne and Russian Anthrax Vaccine STi strains were obtained following serial passage in the presence of increasing concentrations of four different fluoroquinolones. The quinolone-resistance-determining regions of the type II topoisomerase genes from the resistant strains were amplified by PCR and characterized by DNA sequence analysis.

Modulation of bacterial growth by tumor necrosis factor-alpha in vitro and in vivo.

Tumor necrosis factor-alpha (TNF-alpha) plays an important role in innate immunity. Recent in vitro studies have shown that TNF-alpha may also serve as a growth factor for some bacteria. We examined the physiologic relevance of this phenomenon both in vitro and in vivo.

Antimicrobial susceptibility breakpoints and first-step parC mutations in Streptococcus pneumoniae: redefining fluoroquinolone resistance.

Clinical antimicrobial susceptibility breakpoints are used to predict the clinical outcome of antimicrobial treatment. In contrast, microbiologic breakpoints are used to identify isolates that may be categorized as susceptible when applying clinical breakpoints but harbor resistance mechanisms that result in their reduced susceptibility to the agent being tested. Currently, the National Committee for Clinical Laboratory Standards (NCCLS) guidelines utilize clinical breakpoints to characterize the activity of the fluoroquinolones against Streptococcus pneumoniae.

Emergence of macrolide resistance in throat culture isolates of group a streptococci in Ontario, Canada, in 2001.

Of 500 group A streptococci isolated from pharyngeal swabs, 72 (14.4%) were macrolide resistant, compared to 2.1% in 1997.

Identification of a streptolysin S-associated gene cluster and its role in the pathogenesis of Streptococcus iniae disease.

Streptococcus iniae causes meningoencephalitis and death in cultured fish species and soft-tissue infection in humans. We recently reported that S. iniae is responsible for local tissue necrosis and bacteremia in a murine subcutaneous infection model.

Activities of new fluoroquinolones, ketolides, and other antimicrobials against blood culture isolates of viridans group streptococci from across Canada, 2000.

The rates of nonsusceptibility to penicillin, erythromycin, and clindamycin of 191 blood culture isolates of viridans group streptococci collected from across Canada in 2000 were 36, 42, and 10%, respectively. Although 8% of the strains were resistant to ciprofloxacin (MIC >or= 4 microg/ml), the MICs of gemifloxacin, BMS 284756, telithromycin, and ABT 773 at which 90% of the strains were inhibited were 0.06, 0.

Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in Canada during 2000.

A total of 2,245 clinical isolates of Streptococcus pneumoniae were collected from 63 microbiology laboratories from across Canada during 2000 and characterized at a central laboratory. Of these isolates, 12.4% were not susceptible to penicillin (penicillin MIC, >or=0.

Activity of BMS-284756, a novel des-fluoro(6) quinolone, against Staphylococcus aureus, including contributions of mutations to quinolone resistance.

The in vitro activity of BMS-284756 against 602 Staphylococcus aureus isolates, including 152 that were both methicillin and ciprofloxacin resistant (MIC > or = 4 microg/ml), was determined. For ciprofloxacin-susceptible and nonsusceptible isolates, the MICs at which 50% of organisms were inhibited were 0.015 and 2 microg/ml and the MICs at which 90% of organisms were inhibited were 0.

Streptolysin S and necrotising infections produced by group G streptococcus.

Background: We encountered three patients with severe necrotising soft tissue infections due to beta-haemolytic group G streptococcus. Due to strong clinical similarities with invasive infections produced by group A streptococcus, we investigated a potential link of shared beta-haemolytic phenotype to disease pathogenesis.

Methods: Hybridisation, DNA sequencing, targeted mutagenesis, and complementation studies were used to establish the genetic basis for group G streptococcus beta-haemolytic activity.

Prevalence and mechanisms of macrolide resistance in invasive and noninvasive group B streptococcus isolates from Ontario, Canada.

Macrolide resistance has been demonstrated in group B streptococcus (GBS), but there is limited information regarding mechanisms of resistance and their prevalence. We determined these in GBS obtained from neonatal blood cultures and vaginal swabs from pregnant women. Of 178 isolates from cases of neonatal GBS sepsis collected from 1995 to 1998, 8 and 4.

Direct and indirect bacterial killing functions of neutrophil defensins in lung explants.

Studies of the antimicrobial activity of neutrophil defensins have mostly been carried out in microbiological media, and their effects on the host defense in physiological conditions are unclear. We examined 1) the antibacterial activity of defensins in physiological media with and without lung tissue present, 2) the effect of defensins on hydrogen peroxide (H(2)O(2)) production by lung tissue that had been exposed to bacteria, and 3) the effect of diphenyleneiodonium (DPI), an inhibitor of reactive oxygen species formation, on the antibacterial activity of defensins in the presence of lung tissue. Defensins were incubated with Escherichia coli or Pseudomonas aeruginosa in the absence or presence of primary cultured mouse lung explants.

In vitro activity of a novel ketolide ABT-773 against invasive strains of Streptococcus pneumoniae.

New ketolides such as ABT-773 are a promising group of antibiotics in an era of increasing antibiotic resistance. We tested 704 invasive strains of Streptococcus pneumoniae collected from 1990 to 1998. Overall resistance was 8.

Interspecies recombination contributes minimally to fluoroquinolone resistance in Streptococcus pneumoniae.

Analysis of 71 ciprofloxacin-resistant (MIC > or = 4 microg/ml) Streptococcus pneumoniae clinical isolates revealed only 1 for which the quinolone resistance-determining regions of the parC, parE, and gyrB genes were genetically related to those of viridans group streptococci. Our findings support the occurrence of interspecies recombination of type II topoisomerase genes; however, its contribution to the emergence of quinolone resistance among pneumococci appears to have been minimal.

A nosocomial outbreak of fluoroquinolone-resistant Streptococcus pneumoniae.

Over the course of a 20-month period, in a hospital respiratory ward in which ciprofloxacin was often used as empirical antimicrobial therapy for lower respiratory tract infections (LRTIs), 16 patients with chronic bronchitis developed nosocomial LRTIs caused by penicillin- and ciprofloxacin-resistant Streptococcus pneumoniae (serotype 23 F). The minimum inhibitory concentration (MIC) of ciprofloxacin for all isolates from the first 9 patients was 4 microg/mL, in association with a parC mutation. Isolates from the subsequent 7 patients all had a ciprofloxacin MIC of 16 microg/mL, in association with an additional mutation in gyrA.