Hydroxyethoxy phenyl butanone, a new cosmetic preservative, does not cause bacterial cross-resistance to antimicrobials

Introduction. Biocide-induced cross-resistance to antimicrobials in bacteria has been described and is a concern for regulators. We have recently reported on a new protocol to predict the propensity of biocide to induce phenotypic resistance in bacteria. Aim. To measure bacterial propensity to develop antimicrobial resistance following exposure to a new cosmetic preservative developed by L’Oréal R and I. Methodology. Well-established antimicrobials including triclosan (TRI) and benzalkonium chloride (BZC) and a new molecule hydroxyethoxy phenyl butanone (HEPB) were investigated for their antimicrobial efficacy, effect on bacterial growth, and their potential to induce resistance to chemotherapeutic antibiotics using a new predictive protocol. Results. The use of this predictive protocol with Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa showed that TRI and BZC significantly affected bacterial growth, MICs and minimum bactericidal concentrations (MBCs). There was no change in antibiotic susceptibility profile following exposure to BZC, but E. coli became intermediate resistant to tobramycin following treatment with TRI (0.00002 % w/v). HEPB did not change the antimicrobial susceptibility profile in P. aeruginosa and S. aureus but E. coli became susceptible to gentamicin. TRI exposure resulted in bacterial susceptibility profile alteration consistent with the literature and confirmed the use of TRI as a positive control in such a test. Conclusion. Data produced on the propensity of a molecule to induce bacterial resistance is useful and appropriate when launching a new preservative

Mapping the efficacy and mode of action of ethylzingerone [4-(3-ethoxy-4-hydroxyphenyl) butan-2-one] as an active agent against Burkholderia bacteria

Burkholderia cepacia complex (Bcc) bacteria are intrinsically antimicrobial-resistant opportunistic pathogens and key risk species in the contamination of nonfood industrial products. New agents and formulations to prevent growth of Burkholderia in home care (cleaning agents) and personal-care (cosmetics and toiletries) products are required. We characterized how ethylzingerone [4-(3-ethoxy-4-hydroxyphenyl) butan-2-one] (HEPB) acts as a preservative with activity against Burkholderia species encountered in industry. Burkholderia (n = 58) and non-Burkholderia (n = 7) bacteria were screened for susceptibility to HEPB, and its mode of action and resistance were determined for a model Burkholderia vietnamiensis strain using transposon mutagenesis, transcriptomics, and genome resequencing analysis. The susceptibility of Burkholderia spp. to HEPB (MIC = 0.45% ± 0.11% [wt/vol]; MBC = 0.90% ± 0.3% [wt/vol]) was characterized, with limited inter- and intraspecies differences. HEPB (1% [wt/vol]) was rapidly bactericidal, producing a 6-log reduction in viability within 4 h. Spontaneous resistance to HEPB did not develop, but transient phenotypes with altered growth characteristics and susceptibility to antibiotics were identified after prolonged exposure to sublethal HEPB concentrations. Transposon mutagenesis and RNA-sequencing analysis identified multiple genetic pathways associated with HEPB exposure, including stress response mechanisms, altered permeability, regulation of intracellular pH, damage and repair of intracellular components, and alteration and repair of lipopolysaccharides. Key pathways included the stringent response, homeostasis of intracellular pH by the kdp operon, protection against electrophiles by KefC, and repair of oxidized proteins by methionine sulfoxide reductase enzymes. In summary, we show that HEPB has potent, targeted efficacy against Burkholderia bacteria without promoting wider stable antimicrobial resistance. The mode of action of HEPB against Burkholderia is multifactorial, but killing by intracellular oxidation is a key mechanism of this promising agent

Proteins of the H-NS family : differential regulation of the LEE5 operon by paralogue proteins H-NS and Ler in Enteropathogenic E. coli (EPEC)

