Natural extracts stimulate membrane-associated mechanisms of resistance in Gram-negative bacteria.

UNLABELLED: Several mechanisms are involved in the bacterial resistance towards antimicrobial agents. The membrane-associated mechanisms of resistance were studied in Escherichia coli strains after incubation with Thymus maroccanus essential oil, its major components (carvacrol and thymol) or with certain antibiotics. The minimum inhibitory concentration (MIC) and the expression of membrane proteins, porins and efflux pumps were determined in wild type and derivative strains. Derivative strains adapted to different compounds displayed a high level of resistance to all tested antibiotics. The MIC increase is associated with an overexpression of an efflux pump immunorelated to AcrAB-TolC in various variants. Interestingly, the expression of outer membrane proteins slightly decreases in these strains. We demonstrate that the increase in antibiotic resistance correlates with membrane changes observed in the variants. This type of bacterial adaptation to natural compounds can occur in vivo providing the emergence/selection of bacteria less susceptible to clinically used antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Thymus maroccanus essential oil and some major components are able to select variants that modify the expression of transporters involved in the influx (porins) and in the efflux (AcrAB family) of various drugs. Importantly, these membrane proteins are involved in the transport of natural compounds and several antibiotic families. This special 'membrane adaptation' can explain the persistence of less susceptible/tolerant bacteria in the environment where natural compounds are present and the continuous stimulation of efflux systems in these bacteria.

Thymus maroccanus essential oil, a membranotropic compound active on Gram-negative bacteria and resistant isolates.

AIMS: The effects of Thymus maroccanus essential oil (EO) on the integrity of the cell membranes and the permeability of the outer membrane (OM) and inner membrane (IM) of Escherichia coli, Enterobacter aerogenes and Salmonella enterica Typhimurium were investigated. METHODS AND RESULTS: The bacterial release of intracellular proteins, cytoplasmic ß-galactosidase and periplasmic ß-lactamase induced by T. maroccanus EO was compared to the membranotropic activity of polymyxin B (PB) known as an effective permeabilizer of the membrane of Gram-negative bacteria. Results showed that T. maroccanus EO increased the permeability of the OM and IM of studied bacteria and induced the release of intracellular proteins into the external medium. CONCLUSIONS: The effect of T. maroccanus EO on the outer membrane was comparable to that of PB, and both T. maroccanus EO and PB induce similar levels of ß-lactamase release. In addition, it also promoted the release of the cytoplasmic ß-galactosidase. Moreover, the lipopolysaccharide molecules and the overexpression of efflux pumps seem to play a crucial role in the level of susceptibility of studied bacteria to the permeabilizing effect of T. maroccanus EO. SIGNIFICANCE AND IMPACT OF STUDY: These results demonstrate that T. maroccanus EO can restore antibiotic activity by targeting the two bacterial membranes and would be attractive candidates for developing new adjuvants for combating resistant Gram-negative bacteria.

Rare Presentation of a Rare Disease (Erdheim-Chester disease): A Case Report.

ABSTRACT: Erdheim-Chester disease (ECD) was first reported by J. Erdheim and W. Chester, in 1930. There are less than 250 reported cases till date. We report a case of ECD in a 16- year-old Malay male, who initially presented with elusive anemic symptoms with more specific symptoms of bony pain, cardiorespiratory and hepatic involvement evolving as the disease progressed. KEY WORDS: Erdheim-Chester disease.

Anticandidal activity of the essential oils of Thymus maroccanus and Thymus broussonetii and their synergism with amphotericin B and fluconazol.

The discovery of antifungal drugs had eradicated some infections that ravaged the humankind. But their indiscriminate use has led to the development of multidrug resistant pathogens. One strategy employed to overcome these resistance mechanisms is the use of combination of the essential oils (EOs) of medicinal plants and conventional drugs. In this study, we investigated a possible synergistic effect of the EOs of two Moroccan endemic thymes (Thymus broussonetii and T. maroccanus) with amphotericin B (Amp B) and fluconazol against Candida albicans. The fractional inhibitory concentration indices (FICI) of T. maroccanus and T. broussonetii EOs combined with Amp B and fluconazol, calculated from the checkerboard titer assay, were 0.49, 0.27, 0.37 and 0.3, respectively. Also, our results indicate that the synergistic effect of EOs with fluconazol was stronger than the combination with Amp B. All these data highlight that the EOs tested potentiate the antifungal action of Amp B and fluconazol, suggesting a possible utilization of these EOs in addition to antifungal drugs for the treatment of some candidiasis due to C. albicans. The use of these combinations is likely to reduce the minimum effective dose of the drugs, thus minimizing their toxic side effects and the treatment cost.

[Metastatic and hemorrhagic brain arteriovenous fistulae due to a choriocarcinoma. Case report]. / Fistule artérioveineuse cérébrale métastatique hémorragique d'origine choriocarcinomateuse.

Brain metastasis of choriocarinoma is uncommon. These tumors develop in women of childbearing age and commonly produce signs and symptoms of subarachnoid hemorrhage, intracerebral hemorrhage, or brain tumor. Diagnosis can be established by histologic study of operative swabs and bioassay of the patient's blood, urine and cerebrospinal fluid for chorionic gonadotropin. This condition is highly chemo- and radiosensitive. We report the case of a 36-year-old woman with intracranial neoplastic fistulae. Rupture occurred 3 days after spontaneous abortion at 3 months of pregnancy. The patient presented with hemiplegia, aphasia and unclear consciousness. Left fronto-parietal hematoma was diagnosed on the CT scan, and cerebral angiography showed an arteriovenous intracranial fistulae. The hematoma and angioma were surgically removed successfully. The histological examination showed a metastatic choriocarcinoma. Surgery was followed by chemotherapy and radiotherapy. After 6 years of follow-up, complete remission has been obtained.

Novel meroterpenoids from Cystoseira mediterranea: use of the crown-gall bioassay as a primary screen for lipophilic antineoplastic agents.

Using a slight modification of the crown-gall potato disc bioassay, we were able to apply this test for two previously described antineoplastic lipophilic metabolites, didemnin B and mediterraneol A [1], and to use it as a guide for chromatographic separations of meroterpenoids from Cystoseira mediterranea. An active compound, mediterraneone [3], was isolated, and its structure was found to be a novel norsesquiterpenoid by chemical and spectral methods.