Molecular basis for the emergence of a new hospital endemic tigecycline-resistant Enterococcus faecalis ST103 lineage

Autor(es)

Gebieluca Dabul, Andrei Nicoli ^[1] ; Avaca-Crusca, Juliana Sposto ^{[1, 2]} ; Navais, Roberto Barranco ^{[1, 3]} ; Merlo, Thais Panhan ^[1] ; Van Tyne, Daria ^{[4, 5, 6]} ; Gilmore, Michael S. ^{[4, 5]} ; Baratella da Cunha Camargo, Ilana Lopes ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sao Carlos Inst Phys, POB 369, BR-13556097 Sao Carlos, SP - Brazil

^[2] Inst Criminalist Superintendencia Policia Tecn Ci, Nucleo Pericias Criminalist Sao Jose do Rio Preto, Sao Jose Do Rio Preto, SP - Brazil

^[3] Umea Univ, Dept Mol Biol, Umea Ctr Microbial Res, Lab Mol Infect Med Sweden, S-90187 Umea - Sweden

^[4] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA - USA

^[5] Harvard Med Sch, Dept Microbiol & Immunobiol, 25 Shattuck St, Boston, MA - USA

^[6] Univ Pittsburgh, Sch Med, Div Infect Dis, 3550 Terrace St, Pittsburgh, PA - USA

• Tipo de documento: Artigo Científico
• Fonte: INFECTION GENETICS AND EVOLUTION; v. 67, p. 23-32, JAN 2019.
• Citações Web of Science: 1

Resumo

Enterococcus faecalis are a major cause of nosocomial infection worldwide, and the spread of vancomycin resistant strains (VRE) limits treatment options. Tigecycline-resistant VRE began to be isolated from inpatients at a Brazilian hospital within months following the addition of tigecycline to the hospital formulary. This was found to be the result of a spread of an ST103 E. faecalis clone. Our objective was to identify the basis for tigecycline resistance in this lineage. The genomes of two closely related tigecycline-susceptible (MIC = 0.06 mg/L), and three representative tigecycline-resistant (MIC = 1 mg/L) ST103 isolates were sequenced and compared. Further, efforts were undertaken to recapitulate the emergence of resistant strains in vitro. The specific mutations identified in clinical isolates in several cases were within the same genes identified in laboratory-evolved strains. The contribution of various polymorphisms to the resistance phenotype was assessed by trans-complementation of the wild type or mutant alleles, by testing for differences in mRNA abundance, and/or by examining the phenotype of transposon insertion mutants. Among tigecycline-resistant clinical isolates, five genes contained non-synonymous mutations, including two genes known to be related to enterococcal tigecycline resistance (tetM and rpsJ). Finally, within the in vitro-selected resistant variants, mutation in the gene for a MarR-family response regulator was associated with tigecycline resistance. This study shows that E. faecalis mutates to attain tigecycline resistance through the complex interplay of multiple mechanisms, along multiple evolutionary trajectories. (AU)

• Processo FAPESP: 13/24952-0 - Padrões da emergência de enterococci e staphylococci multiresistentes no Brasil e busca por novos fármacos
• Beneficiário: Andrei Nicoli Gebieluca Dabul Dias de Sousa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/14592-1 - Comparação genotípica e fenotípica de Enterococcus faecalis resistentes à vancomicina isolados nos anos de 2009 e 2011 em um hospital de Minas Gerais.
• Beneficiário: Thaís Panhan Merlo
• Modalidade de apoio: Bolsas no Brasil - Mestrado