Le génome des bactéries vivantes n’est pas une entité statique mais au contraire c’est quelque chose très dynamique évoluant avec le temps. Les bactéries évoluent en acquérant par transfert horizontal des gènes du matériel génétique. C’est le cas des EPEC qui ont acquis l’îlot LEE via ce mécanisme. La protéine H-NS joue un rôle important dans la reconnaissance de cet ADN étranger, dans la liaison à cet ADN et dans la répression de son expression quand ce n’est pas en profit du « fitness » de la bactérie. Comme résultat H-NS régule la majorité des gènes associés à la virulence chez les entérobactéries Salmonella, Yersinia et les EPEC. Les EPEC possèdent une protéine paralogue à H-NS et codée dans le premier opéron de leur îlot LEE, il s’agit de la protéine Ler. Une fois exprimée Ler induit l’expression des 4 opérons restant de la région parmi lesquels LEE5. Ler partage une grande homologie avec H-NS surtout au niveau de leurs domaines de reconnaissance de l’ADN. Malgré cette homologie H-NS réprime LEE5 tandis que Ler l’active. De plus si H-NS est un régulateur global agissant sur plus de 500 gènes chez E. coli Ler est une protéine spécifique qui ne va agir que sur un petit nombre de promoteurs tous impliqués dans la virulence L’étude qualitative et quantitative de l’interaction de H-NS et de Ler avec la région promotrice de LEE5 montre qu’elles partagent globalement les mêmes sites de fixation sur des régions étendues en amont et en aval du +1 de la transcription. Ces sites de fixation sont bien définis d’une dizaine de paires de bases. L’affinité de ces sites pour H-NS est variable. Trois sites de haute affinité pour H-NS ont été identifiés. La séquence de ces sites est similaire à celle du site consensus élaboré en étudiant le promoteur proU(Bouffartigues et al - 2007). Des différences dans l’interaction de ces deux protéines avec le promoteur LEE5 résident surtout autour du +1 et des boîtes -10 et -35. Il s’agit de la première étude comparant la fixation de H-NS et de Ler sur des régions étendues de ce promoteur dans le but d’expliquer la régulation différentielle de ces deux protéines paralogues. L’étude de l’expression de LEE5 in vivo nous a permis de proposer que le mécanisme essentiel d’action de Ler est dirigé contre la répression induite par H-NS et que le taux maximum d’expression du promoteur LEE5 wtobservé dans la souche mutante pour hnsen présence de Ler (en comparaison avec la souche double mutante où Ler est absente) n’est pas dû à une activation directe par Ler mais plutôt à une répression par StpA, sensible à la mutation des sites de haute affinité de H-NS.The genes of the LEE5 operon of enteropathogenic E.coliencode for proteinsthat are essential for their virulence. Their expression istightlyregulated, with H-NS silencing the transcriptional expression of LEE5 while Ler, product of the first operon of thispathogenicityislandcancounteract the silencing of H-NS. We show that H-NS and Ler use the samebinding sites on the LEE5 promoterin vitro. However, around the transcription start site differences in DNA constraints are detectabledepending on the presence of H-NS or Ler. Modification of the central AT bases, characteristic of H-NS consensus binding sites, affect the binding of bothproteinsin vitro and the expression in vivo of the LEE5 promoter. Additionallywe show that an additionalrepressor, the H-NS homologue StpA, isimplicated in the LEE5 regulationleading to a new model of how Ler canrelieve the H-NS imposedrepression on the LEE5 promote

Etude des protéines de la famille H-NS : régulation différentielle des opérons LEE par les protéines H-NS et Ler chez les EPEC

