Project description:Hypersensitivity reactions are rare, but potentially severe adverse effects of sulfonamide antibiotics. Increased in vitro toxicity of lymphocytes, primarily CD8+ T cells, to sulfonamide drug metabolites as been proposed as a marker for sulfonamide hypersensitivity, but the mechanisms underlying this marker are unknown. Therefore, we used microarrays to compare RNA expression of CD8+ T cell-enriched peripheral blood mononuclear cells of human patients who have had a hypersensitivity (HS) reaction to sulfonamide antibiotics vs. patients who have been tolerant (TOL) to a course of sulfonamide antibiotics.
Project description:Potentiated sulfonamide antibiotics such as trimethoprim/sulfamethoxazole (cotrimoxazole or TMP/SMX) remain the drugs of choice for treatment and prevention of Pneumocystis jiroveci pneumonia, toxoplasma encephalitis, and Isospora infections in HIV infection (aidsinfo.nih.gov). However, HIV-infected patients show a markedly increased risk of delayed hypersensitivity (HS) reactions to TMP/SMX (20-57% incidence) when compared to the general population (3% incidence). The typical manifestation is maculopapular rash with or without fever, and TMP/SMX is the most common cause of cutaneous drug reactions in HIV-infected patients TMP/SMX can also lead to thrombocytopenia, hepatotoxicity, and bullous skin eruptions in more severely affected patients. The risk of sulfonamide HS increases with progression to AIDS, with higher risk seen at lower CD4+ counts. This risk has been attributed, at least in part, to acquired alterations in SMX drug disposition in HIV infection. We hypothesized that HIV infection leads to impaired hepatic SMX detoxification or enhanced SMX bioactivation pathways, which may contribute to the increased incidence of sulfonamide HS. We addressed this question using liver tissue from SIVmac239-infected macaques, a well accepted model of HIV infection. The aim of this study was to evaluate differences in the hepatic expression and activity of SMX biotransformation pathways from drug naïve SIV-infected macaques compared to sex- and age-matched uninfected controls.
Project description:The human pathogenic bacterium Listeria monocytogenes was exposed to antibiotics both during clinical treatment and as a saprophyte. As one of the keys to successful treatment is continued antibiotic sensitivity, the purpose of this study was to determine if exposure to sublethal antibiotic concentrations would affect the bacterial physiology and potentially induce tolerance to antibiotics. Transcriptomic analyses demonstrated that each of four antibiotics caused a compound-specific gene expression pattern related to (the) mode-of-action of the particular antibiotic. All four antibiotics caused the same changes in expression of several metabolic genes indicating a shift from aerobic to anaerobic metabolism driven by the induction of lmo1634 and the repression of alsA and lmo1992. This shift in metabolism could be a survival strategy in response to antibiotics and is further supported by the observation that a Δlmo1634 mutant was more sensitive to bactericidal antibiotics. The monocin locus encoding a cryptic prophage was induced by co-trimoxazole and repressed by ampicillin and gentamicin. This expression pattern correlated with the observed antibiotic-dependent biofilm formation, indicating a role of monocin in antibiotic-induced biofilm formation and a ΔlmaDCBA mutant confirmed this correlation. Thus, sublethal concentrations of antibiotics caused metabolic and physiological changes indicating that the organism is preparing to withstand lethal concentrations of antibiotics.
2016-06-01 | GSE65558 | GEO
Project description:Biological and non-biological treatment for anaerobic digester overloaded with glucose
Project description:The human pathogenic bacterium Listeria monocytogenes was exposed to antibiotics both during clinical treatment and as a saprophyte. As one of the keys to successful treatment is continued antibiotic sensitivity, the purpose of this study was to determine if exposure to sublethal antibiotic concentrations would affect the bacterial physiology and potentially induce tolerance to antibiotics. Transcriptomic analyses demonstrated that each of four antibiotics caused a compound-specific gene expression pattern related to (the) mode-of-action of the particular antibiotic. All four antibiotics caused the same changes in expression of several metabolic genes indicating a shift from aerobic to anaerobic metabolism driven by the induction of lmo1634 and the repression of alsA and lmo1992. This shift in metabolism could be a survival strategy in response to antibiotics and is further supported by the observation that a Îlmo1634 mutant was more sensitive to bactericidal antibiotics. The monocin locus encoding a cryptic prophage was induced by co-trimoxazole and repressed by ampicillin and gentamicin. This expression pattern correlated with the observed antibiotic-dependent biofilm formation, indicating a role of monocin in antibiotic-induced biofilm formation and a ÎlmaDCBA mutant confirmed this correlation. Thus, sublethal concentrations of antibiotics caused metabolic and physiological changes indicating that the organism is preparing to withstand lethal concentrations of antibiotics. Investigation of mRNA and sRNA expression profiles of L. monocytogenes EGD cells exposed to sublethal concentrations of four different antibiotics i.e. ampicillin, tetracycline, gentamicin and co-trimoxazole for 3h.
Project description:Freshwater environments such as rivers receive effluent discharges from wastewater treatment plants, representing a potential hotspot for antibiotic resistance genes (ARGs). These effluents also contain low levels of different antimicrobials including biocides and antibiotics such as sulfonamides that can be frequently detected in rivers. The impact of such exposure on ARG prevalence and microbial diversity of riverine environment is unknown, so the aim of this study was to investigate the release of a sub-lethal concentration (<4 g L-1) of the sulfonamide compound sulfamethoxazole (SMX) on the river bacterial microbiome using a microflume system. This system was a semi-natural in-vitro microflume using river water (30 L) and sediment, with circulation to mimic river flow. A combination of ‘omics’ approaches were conducted to study the impact of SMX exposure on the microbiomes within the microflumes. Metaproteomics did not show differences in ARGs expression with SMX exposure in water.