RESUMO
Multidrug resistant bacteria have been a worldwide concern for decades. Though new molecules that effectively target Gram-positive bacteria are currently appearing on the market, a gap remains in the treatment of infections caused by Gram-negative bacteria. Therefore, new strategies must be developed against these pathogens. The aim of this study was to select an antibiotic for which a bacterium is naturally resistant and to use an escort molecule to restore susceptibility, similarly to the model of ß-lactam/ ß-lactamase inhibitors. High-content screening was performed on the reference strain PA01, allowing the selection of four polyamino-isoprenic compounds that acted synergistically with doxycycline. They were assayed against clinical isolates and Multi-Drug-Resistant strains. One of these compounds was able to decrease the MIC of doxycycline on the reference strain, efflux pump overproducers and clinical isolates of P. aeruginosa, to the susceptibility level. Similar results were obtained using chloramphenicol as the antibiotic. Membrane permeation assays and real-time efflux experiments were used to characterize the mechanism of doxycycline potentiation. The results showed that the selected compound strongly decreases the efficiency of glucose-triggered efflux associated with a slight destabilization of the outer membrane. According to these data, targeting natural resistance may become an interesting way to combat MDR pathogens and could represent an alternative to already devised strategies.
Assuntos
Cloranfenicol/farmacologia , Doxiciclina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Relação Dose-Resposta a Droga , Técnicas In Vitro , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Since cholera appeared in Africa during the 1970s, cases have been reported on the continent every year. In Sub-Saharan Africa, cholera outbreaks primarily cluster at certain hotspots including the African Great Lakes Region and West Africa. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we applied MLVA (Multi-Locus Variable Number Tandem Repeat Analysis) typing of 337 Vibrio cholerae isolates from recent cholera epidemics in the Democratic Republic of the Congo (DRC), Zambia, Guinea and Togo. We aimed to assess the relationship between outbreaks. Applying this method, we identified 89 unique MLVA haplotypes across our isolate collection. MLVA typing revealed the short-term divergence and microevolution of these Vibrio cholerae populations to provide insight into the dynamics of cholera outbreaks in each country. Our analyses also revealed strong geographical clustering. Isolates from the African Great Lakes Region (DRC and Zambia) formed a closely related group, while West African isolates (Togo and Guinea) constituted a separate cluster. At a country-level scale our analyses revealed several distinct MLVA groups, most notably DRC 2011/2012, DRC 2009, Zambia 2012 and Guinea 2012. We also found that certain MLVA types collected in the DRC persisted in the country for several years, occasionally giving rise to expansive epidemics. Finally, we found that the six environmental isolates in our panel were unrelated to the epidemic isolates. CONCLUSIONS/SIGNIFICANCE: To effectively combat the disease, it is critical to understand the mechanisms of cholera emergence and diffusion in a region-specific manner. Overall, these findings demonstrate the relationship between distinct epidemics in West Africa and the African Great Lakes Region. This study also highlights the importance of monitoring and analyzing Vibrio cholerae isolates.
Assuntos
Cólera/epidemiologia , Cólera/microbiologia , Epidemias/história , Evolução Molecular , Haplótipos/genética , Vibrio cholerae/genética , África Subsaariana/epidemiologia , Análise por Conglomerados , Primers do DNA/genética , Frequência do Gene , Genética Populacional , História do Século XX , História do Século XXI , Humanos , Repetições Minissatélites/genética , Filogenia , Filogeografia , Reação em Cadeia da PolimeraseRESUMO
We analyzed 1,093 Vibrio cholerae isolates from the Democratic Republic of the Congo during 1997-2012 and found increasing antimicrobial drug resistance over time. Our study also demonstrated that the 2011-2012 epidemic was caused by an El Tor variant clonal complex with a single antimicrobial drug susceptibility profile.
Assuntos
Antibacterianos/farmacologia , Cólera/epidemiologia , Cólera/microbiologia , Farmacorresistência Bacteriana , Vibrio cholerae/efeitos dos fármacos , Cólera/tratamento farmacológico , Cólera/história , República Democrática do Congo/epidemiologia , Surtos de Doenças , Geografia , História do Século XX , História do Século XXI , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Filogenia , Vibrio cholerae/classificação , Vibrio cholerae/genéticaRESUMO
Anemia is the most common pathology encountered in hematology. Etiologies are numerous, so it is important to adopt a rigorous approach. Complementary examinations must be specific to the clinical situation in order to determine the mechanisms on the one hand and decide the therapeutic management on the other. We report the observation of a case of sudden onset of profound pancytopenia. Investigation led to the diagnosis of major folic acid deficiency with favorable evolution. Through this case, we describe the diagnostic approach towards anemia and the mechanisms involved in the formation of folate deficiency.
