Seasonal and Regional Dynamics of M. ulcerans Transmission in Environmental Context: Deciphering the Role of Water Bugs as Hosts and Vectors

Buruli ulcer, caused by Mycobacterium ulcerans, is a devastating skin disease. Most cases of Buruli ulcer occur in poor rural communities. As a result, treatment is frequently sought too late and about 25% of those infected—particularly children—become permanently disabled. Outbreaks of Buruli ulcer have always been associated with swampy areas. However, the route(s) of bacillus transmission is (are) still unclear. This Mycobacterium species resides in water where it colonizes many ecological niches such as aquatic plants, herbivorous animals and predatory/carnivorous insects. For several years the role of water bugs as hosts and vectors of M. ulcerans was suspected and was demonstrated under laboratory conditions. The aim of this work was to further assess the role of water bugs as hosts and vectors of M. ulcerans in environmental context. This work identifies several water bug families as hosts of M. ulcerans in Buruli ulcer endemic area. The detection of bacilli in saliva of human biting insects provides further evidence for their role in M. ulcerans transmission. Interestingly, three of these insects are good flyers, and as such could participate in M. ulcerans dissemination

A comparison of different strategies for antimicrobial peptides incorporation onto/into lipid nanocapsules

International audienceAim: Over the last decade, antimicrobial peptides (AMPs) have emerged as a promising alternative for the treatment of various infections. The aim of this work is to explore the potential of lipid nanocapsules for the delivery of AMPs. Three approaches were compared in terms of encapsulation efficiency, peptide activity and protection against proteases: peptide encapsulation, surface adsorption or covalent attachment of three selected AMPs. Results: A potentiation of the antimicrobial activity and a partial protection of the peptides after adsorption were demonstrated compared with native peptides. Conversely, encapsulation allowed better peptide stability, correlated with higher encapsulation efficiencies and a preservation of the activity. Finally, the covalent attachment strategy turned out to be less conclusive due to peptide inactivation. Conclusion: In brief, a lipid nanocapsule-based platform appears suitable to deliver AMPs

Synergistic Effect of Combinations Containing EDTA and the Antimicrobial Peptide AA230, an Arenicin-3 Derivative, on Gram-Negative Bacteria

International audienceThe worldwide occurrence of resistance to standard antibiotics and lack of new antibacterial drugs demand new strategies to treat complicated infections. Hence, the aim of this study was to examine the antibacterial activities of an antimicrobial peptide, arenicin-3 derivative AA230, and ethylenediaminetetraacetic acid (EDTA) as well as the two compounds in combination against Gram-negative bacteria. AA230 showed strong antibacterial activity against all of the studied standard strains and clinical isolates, with minimum inhibitory concentrations ranging between 1 µg/mL and 8 µg/mL. AA230 exhibited a bactericidal mode of action. EDTA inhibited the growth of Acinetobacter baumannii at 500-1000 µg/mL. Strains of Acinetobacter baumannii were found to be more susceptible to EDTA than Pseudomonas aeruginosa or Escherichia coli. The antibacterial effects of both AA230 and EDTA were independent of the antibiotic resistance patterns. Indifference to synergistic activity was observed for AA230 and EDTA combinations using checkerboard titration. In time-kill studies, a substantial synergistic interaction between AA230 and EDTA was detected against all of the tested strains. The addition of EDTA enabled a 2-4-fold decrease in the AA230 dose. In conclusion, AA230 could have potential applications in the treatment of infections caused by Gram-negative organisms, and its effect can be potentiated by EDTA

Colistin–glycopeptide combinations against multidrug-resistant Acinetobacter baumannii in a mouse model of pneumonia

International audienceAim: To assess the effect of colistin-glycopeptide combination against a multidrug-resistant strain of Acinetobacter baumannii. Materials & methods: We used in vitro procedures (Etest method, checkerboard test and kill-time assays) and a mouse model of a carbapenem-resistant A. baumannii pneumonia. Results: The colistin-teicoplanin combination allowed a 74% increase of the survival in the mouse model within the 4 days following bacterial inoculation as compared with saline or colistin alone (p = 0.06). Concurrently, the colistin-vancomycin combination presented a similar efficacy as compared with saline or colistin alone in the mouse model. Conclusion: According to those preliminary results, using the colistin-teicoplanin combination in therapeutic deadlocks encountered in certain multiresistant A. baumannii pneumonia could be envisaged if the results are confirmed

Antibacterial action of lipid nanocapsules containing fatty acids or monoglycerides as co-surfactants.

