Differences in Cystic Fibrosis-Associated Burkholderia spp. Bacteria Metabolomes after Exposure to the Antibiotic Trimethoprim

Autor(es)

McAvoy, Andrew C. ^[1] ; Jaiyesimi, Olakunle ^[1] ; Threatt, Paxton H. ^[1] ; Seladi, Tyler ^[1] ; Goldberg, Joanna B. ^{[2, 3]} ; da Silva, Ricardo R. ^[4] ; Garg, Neha ^{[5, 6, 2]}

Afiliação do(s) autor(es)

^[1] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 - USA

^[2] Emory Univ, Dept Pediat, Div Pulmonol Allergy Immunol Cyst Fibrosis & Slee, Sch Med, Atlanta, GA 30322 - USA

^[3] Emory Childrens Cyst Fibrosis Ctr, Atlanta, GA 30322 - USA

^[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[5] Georgia Inst Technol, Sch Chem & Biochem, Sch Biol Sci, Ctr Microbial Dynam & Infect, Atlanta, GA 30332 - USA

^[6] Georgia Inst Technol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 - USA

• Tipo de documento: Artigo Científico
• Fonte: ACS INFECTIOUS DISEASES; v. 6, n. 5, p. 1154-1168, MAY 8 2020.
• Citações Web of Science: 0

Resumo

The Burkholderia cepacia complex is a group of closely related bacterial species with large genomes that infect immunocompromised individuals and those living with cystic fibrosis. Some of these species are found more frequently and cause more severe disease than others, yet metabolomic differences between these have not been described. Furthermore, our understanding of how these species respond to antibiotics is limited. We investigated the metabolomics differences between three most prevalent Burkholderia spp. associated with cystic fibrosis: B. cenocepacia, B. multivorans, and B. dolosa in the presence and absence of the antibiotic trimethoprim. Using a combination of supervised and unsupervised metabolomics data visualization and analysis tools, we describe the overall differences between strains of the same species and between species. Specifically, we report, for the first time, the role of the pyomelanin pathway in the metabolism of trimethoprim. We also report differences in the detection of known secondary metabolites such as fragin, ornibactin, and N-acylhomoserine lactones and their analogs in closely related strains. Furthermore, we highlight the potential for the discovery of new secondary metabolites in clinical strains of Burkholderia spp. The metabolomics differences described in this study highlight the personalized nature of closely related Burkholderia strains. (AU)

• Processo FAPESP: 17/18922-2 - Desenvolvimento de uma plataforma computacional modular extensível para análises de experimentos de metabolômica e metagenômica: inovando com a descoberta de novas atividades enzimáticas e produtos naturais de interesse farmacêutico derivados
• Beneficiário: Ricardo Roberto da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Jovens Pesquisadores
• Processo FAPESP: 19/05026-4 - Desenvolvimento de uma plataforma computacional modular extensível para análises de experimentos de metabolômica e metagenômica: Inovando com a descoberta de novas atividades enzimáticas e produtos naturais de interesse farmacêutico derivados
• Beneficiário: Ricardo Roberto da Silva
• Modalidade de apoio: Bolsas no Brasil - Programa BIOTA - Jovens Pesquisadores