Panton-Valentine Leukocidin Is Not the Primary Determinant of Outcome for Staphylococcus aureus Skin Infections: Evaluation from the CANVAS Studies

The impact of Panton-Valentine leukocidin (PVL) on the severity of complicated skin and skin structure infections (cSSSI) caused by Staphylococcus aureus is controversial. We evaluated potential associations between clinical outcome and PVL presence in both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) isolates from patients enrolled in two large, multinational phase three clinical trials assessing ceftaroline fosamil for the treatment of cSSSI (the CANVAS 1 and 2 programs). Isolates from all microbiologically evaluable patients with monomicrobial MRSA or MSSA infections (n = 473) were genotyped by PCR for pvl and underwent pulsed-field gel electrophoresis (PFGE). Genes encoding pvl were present in 266/473 (56.2%) isolates. Infections caused by pvl-positive S. aureus were associated with younger patient age, North American acquisition, and presence of major abscesses (P<0.001 for each). Cure rates of patients infected with pvl-positive and pvl-negative S. aureus were similar overall (93.6% versus 92.8%; P = 0.72), and within MRSA-infected (94.5% vs. 93.1%; P = 0.67) and MSSA-infected patients (92.2% vs. 92.7%; P = 1.00). This finding persisted after adjustment for multiple patient characteristics. Outcomes were also similar when USA300 PVL+ and non-USA300 PVL+ infections were compared. The results of this contemporary, international study suggest that pvl presence was not the primary determinant of outcome in patients with cSSSI due to either MRSA or MSSA

Two Genes on A/J Chromosome 18 Are Associated with Susceptibility to Staphylococcus aureus Infection by Combined Microarray and QTL Analyses

Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that loci on chromosomes 8, 11, and 18 influence susceptibility to S. aureus sepsis in A/J mice. We then used two candidate gene selection strategies to identify genes on these three chromosomes associated with S. aureus susceptibility, and targeted genes identified by both gene selection strategies. First, we used whole genome transcription profiling to identify 191 (56 on chr. 8, 100 on chr. 11, and 35 on chr. 18) genes on our three chromosomes of interest that are differentially expressed between S. aureus-infected A/J and C57BL/6J. Second, we identified two significant quantitative trait loci (QTL) for survival post-infection on chr. 18 using N2 backcross mice (F1 [C18A]×C57BL/6J). Ten genes on chr. 18 (March3, Cep120, Chmp1b, Dcp2, Dtwd2, Isoc1, Lman1, Spire1, Tnfaip8, and Seh1l) mapped to the two significant QTL regions and were also identified by the expression array selection strategy. Using real-time PCR, 6 of these 10 genes (Chmp1b, Dtwd2, Isoc1, Lman1, Tnfaip8, and Seh1l) showed significantly different expression levels between S. aureus-infected A/J and C57BL/6J. For two (Tnfaip8 and Seh1l) of these 6 genes, siRNA-mediated knockdown of gene expression in S. aureus–challenged RAW264.7 macrophages induced significant changes in the cytokine response (IL-1 β and GM-CSF) compared to negative controls. These cytokine response changes were consistent with those seen in S. aureus-challenged peritoneal macrophages from CSS 18 mice (which contain A/J chromosome 18 but are otherwise C57BL/6J), but not C57BL/6J mice. These findings suggest that two genes, Tnfaip8 and Seh1l, may contribute to susceptibility to S. aureus in A/J mice, and represent promising candidates for human genetic susceptibility studies

The role of autonomous free radical production in the killing of Escher[ich]ia coli by chemical biocide treatments

Available from British Library Document Supply Centre- DSC:DXN061047 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

