Ana Paula Marchi1,2, Lauro Vieira Perdigão Neto3,4,5, Marina Farrel Côrtes3,4, Victor Augusto Camarinha de Castro Lima3,4, Roberta Cristina Ruedas Martins4, Lucas Augusto Moyses Franco3,6, Flavia Rossi7, Vanderson Rocha8, Anna S Levin3,4,5, Silvia Figueiredo Costa3,4,5. 1. Departamento de Moléstias Infecciosas E Parasitárias, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, São Paulo, 01246-903, Brazil. marchi.ap@gmail.com. 2. Laboratório de Investigação Médica LIM 49, Bacteriologia E Resistência Antimicrobiana, Instituto de Medicina Tropical da FMUSP, Av. Dr. Enéas Carvalho de Aguiar, 470, São Paulo, 05403-000, Brazil. marchi.ap@gmail.com. 3. Departamento de Moléstias Infecciosas E Parasitárias, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, São Paulo, 01246-903, Brazil. 4. Laboratório de Investigação Médica LIM 49, Bacteriologia E Resistência Antimicrobiana, Instituto de Medicina Tropical da FMUSP, Av. Dr. Enéas Carvalho de Aguiar, 470, São Paulo, 05403-000, Brazil. 5. Departamento de Controle de Infecção, Hospital das Clínicas da Universidade de São Paulo, Rua Dr. Ovídio Pires de Campos 225, Sala 629, São Paulo, 05403-010, Brazil. 6. Laboratório de Investigação Médica LIM46, Parasitologia, Instituto de Medicina Tropical da FMUSP, Av. Dr. Enéas Carvalho de Aguiar, 470, São Paulo, 05403-000, Brazil. 7. Sessão de Microbiologia, Divisão de Laboratório de Laboratório Central, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155, São Paulo, 05403-010, Brazil. 8. Departamento de Hematologia, Hemoterapia E Terapia Celular, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155, São Paulo, 05403-010, Brazil.
Abstract
BACKGROUND: Vancomycin-resistant Enterococcus faecium (VREfm) is an important agent of hospital-acquired infection. VanA phenotype is characterized by resistance to high levels of vancomycin and teicoplanin and is encoded by the vanA gene, whereas VanD phenotype is characterized by resistance to vancomycin and susceptibility or intermediate resistance to teicoplanin; however, some isolates carry a VanD phenotype with a vanA genotype, but there are many gaps in the knowledge about the genetic mechanisms behind this pattern. OBJECTIVE: To characterize the genetic structure, clonality, and mobile genetic elements of VRE isolates that display a VanD-vanA phenotype. RESULTS: All vanA VRE-fm isolates displayed minimum inhibitory concentration (MIC) for vancomycin > 32µg/mL and intermediate or susceptible MIC range for teicoplanin (8-16µg/mL). The isolates were not clonal, and whole-genome sequencing analysis showed that they belonged to five different STs (ST478, ST412, ST792, ST896, and ST1393). The absence of some van complex genes were observed in three isolates: Ef5 lacked vanY and vanZ, Ef2 lacked vanY, and Ef9 lacked orf1 and orf2; moreover, another three isolates had inverted positions of orf1, orf2, vanR, and vanS genes. IS1542 was observed in all isolates, whereas IS1216 in only five. Moreover, presence of other hypothetical protein-encoding genes located downstream the vanZ gene were observed in six isolates. CONCLUSION: VRE isolates can display some phenotypes associated to vanA genotype, including VanA and VanB, as well as VanD; however, further studies are needed to understand the exact role of genetic variability, rearrangement of the transposon Tn1546, and presence of insertion elements in isolates with this profile.
BACKGROUND: Vancomycin-resistant Enterococcus faecium (VREfm) is an important agent of hospital-acquired infection. VanA phenotype is characterized by resistance to high levels of vancomycin and teicoplanin and is encoded by the vanA gene, whereas VanD phenotype is characterized by resistance to vancomycin and susceptibility or intermediate resistance to teicoplanin; however, some isolates carry a VanD phenotype with a vanA genotype, but there are many gaps in the knowledge about the genetic mechanisms behind this pattern. OBJECTIVE: To characterize the genetic structure, clonality, and mobile genetic elements of VRE isolates that display a VanD-vanA phenotype. RESULTS: All vanA VRE-fm isolates displayed minimum inhibitory concentration (MIC) for vancomycin > 32µg/mL and intermediate or susceptible MIC range for teicoplanin (8-16µg/mL). The isolates were not clonal, and whole-genome sequencing analysis showed that they belonged to five different STs (ST478, ST412, ST792, ST896, and ST1393). The absence of some van complex genes were observed in three isolates: Ef5 lacked vanY and vanZ, Ef2 lacked vanY, and Ef9 lacked orf1 and orf2; moreover, another three isolates had inverted positions of orf1, orf2, vanR, and vanS genes. IS1542 was observed in all isolates, whereas IS1216 in only five. Moreover, presence of other hypothetical protein-encoding genes located downstream the vanZ gene were observed in six isolates. CONCLUSION: VRE isolates can display some phenotypes associated to vanA genotype, including VanA and VanB, as well as VanD; however, further studies are needed to understand the exact role of genetic variability, rearrangement of the transposon Tn1546, and presence of insertion elements in isolates with this profile.
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