IHMT

Instituto de Higiene e Medicina Tropical

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2012

Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections.

Thioridazine (TDZ) in combination with antibiotics to which extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) is initially resistant yields a cure. This is due to the fact that TDZ enhances the killing of intracellular M. tuberculosis by non-killing macrophages, inhibits the genetic expression of efflux pumps of M. tuberculosis that extrude antibiotics prior to reaching their intended targets, and inhibits the activity of existing efflux pumps that contribute to the multidrug-resistant phenotype of M. tuberculosis.
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Thioridazine: an old neuroleptic effective against totally drug resistant tuberculosis

Globally, tuberculosis infections continue to increase their resistance to antibiotics. Multidrug resistant tuberculosis infections (MDR TB) have progressed to extensively drug resistance status (XDR TB) and the latter have evolved in some parts of the world to totally drug resistant (TDR TB) infections.
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Enhancement of commercial antifungal agents by Kojic Acid.

Natural compounds that pose no significant medical or environmental side effects are potential sources of antifungal agents, either in their nascent form or as structural backbones for more effective derivatives. Kojic acid (KA) is one such compound. It is a natural by-product of fungal fermentation commonly employed by food and cosmetic industries.
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Antimony resistance and environment: Elusive links to explore during Leishmania life cycle.

Leishmania drug resistance and particularly antimony resistance still continues to emerge in different part of the world. Because visceral and cutaneous leishmaniasis are transmitted in foci with zoonotic or anthroponotic life-cycles, the link between chemotherapeutic resistance and the selection for drug resistance, through drug consumption, cannot be as obvious for all forms of leishmaniasis.
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Microsporidia as emerging pathogens and the implication for public health: a 10-year study on HIV-positive and -negative patients.

Despite recent advances in the understanding and diagnosis of emerging microsporidian pathogens, more research is necessary to elucidate their complex epidemiology. In fact, studies that reflect true human-infecting microsporidian prevalence are still inadequate. The present 10-year study was undertaken to examine the occurrence of Microsporidia in 1989 stools, 69 urine and 200 pulmonary specimens from HIV-positive and HIV-negative patients using PCR and DNA sequencing.
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Functional genomics studies of Rhipicephalus (Boophilus) annulatus ticks in response to infection with the cattle protozoan parasite, Babesia bigemina.

Ticks are obligate haematophagous ectoparasites of wild and domestic animals as well as humans, considered to be second worldwide to mosquitoes as vectors of human diseases, but the most important vectors of disease-causing pathogens in domestic and wild animals. Babesia spp. are tick-borne pathogens that cause a disease called babesiosis in a wide range of animals and in humans.
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CpG-containing oligodeoxynucleotides increases resistance of Anopheles mosquitoes to Plasmodium infection.

Unmethylated CpG dinucleotide motifs in bacterial DNA or in synthetic oligodeoxynucleotides (ODN) are potent stimulators of the vertebrate innate immune system. However, the potential of these DNA species to modulate mosquito immunity have not been explored. In the present study, we investigated the effects of CpG-ODN on the outcome of Plasmodium infection in insects and on the modulation of mosquito immunity to Plasmodium.
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GB virus C (GBV-C) evolutionary patterns revealed by analyses of reference genomes, E2 and NS5B sequences amplified from viral strains circulating in the Lisbon area (Portugal).

GBV-C is a non-pathogenic virus that is largely dispersed in different human populations. The phylogenetic analysis of the 5′-untranslated region (5’UTR) of the GBV-C genome has led to the segregation of viral strains into six genotypes, but incongruent results are frequently obtained depending on the genome region analyzed. In this report, different phylogenetic approaches and multivariate statistics were combined to disclose evolutionary patterns that contribute to shape GBV-C evolution.
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Phylodynamics of the HIV-1 CRF02_AG clade in Cameroon.

Evolutionary analyses have revealed an origin of pandemic HIV-1 group M in the Congo River basin in the first part of the XX century, but the patterns of historical viral spread in or around its epicentre remain largely unexplored. Here, we combine epidemiologic and molecular sequence data to investigate the spatiotemporal patterns of the CRF02_AG clade.
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Inhibition of quorum sensing and efflux pump system by trifluoromethyl ketone proton pump inhibitors.

BACKGROUND:
One major microbiological problem is the widespread antibiotic resistance. There is an urgent need for new antibiotics and ways to treat multi-drug-resistant infections. Inhibition of bacterial quorum sensing (QS) systems could be an effective alternative in a smuch as they regulate a broad spectrum of cell functions, including, virulence factor production, biofilm organisation and motility. Influx and efflux bacterial systems involved in quorum sensing (QS) are known to depend on the proton motive force (PMF). Thus, a new series of 12 trifluoromethyl ketones (TFs) known to inhibit the PMF, was investigated for effects on the efflux pump of a QS responding bacterium, for its subsequent effect on the response to a QS signal and its direct inhibition of the response to a QS signal.
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