A glimpse on Staphylococcus aureus translation machinery and its control

© 2016, Pleiades Publishing, Inc.Staphylococcus aureus is a major opportunistic and versatile pathogen. Because the bacteria rapidly evolve multi-resistances towards antibiotics, there is an urgent need to find novel targets and alternative strategies to cure bacterial infections. Here, we provide a brief overview on the knowledge acquired on S. aureus ribosomes, which is one of the major antibiotic targets. We will show that subtle differences exist between the translation at the initiation step of Gram-negative and Gram-positive bacteria although their ribosomes display a remarkable degree of resemblance. In addition, we will illustrate using specific examples the diversity of mechanisms controlling translation initiation in S. aureus that contribute to shape the expression of the virulence factors in a temporal and dynamic manner

Selective estrogen receptor modulators decrease the production of interleukin-6 and interferon-γ-inducible protein-10 by astrocytes exposed to inflammatory challenge in vitro

Expression of proinflammatory molecules by glial cells is involved in the pathophysiological changes associated with chronic neurological diseases. Under pathological conditions, astrocytes release a number of proinflammatory molecules, such as interleukin-6 (IL-6) and interferon-γ-inducible protein-10 (IP-10). The ovarian hormone estradiol exerts protective effects in the central nervous system that, at least in part, may be mediated by a reduction of local inflammation. This study was designed to assess whether estradiol affects the production of IL-6 and IP-10 by primary cultures of newborn mice astrocytes exposed to lipopolysaccharide (LPS), a bacterial endotoxin known to cause neuroinflammation. In addition, the possible anti-inflammatory effect of several selective estrogen receptor modulators (SERMs) was also assessed. LPS induced an increase in the expression of IL-6 and IP-10 mRNA levels in astrocytes and an increase in IL-6 and IP-10 protein levels in the culture medium. These effects of LPS were impaired by estradiol and by the four SERMs tested in our study: tamoxifen, raloxifene, ospemifene, and bazedoxifene. All SERMs tested showed a similar effect on IL-6 and IP-10 mRNA levels, but raloxifene and ospemifene were more effective than tamoxifen and bazedoxifene in reducing protein levels in LPS-treated cultures. Finally, we report that news SERMs, ospemifene and bazedoxifene, exert anti-inflammatory actions by a mechanism involving classical estrogen receptors and by the inhibition of LPS-induced NFjB p65 transactivation. The results suggest that estrogenic compounds may be candidates to counteract brain inflammation under neurodegenerative conditions by targeting the production and release of proinflammatory molecules by astrocytes. © 2009 Wiley-Liss, Inc.Peer Reviewe

An in vitro experimental model of neuroinflammation: The induction of interleukin-6 in murine astrocytes infected with Theiler's murine encephalomyelitis virus, and its inhibition by oestrogenic receptor modulators

This paper describes an experimental model of neuroinflammation based on the production of interleukin-6 (IL-6) by neural glial cells infected with Theiler's murine encephalomyelitis virus (TMEV). Production of IL-6 mRNA in mock-infected and TMEV-infected SJL/J murine astrocytes was examined using the Affymetrix murine genome U74v2 DNA microarray. The IL-6 mRNA from infected cells showed an eightfold increase in hybridization to a sequence encoding IL-6 located on chromosome number 5. Quantitative real-time reverse transcription PCR (qPCR) was used to study the regulation of IL-6 expression. The presence of IL-6 in the supernatants of TMEV-infected astrocyte cultures was quantified by ELISA and found to be weaker than in cultures of infected macrophages. The IL-6 was induced by whole TMEV virions, but not by Ad.βGal adenovirus, purified TMEV capsid proteins, or UV-inactivated virus. Two recombinant inflammatory cytokines, IL-1α and tumour necrosis factor-α were also found to be potent inducers of IL-6. The secreted IL-6 was biologically active because it fully supported B9 hybridoma proliferation in a [3H]thymidine incorporation bioassay. The cerebrospinal fluid of infected mice contained IL-6 during the acute encephalitis phase, peaking at days 2-4 post-infection. Finally, this in vitro neuroinflammation model was fully inhibited, as demonstrated by ELISA and qPCR, by five selective oestrogen receptor modulators. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.Peer Reviewe

Theiler’s virus infection provokes the overexpression of genes coding for the chemokine Ip10 (CXCL10) in SJL/J murine astrocytes, which can be inhibited by modulators of estrogen receptors

© 2014, Journal of NeuroVirology, Inc. Theiler’s murine encephalomyelitis virus (TMEV) induces demyelination in susceptible strains of mice (SJL/J) through an immunopathological process that is mediated by CD4+ Th1 T cell. These T cells are chemoattracted to the central nervous system by chemokines. Hence, in this study, we focused on the production of the chemokine “interferon-gamma-inducible protein 10 kDa,” or IP-10/CXCL10, by cultured SJL/J mouse astrocytes infected with the BeAn strain of TMEV and its capacity to attract activated T cells. The analysis of the whole murine genome by DNA hybridization with cRNAs from mock- and TMEV-infected cultures revealed the upregulation of six sequences that potentially encode for CXCL10. This increased CXCL10 expression was validated by PCR and qPCR. The presence of this chemokine was further demonstrated by enzyme-linked immunoassay (ELISA). Significantly, astrocytes from BALB/c mice, a strain resistant to demyelination, did not produce CXCL10. The secreted CXCL10 was biologically active, inducing chemoattraction of activated lymphocytes. The inflammatory cytokines, IL-1α, IFN-γ, and TNF-α, were strong inducers of CXCL10 in astrocytes. Serum from TMEV-infected SJL/J but not BALB/c mice contains CXCL10, the levels of which peak at the onset of the clinical disease. Finally, this in vitro inflammation model was fully inhibited by 17β-estradiol and four selective estrogen receptor modulators, as demonstrated by ELISA and qPCR.Peer Reviewe

A glimpse on Staphylococcus aureus translation machinery and its control

© 2016, Pleiades Publishing, Inc.Staphylococcus aureus is a major opportunistic and versatile pathogen. Because the bacteria rapidly evolve multi-resistances towards antibiotics, there is an urgent need to find novel targets and alternative strategies to cure bacterial infections. Here, we provide a brief overview on the knowledge acquired on S. aureus ribosomes, which is one of the major antibiotic targets. We will show that subtle differences exist between the translation at the initiation step of Gram-negative and Gram-positive bacteria although their ribosomes display a remarkable degree of resemblance. In addition, we will illustrate using specific examples the diversity of mechanisms controlling translation initiation in S. aureus that contribute to shape the expression of the virulence factors in a temporal and dynamic manner

A glimpse on Staphylococcus aureus translation machinery and its control

© 2016, Pleiades Publishing, Inc.Staphylococcus aureus is a major opportunistic and versatile pathogen. Because the bacteria rapidly evolve multi-resistances towards antibiotics, there is an urgent need to find novel targets and alternative strategies to cure bacterial infections. Here, we provide a brief overview on the knowledge acquired on S. aureus ribosomes, which is one of the major antibiotic targets. We will show that subtle differences exist between the translation at the initiation step of Gram-negative and Gram-positive bacteria although their ribosomes display a remarkable degree of resemblance. In addition, we will illustrate using specific examples the diversity of mechanisms controlling translation initiation in S. aureus that contribute to shape the expression of the virulence factors in a temporal and dynamic manner

A glimpse on Staphylococcus aureus translation machinery and its control

International audienc

A method to map changes in bacterial surface composition induced by regulatory RNAs in Escherichia coli and Staphylococcus aureus

International audienc