International audienceLipid nanocapsules (LNCs) are a new generation of biomimetic nanocarriers obtained via a phase inversion temperature method and have an oily core of medium-chain triglycerides that is surrounded by a shelf containing a lipophilic surfactant (lecithin) and a hydrophilic surfactant macrogol 15-hydroxystearate. The aim of the present study was to produce LNCs with antibacterial activity by replacing lecithin with other lipophilic surface active compounds, namely medium-chain fatty acids and their 1-monoglycerides, which are known to have antimicrobial properties. Fatty acids and monoglycerides were found to affect the properties of LNCs, such as particle size and zeta potential. Incorporation of a co-surfactant decreased significantly particle size (p⩽0.0039). Furthermore, incorporation of either lecithin or fatty acids with at least 10 carbon atoms yielded LNCs with the zeta potential significantly more negative than that of LNCs composed solely of triglycerides and macrogol 15 hydroxystearate (p⩽0.0310). Moreover, they were capable of decreasing the phase inversion temperature. The activity of the LCNs against Gram-positive S. aureus, including a methicillin-resistant strain, increased with increases in the length of the hydrocarbon tail. Monoglyceride-LNCs were found to be more active than the corresponding fatty acids. The opposite behaviour was observed for Gram-negative bacteria, whereby only caproic acid- and caprylic acid-LNCs were found to be active against these organisms. The monoglyceride-LNCs were bactericidal, and they killed in a time-dependent manner. Fatty acid-LNCs killed in a concentration-dependent manner. A haemolysis assay was performed to obtain preliminary information on the safety of the tested LNCs. In the case of fatty acid-LNCs, the concentrations at which bacterial growth was inhibited were similar to the haemolytic concentrations. However, monoglyceride-LNCs showed antibacterial action at concentrations much lower than those at which haemolysis was observed. In conclusion, monoglyceride-LNCs are promising candidates as carriers for the encapsulation of antibacterial agents, particularly against S. aureus.</p

Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity.

Bacterial antibiotic resistance is an emerging public health problem worldwide; therefore, new therapeutic strategies are needed. Many studies have described antipsychotic compounds that present antibacterial activity. Hence, the aims of this study were to evaluate the in vitro antibacterial activity of antipsychotics belonging to different chemical families, to assess the influence of their association with lipid nanocapsules (LNCs) on their antimicrobial activity as well as drug release and to study the uptake of LNCs by bacterial cells. Antibacterial activity was evaluated against Gram-positive Staphylococcus aureus and Gram negative Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by minimum inhibitory concentration (MIC) assay, and the capability of killing tested microorganisms was evaluated by time kill assay. LNCs were prepared by phase inversion method, and the antipsychotic agents were incorporated using pre-loading and post-loading strategies. Only phenothiazines and thioxanthenes showed antibacterial activity, which was independent of antibiotic-resistance patterns. Loading the nanocarriers with the drugs affected the properties of the former, particularly their zeta potential. The release rate depended on the drug and its concentration-a maximum of released drug of less than 40% over 24 hours was observed for promazine. The influence of the drug associations on the antibacterial properties was concentration-dependent since, at low concentrations (high nanocarrier/drug ratio), the activity was lost, probably due to the high affinity of the drug to nanocarriers and slow release rate, whereas at higher concentrations, the activity was well maintained for the majority of the drugs. Chlorpromazine and thioridazine increased the uptake of the LNCs by bacteria compared with blank LNCs, even below the minimum inhibitory concentration

Dynamic population of water bugs in a Buruli ulcer endemic area and their rate of colonization by M. ulcerans

Date du colloque&nbsp;: 04/2009</p

Iterative fecal microbiota transplantations for eradicating digestive colonization with carbapenemase-producing Enterobacteriaceae: is it worth it?

International audienceCarbapenemase-producing Enterobacteriaceae (CPE) have emerged as a major source of bacterial resistance and their dissemination is a serious public health threat.1 It has also been demonstrated that those bacteria could disseminate outside the hospital setting. A large study including 34 hospitals in Spain demonstrated that a significant proportion of patients identified as colonized or infected with CPE during hospitalization probably acquired this multi-resistant organism in a nursing home during the period preceding their hospital admission.2 In addition, a recent review of the literature demonstrated that according to US-based studies, the percentage of CPE isolates that could be associated with the community ranged from 5.6 to 10.8%.

Antifungal and Antibacterial Metabolites from a French Poplar Type Propolis

During this study, the in vitro antifungal and antibacterial activities of different extracts (aqueous and organic) obtained from a French propolis batch were evaluated. Antifungal activity was evaluated by broth microdilution on three pathogenic strains: Candida albicans, C. glabrata, and Aspergillus fumigatus. Antibacterial activity was assayed using agar dilution method on 36 Gram-negative and Gram-positive strains including Staphylococcus aureus. Organic extracts showed a significant antifungal activity against C. albicans and C. glabrata (MIC80 between 16 and 31 µg/mL) but only a weak activity towards A. fumigatus (MIC80 = 250 µg/mL). DCM based extracts exhibited a selective Gram-positive antibacterial activity, especially against S. aureus (SA) and several of its methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains (MIC100 30–97 µg/mL). A new and active derivative of catechin was also identified whereas a synergistic antimicrobial effect was noticed during this study