The genes of the LEE5 operon of enteropathogenic E.coliencode for proteinsthat are essential for their virulence. Their expression istightlyregulated, with H-NS silencing the transcriptional expression of LEE5 while Ler, product of the first operon of thispathogenicityislandcancounteract the silencing of H-NS. We show that H-NS and Ler use the samebinding sites on the LEE5 promoterin vitro. However, around the transcription start site differences in DNA constraints are detectabledepending on the presence of H-NS or Ler. Modification of the central AT bases, characteristic of H-NS consensus binding sites, affect the binding of bothproteinsin vitro and the expression in vivo of the LEE5 promoter. Additionallywe show that an additionalrepressor, the H-NS homologue StpA, isimplicated in the LEE5 regulationleading to a new model of how Ler canrelieve the H-NS imposedrepression on the LEE5 promoterLe génome des bactéries vivantes n’est pas une entité statique mais au contraire c’est quelque chose très dynamique évoluant avec le temps. Les bactéries évoluent en acquérant par transfert horizontal des gènes du matériel génétique. C’est le cas des EPEC qui ont acquis l’îlot LEE via ce mécanisme. La protéine H-NS joue un rôle important dans la reconnaissance de cet ADN étranger, dans la liaison à cet ADN et dans la répression de son expression quand ce n’est pas en profit du « fitness » de la bactérie. Comme résultat H-NS régule la majorité des gènes associés à la virulence chez les entérobactéries Salmonella, Yersinia et les EPEC. Les EPEC possèdent une protéine paralogue à H-NS et codée dans le premier opéron de leur îlot LEE, il s’agit de la protéine Ler. Une fois exprimée Ler induit l’expression des 4 opérons restant de la région parmi lesquels LEE5. Ler partage une grande homologie avec H-NS surtout au niveau de leurs domaines de reconnaissance de l’ADN. Malgré cette homologie H-NS réprime LEE5 tandis que Ler l’active. De plus si H-NS est un régulateur global agissant sur plus de 500 gènes chez E. coli Ler est une protéine spécifique qui ne va agir que sur un petit nombre de promoteurs tous impliqués dans la virulence L’étude qualitative et quantitative de l’interaction de H-NS et de Ler avec la région promotrice de LEE5 montre qu’elles partagent globalement les mêmes sites de fixation sur des régions étendues en amont et en aval du +1 de la transcription. Ces sites de fixation sont bien définis d’une dizaine de paires de bases. L’affinité de ces sites pour H-NS est variable. Trois sites de haute affinité pour H-NS ont été identifiés. La séquence de ces sites est similaire à celle du site consensus élaboré en étudiant le promoteur proU(Bouffartigues et al - 2007). Des différences dans l’interaction de ces deux protéines avec le promoteur LEE5 résident surtout autour du +1 et des boîtes -10 et -35. Il s’agit de la première étude comparant la fixation de H-NS et de Ler sur des régions étendues de ce promoteur dans le but d’expliquer la régulation différentielle de ces deux protéines paralogues. L’étude de l’expression de LEE5 in vivo nous a permis de proposer que le mécanisme essentiel d’action de Ler est dirigé contre la répression induite par H-NS et que le taux maximum d’expression du promoteur LEE5 wtobservé dans la souche mutante pour hnsen présence de Ler (en comparaison avec la souche double mutante où Ler est absente) n’est pas dû à une activation directe par Ler mais plutôt à une répression par StpA, sensible à la mutation des sites de haute affinité de H-NS

الاستراتيجية الدولية وآثرها على المشرق العربي حتى عام 1921

اتبعت الدول العظمى في أوروبا استراتيجية توازن القوى، منذ القرن السادس عشر، القائمة على التحالفات أو المحاور، والمبنية على يد الرأسمالية، الأمر الذي دفع بهذه القوى للتوسع الاستعماري، لاسيما في منطقة المشرق العربي، معتمدة على تفوقها العسكري. لتظهر سياسة المؤامرات بعد مؤتمر فيينا عام 1815، أدت إلى تغيير طبيعة التوازن الدولي، وبنشاط سياسة الاحلاف الأوروبية للدول العظمى، في بداية القرن العشرين، وبدء تسابق التسلح فيما بينها، لاسيما، ألمانيا وبريطانيا، مما أدى إلى انقسام أوروبا إلى معسكرين الأول قادته ألمانيا والثاني بريطانيا، وبالتالي أدى إلى نشوب الحرب العالمية الأولى عام 1914. وكان إعلان الدولة العثمانية وقوفها بالحرب ألمانيا، الخطوة الأولى، بنظر بريطانيا وفرنسا، على طريق ولادة الشرق الأوسط الجديد، بعد أن كانت سياستها لمدة مئة سنة هي الحفاظ على وحدة الإمبراطورية العثمانية، مما أدى إلى تقسيم المشرق العربي، وظهور أربعة دول، هي سوريا ولبنان وفلسطين وشرقي الأردن والعراق