EFFECTS OF ALPHA-MANGOSTIN AND CITRONELLA OIL AGAINST ACNE CAUSING BACTERIA

Objective: This study assessed the effects of alpha-mangostin (AM) and citronella oil (CO) working alone or in combination against Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus). Methods: The screening for antibacterial activity of AM and CO against P. acnes and S. aureus was carried out using the disk diffusion method. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of these two substances were determined using the broth microdilution method. The fractional inhibitory concentration indices (FICI) of a combination of AM and CO were obtained by checkerboard dilution assay. Results: The results showed that alpha-mangostin and citronella oil do indeed fight against P. acnes and S. aureus. The MICs and MBCs of AM against P. acnes and S. aureus were the same at 6.25 and 50 µg/ml, respectively. Both the MIC and the MBC of CO against P. acnes were 27.81µg/ml. The MIC and the MBC of CO against S. aureus were 112.13 and 224.25 µg/ml, respectively. The FICI of a combination of AM and CO against P. acnes and S. aureus were 2.00, indicating indifferent interaction with no additional inhibitory effect. Conclusion: AM and CO are very effective against P. acnes and S. aureus, nevertheless their effect when used together was indifferent from using alone. Further research may find that either or both of these substances combined with yet a different natural agent could provide synergy againstP. acnes and S. aureus

Larvicidal activity of endocarp and seed crude extracts of Dracaena loureiri Gagnep against Aedes aegypti (L.) mosquito

Objective: To evaluate the larvicidal activity of the ethanolic and aqueous extracts of the endocarp and seeds of Dracaena loureiri (D. loureiri) against the dengue mosquito vector, Aedes aegypti. Methods: Bioassays were performed by exposing late third-stage to early fourth-stage larvae of Aedes aegypti to various concentrations of the extracts from D. loureiri. The larval mortality was observed after 24- and 48-h exposure. Results: The larvicidal bioassay in this study demonstrated that the ethanolic endocarp extract was the most effective with the LC50 value of 84.00 mg/L after 24 h exposure and < 50 mg/L after 48 h exposure. Extracts from the other parts of the plant were significantly less effective as a larvicide. Conclusions: The ethanolic endocarp extract of D. loureiri demonstrated effective larvicidal activity. It is an alternative source for developing a novel larvicide for controlling this mosquito species

Prevalence and virulence factors of Candida spp. associated with blow flies

Objective: To investigate the prevalence of Candida spp. and the virulence factors of Candida albicans (C. albicans) isolated from external surfaces of blow flies collected from Mae Sot, Tak Province, Thailand. Methods: The blow flies were collected by sterile sweep nets from three areas in Mae Sot. Yeast isolation was first performed on Sabouraud dextrose agar (SDA) supplemented with chloramphenicol and cycloheximide. The yeast isolates were then identified by using chromogenic agar, a yeast identification test kit, a germ tube formation test and a carbohydrate utilization test. The β-hemolysis was determined on 7% sheep blood agar, while phospholipase activity was measured on SDA agar supplemented with 10% egg yolk suspension. Antifungal susceptibility testing was determined by broth micro-dilution testing against ketoconazole and amphotericin B. Results: The prevalence rate of Candida spp. on the external surfaces of the blow flies was 78.1%. All C. albicans isolated from the blow fly demonstrated β-hemolysin and potent phospholipase activities and 47.1% of C. albicans were resistant to ketoconazole with MIC values 128 μg/mL. Conclusions: The results indicate that blow flies could play an essential role in the transmission of potentially pathogenic and antifungal resistant C. albicans into the environment. Further investigation on other virulence factors and genetic relatedness among isolates from the blow flies, the environment and clinical specimens is required to confirm this role

Baseline characteristics of 473 patients with <i>S. aureus</i> complicated skin and skin structure infections (cSSSI) stratified by methicillin-resistance and <i>pvl</i> gene status of the infecting pathogen.

*<p> = P-Value from generalized 2-sided Fishers Exact Test. Calculated using 7×2 table (^∧), 4×2 table (§) and 3×2 table (±).</p>**<p> = P-Value from 2-sided T-test.</p>***<p> = P-value from Wilcoxon Rank Sum test.</p><p>1 = Subjects with missing data were not included in these summaries.</p