Evaluation of Quaternary Ammonium Surfactants as prophylactic options for Streptococcus agalactiae infections

• Autor(a) principal: Ferreira, Carolina Borges
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/132855
• topic: Streptococcus agalactiae; group B streptococcus; neonatal infections; intrapartum prophylaxis; antimicrobial resistance; selective pressure assay; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Streptococcus agalactiae is a leading cause of morbidity and mortality in neonates. Vertical trans mission during labor and delivery, is currently prevented by intrapartum antibiotic prophylaxis (IAP). However, resistance to the antibiotics used in IAP has been emerging and increasing. With no vaccine available, it is important to find new alternatives. Previous studies have showed that the cationic surfac tant dodecyl-pyridinium bromide (C12PB) is bactericide against S. agalactiae at concentrations that do not affect the commensal flora and epithelial cells of the vaginal mucosa. To get a step further in vali dating C12PB as a good prophylactic compound, this work aimed to evaluate its ability to induce anti microbial resistance against S. agalactiae. Isogenic clones were continuously propagated without and under C12PB sub-inhibitory concentrations. Phenotypic tests coupled with Whole Genome Sequencing of the populations exposed to such conditions were used to identify the emergence and putative mech anisms of resistance. As a proof-of-concept, the same procedure was performed with erythromycin, an antibiotic used in S. agalactiae intrapartum prophylaxis. In addition, the toxicity and pro-inflammatory potential of C12PB towards epithelial cells were also evaluated by the MTT assay and ELISA, respec tively. Contrarily to erythromycin, where the Minimum Inhibitory Concentration (0.125 µg/ml) doubled after 7 passages and increased up to >2000-times after 56 passages (end point), the appearance of re sistance to C12PB was not observed during the assay, which was also confirmed at the genome level. On the other hand, for erythromycin, genome comparison against the original clone revealed multiple mu tations on ribosome-associated genes (including the 23S rRNA m5U1939 methyltransferase, ribosomal protein L22 and 23S rRNA) associated with resistance acquisition. Additionally, overall toxicity and inflammation were low. In conclusion, together with the previous results, these findings highlight C12PB as a promising candidate for the prevention of S. agalactiae vertical transmitted infections.