Staphylococcus aureus résistant à la méticilline

vignette|Souche de SARM, en microscopie électronique vignette|Microscopie électronique, colorée vignette|Rupture d'un kyste infecté par une souche SARM vignette|Image de microscopie électronique à balayage (fausses couleur) de quatre staphylocoques aureus résistants à la méticilline en train de se faire ingérer par un globule blanc (neutrophile) Le Staphylococcus aureus résistant à la méticilline (SARM) ou, en Methicillin-resistant Staphylococcus aureus (MRSA) est un Staphylococcus aureus (couramment appelé « Staphylocoque doré ») caractérisé par sa résistance à un antibiotique, la méticilline (ou méthicilline). Il cause des infections cutanées et une pneumonie nécrosante potentiellement mortelle, y compris chez des personnes par ailleurs en bonne santé. Presque toutes les souches de SARM expriment une toxine particulière, la LPV ou leucocidine de Panton-Valentine, dite « porogène » (c'est-à-dire induisant des pores dans les parois cellulaires) et capable de tuer certaines cellules, d

Platinum sensitivity of ovarian cancer cells does not influence their ability to induce M2-type macrophage polarization

Agata Mlynska, Mei-Wen Peng

ProblemDevelopment of platinum resistance in ovarian cancer is mediated by both cancer cells and tumor microenvironment. Activation of epithelial-mesenchymal transition program in cancer cells may lead to enrichment for resistant clones. These processes can be affected by tumor-associated macrophages, a highly plastic population of cells that participate in tumor progression and response to treatment by shaping the microenvironment. We aimed to study how platinum resistance influences the crosstalk between macrophages and ovarian cancer cells. Method of studyUsing cisplatin-sensitive ovarian cancer cell line A2780, we developed and characterized cisplatin-resistant A2780Cis and cisplatin and doxorubicin co-resistant A2780Dox cell lines. Next, we set up an indirect coculture system with THP-1 cell line-derived M0-type-, M1-type- and M2-type-like polarized macrophages. We monitored the expression of genes associated with cellular stemness, multidrug resistance, and epithelial-mesenchymal transition in cancer cells, and expression profile of M1/M2 markers in macrophages. ResultsDevelopment of drug resistance in ovarian cancer cell lines was accompanied by increased migration, clonogenicity, and upregulated expression of transcription factors, associated with cellular stemness and epithelial-mesenchymal transition. Upon coculture, we noted that the most relevant changes in gene expression profile occurred in A2780 cells. Moreover, M0- and M1-type macrophages, but not M2-type macrophages, showed significant transcriptional alterations. ConclusionOur results provide the evidence for bidirectional interplay between cancer cells and macrophages. Independent of platinum resistance status, ovarian cancer cells polarize macrophages toward M2-like type, whereas macrophages induce epithelial-mesenchymal transition and stemness-related gene expression profile in cisplatin-sensitive, but not cisplatin-resistant cancer cells.

WILEY2018

Solar photo-Fenton disinfection of 11 antibiotic-resistant bacteria (ARB) and elimination of representative AR genes. Evidence that antibiotic resistance does not imply resistance to oxidative treatment

Stefanos Giannakis, Truong-Thien Melvin Le, César Pulgarin

The emergence of antibiotic resistance represents a major threat to human health. In this work we investigated the elimination of antibiotic resistant bacteria (ARB) by solar light and solar photo-Fenton processes. As such, we have designed an experimental plan in which several bacterial strains (Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae) possessing different drug-susceptible and -resistant patterns and structures (Gram-positive and Gram-negative) were subjected to solar light and the photo-Fenton oxidative treatment in water. We showed that both solar light and solar photo-Fenton processes were effective in the elimination of ARB in water and that the time necessary for solar light disinfection and solar photo-Fenton disinfection were similar for antibiotic-susceptible and antibiotic-resistant strains (mostly 180-240 and 90-120 min, respectively). Moreover, the bacterial structure did not significantly affect the effectiveness of the treatment. Similar regrowth pattern was observed (compared to the susceptible strain) and no development of bacteria with higher drug-resistance values was found in waters after any treatment. Finally, both processes were effective to reduce AR genes (ARGs), although solar photo-Fenton was more rapid than solar light. In conclusion, the solar photo-Fenton process ensured effective disinfection of ARB and elimination of ARGs in water (or wastewater) and is a potential mean to ensure limitation of ARB and ARG spread in nature. (C) 2018 Elsevier Ltd. All rights reserved.

PERGAMON-ELSEVIER SCIENCE LTD2018

A benzamide-dependent ftsZ mutant reveals residues crucial for Z-ring assembly

David William Adams

In almost all bacteria, cell division is co-ordinated by the essential tubulin homologue FtsZ and represents an attractive but as yet unexploited target for new antibiotics. The benzamides, e.g. PC190723, are potent FtsZ inhibitors that have the potential to yield an important new class of antibiotic. However, the evolution of resistance poses a challenge to their development. Here we show that a collection of PC190723-resistant and -dependent strains of Staphylococcus aureus exhibit severe growth and morphological defects, questioning whether these ftsZ mutations would be clinically relevant. Importantly, we show that the most commonly isolated substitution remains sensitive to the simplest benzamide 3-MBA and likely works by occluding compound binding. Extending this analysis to Bacillus subtilis, we isolated a novel benzamide-dependent strain that divides using unusual helical division events. The ftsZ mutation responsible encodes the substitution of a highly conserved residue, which lies outside the benzamide-binding site and forms part of an interface between the N- and C-terminal domains that we show is necessary for normal FtsZ function. Together with an intragenic suppressor mutation that mimics benzamide binding, the results provide genetic evidence that benzamides restrict conformational changes in FtsZ and also highlights their utility as tools to probe bacterial division.

Wiley-Blackwell2016

Platinum sensitivity of ovarian cancer cells does not influence their ability to induce M2-type macrophage polarization

Agata Mlynska, Mei-Wen Peng

WILEY2018