RESUMO
We report a case of resistance development toward cefiderocol in a patient with intra-abdominal and bloodstream infections caused by carbapenemase-producing Enterobacter cloacae within 21 days of cefiderocol therapy. Whole genome sequencing revealed heterogeneous mutations in the cirA gene, encoding a catecholate siderophore receptor, conferring phenotypic resistance to cefiderocol.
Assuntos
Enterobacter cloacae , Sideróforos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Cefalosporinas , Enterobacter cloacae/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação , Sideróforos/uso terapêutico , beta-Lactamases/genética , CefiderocolRESUMO
Nature offered mankind the first golden era of discovery of novel antimicrobials based on the ability of eukaryotes or micro-organisms to produce such compounds. The microbial world proved to be a huge reservoir of such antimicrobial compounds which play important functional roles in every environment. However, most of those organisms are still uncultivable in a classical way, and therefore, the use of extended culture or DNA based methods (metagenomics) to discover novel compounds promises usefulness. In the past decades, the advances in next-generation sequencing and bioinformatics revealed the enormous diversity of the microbial worlds and the functional repertoire available for studies. Thus, data-mining becomes of particular interest in the context of the increased need for new antibiotics due to antimicrobial resistance and the rush in antimicrobial discovery. In this review, an overview of principles will be presented to discover new natural compounds from the microbiome. We describe culture-based and culture-independent (metagenomic) approaches that have been developed to identify new antimicrobials and the input of those methods in the field as well as their limitations.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Microbiota/genética , Biologia Computacional , Avaliação Pré-Clínica de Medicamentos , Resistência Microbiana a Medicamentos , Regulação Bacteriana da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metagenômica , Família Multigênica/genéticaRESUMO
Thirty-two honeybee (Apis mellifera) colonies were studied in order to detect and measure potential in vivo effects of neonicotinoid pesticides used in cornfields (Zea mays spp) on honeybee health. Honeybee colonies were randomly split on four different agricultural cornfield areas located near Quebec City, Canada. Two locations contained cornfields treated with a seed-coated systemic neonicotinoid insecticide while the two others were organic cornfields used as control treatments. Hives were extensively monitored for their performance and health traits over a period of two years. Honeybee viruses (brood queen cell virus BQCV, deformed wing virus DWV, and Israeli acute paralysis virus IAPV) and the brain specific expression of a biomarker of host physiological stress, the Acetylcholinesterase gene AChE, were investigated using RT-qPCR. Liquid chromatography-mass spectrometry (LC-MS) was performed to detect pesticide residues in adult bees, honey, pollen, and corn flowers collected from the studied hives in each location. In addition, general hive conditions were assessed by monitoring colony weight and brood development. Neonicotinoids were only identified in corn flowers at low concentrations. However, honeybee colonies located in neonicotinoid treated cornfields expressed significantly higher pathogen infection than those located in untreated cornfields. AChE levels showed elevated levels among honeybees that collected corn pollen from treated fields. Positive correlations were recorded between pathogens and the treated locations. Our data suggests that neonicotinoids indirectly weaken honeybee health by inducing physiological stress and increasing pathogen loads.