MQC-MB: multiphoton quantum communication using multiple-beam concept in free space optical channel

Multiphoton Quantum Key Distribution (QKD) has recently been proposed to exchange the secret keys using the rotational of polarization over a multi-stage protocol. It has the ability to outperform the weaknesses of a single photon QKD by improving the generation of key rate and distance range. This paper investigates the theoretical aspects of multiphoton QKD protocol’s performance over free space optic (FSO) networks. The most common setup for quantum communication is the single-beam approach. However, the single-beam setup has limitations in terms of high geometrical loss. In this paper, the symmetry multiple-beam for quantum communication which is called as Multiphoton Quantum Communication-Multiple Beam (MQC-MB) is proposed to transmit the multiphoton from the sender to the receiver in order to minimize the impact of geometrical loss that is faced by the single-beam setup. The analysis was carried out through mathematical analysis by establishing the FSO quantum model with the effects of atmospheric and geometrical loss as well as considering atmospheric turbulence modeled by log-normal distribution. The design criteria of FSO, such as the transmitter, receiver, beam divergence, and diameter of apertures, are analytically investigated. The numerical results demonstrate that the MQC-MB outperforms the single-beam in terms of reducing channel loss by about 8 dB and works well under strong turbulence channel. Furthermore, the MQC-MB reduces the quantum bit error rate (QBER) and improves the secret key rate (SKR) as compared to the single-beam system even though the distance between the sender and receiver increases

H-NS Silencing of the Salmonella Pathogenicity Island 6-Encoded Type VI Secretion System Limits Salmonella enterica Serovar Typhimurium Interbacterial Killing

International audienceThe secretion of bacterial toxin proteins is achieved by dedicated machineries called secretion systems. The type VI secretion system (T6SS) is a widespread versatile machine used for the delivery of protein toxins to both prokaryotic and eukaryotic cells. In Salmonella enterica serovar Typhimurium, the expression of the T6SS genes is activated during macrophage or mouse infection. Here, we show that the T6SS gene cluster is silenced by the histone-like nucleoid structuring H-NS protein using a combination of reporter fusions, electrophoretic mobility shift assays, DNase footprinting, and fluorescence microscopy. We further demonstrate that derepression of the S. Typhimurium T6SS genes induces T6SS-dependent intoxication of competing bacteria. Our results suggest that relieving T6SS H-NS silencing may be used as a sense-and-kill mechanism that will help S. Typhimurium to homogenize and synchronize the microbial population to gain efficiency during infection

Bacterial-chromatin structural proteins regulate the bimodal expression of the locus of enterocyte effacement (LEE) pathogenicity island in enteropathogenic Escherichia coli

No commentInternational audienceIn enteropathogenic Escherichia coli (EPEC), the locus of enterocyte effacement (LEE) encodes a type 3 secretion system (T3SS) essential for pathogenesis. This pathogenicity island comprises five major operons (LEE1 to LEE5), with the LEE5 operon encoding T3SS effectors involved in the intimate adherence of bacteria to enterocytes. The first operon, LEE1, encodes Ler (LEE-encoded regulator), an H-NS (nucleoid structuring protein) paralog that alleviates the LEE H-NS silencing. We observed that the LEE5 and LEE1 promoters present a bimodal expression pattern, depending on environmental stimuli. One key regulator of bimodal LEE1 and LEE5 expression is ler expression, which fluctuates in response to different growth conditions. Under conditions in vitro considered to be equivalent to nonoptimal conditions for virulence, the opposing regulatory effects of H-NS and Ler can lead to the emergence of two bacterial subpopulations. H-NS and Ler share nucleation binding sites in the LEE5 promoter region, but H-NS binding results in local DNA structural modifications distinct from those generated through Ler binding, at least in vitro. Thus, we show how two nucleoidbinding proteins can contribute to the epigenetic regulation of bacterial virulence and lead to opposing bacterial fates. This finding implicates for the first time bacterialchromatin structural proteins in the bimodal regulation of gene expression. IMPORTANCE Gene expression stochasticity is an emerging phenomenon in microbiology. In certain contexts, gene expression stochasticity can shape bacterial epigenetic regulation. In enteropathogenic Escherichia coli (EPEC), the interplay between H-NS (a nucleoid structuring protein) and Ler (an H-NS paralog) is required for bimodal LEE5 and LEE1 expression, leading to the emergence of two bacterial subpopulations (with low and high states of expression). The two proteins share mutual nucleation binding sites in the LEE5 promoter region. In vitro, the binding of H-NS to the LEE5 promoter results in local structural modifications of DNA distinct from those generated through Ler binding. Furthermore, ler expression is a key parameter modulating the variability of the proportions of bacterial subpopulations. Accordingly, modulating the production of Ler into a nonpathogenic E. coli strain reproduces the bimodal expression of LEE 5. Finally, this study illustrates how two nucleoid-binding proteins can reshape the epigenetic regulation of bacterial virulence

Advances in Microbiome-Derived Solutions and Methodologies Are Founding a New Era in Skin Health and Care

The microbiome, as a community of microorganisms and their structural elements, genomes, metabolites/signal molecules, has been shown to play an important role in human health, with significant beneficial applications for gut health. Skin microbiome has emerged as a new field with high potential to develop disruptive solutions to manage skin health and disease. Despite an incomplete toolbox for skin microbiome analyses, much progress has been made towards functional dissection of microbiomes and host-microbiome interactions. A standardized and robust investigation of the skin microbiome is necessary to provide accurate microbial information and set the base for a successful translation of innovations in the dermo-cosmetic field. This review provides an overview of how the landscape of skin microbiome research has evolved from method development (multi-omics/data-based analytical approaches) to the discovery and development of novel microbiome-derived ingredients. Moreover, it provides a summary of the latest findings on interactions between the microbiomes (gut and skin) and skin health/disease. Solutions derived from these two paths are used to develop novel microbiome-based ingredients or solutions acting on skin homeostasis are proposed. The most promising skin and gut-derived microbiome interventional strategies are presented, along with regulatory, safety, industrial, and technical challenges related to a successful translation of these microbiome-based concepts/technologies in the dermo-cosmetic industry

Clipping Could Be the Best Treatment Modality for Recurring Anterior Communicating Artery Aneurysms Treated Endovascularly

The anterior communicating artery (AcoA) is the most common location for intracranial aneurysms. To present occlusion outcomes, complication rate, recurrence rate, and predictors of recurrence in a large cohort with AcoA aneurysms treated primarily with endosaccular embolization. We also attempt to present data on the most effective treatment modality for recurrent AcoA aneurysms. This is a retrospective, single-center study, reviewing the outcomes of 463 AcoA aneurysms treated endovascularly between 2003 and 2018. The study cohort consisted of 463 patients. Adequate immediate occlusion was achieved in 418 (90.3%). Independent functional status at discharge was observed in 269 patients (58.0%), and the mortality rate was 6.8% (31). At 6 months, adequate occlusion was achieved in 418 (90.4%). Of all the patients, recurrence was observed in 101 cases (21.8%), and of those, 98 (22.4%) underwent retreatment. The combined frequency of retreatment for the coiling group was 42.4%, which was significantly higher than the 0 incident of retreatment in the clipping group (P < .0001). Among the retreatment cohort, there was a significantly higher subsequent retreatment rate in the endovascular group (0% in the clipping group vs 42.4% in the endovascular group, P < .0001). Coiling with and without stent/balloon assistance is a relatively safe and effective modality for the treatment of AcoA aneurysms; however, in the setting of recurrence, microsurgical reconstruction leads to improved outcomes regarding durable occlusion, thus avoiding the potential for multiple interventions in the future