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1.
Microbiol Spectr ; 9(3): e0105821, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34908468

RESUMO

The Gram-positive pathogen group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections, preterm birth, and stillbirth. Although maternal GBS vaginal colonization is a risk factor for GBS-associated adverse birth outcomes, mechanisms promoting GBS vaginal persistence are not fully defined. GBS possesses a broadly conserved small molecule, CAMP factor, that is co-hemolytic in the presence of Staphylococcus aureus sphingomyelinase C. While this co-hemolytic reaction is commonly used by clinical laboratories to identify GBS, the contribution of CAMP factor to GBS vaginal persistence is unknown. Using in vitro biofilm, adherence and invasion assays with immortalized human vaginal epithelial VK2 cells, and a mouse model of GBS vaginal colonization, we tested the contribution of CAMP factor using GBS strain COH1 and its isogenic CAMP-deficient mutant (Δcfb). We found no evidence for CAMP factor involvement in GBS biofilm formation, or adherence, invasion, or cytotoxicity toward VK2 cells in the presence or absence of S. aureus. Additionally, there was no difference in vaginal burdens or persistence between COH1 and Δcfb strains in a murine colonization model. In summary, our results using in vitro human cell lines and murine models do not support a critical role for CAMP factor in promoting GBS vaginal colonization. IMPORTANCE Group B Streptococcus (GBS) remains a pervasive pathogen for pregnant women and their newborns. Maternal screening and intrapartum antibiotic prophylaxis to GBS-positive mothers have reduced, but not eliminated GBS neonatal disease, and have not impacted GBS-associated preterm birth or stillbirth. Additionally, this antibiotic exposure is associated with adverse effects on the maternal and neonatal microbiota. Identifying key GBS factors important for maternal vaginal colonization will foster development of more targeted, alternative therapies to antibiotic treatment. Here, we investigate the contribution of a broadly conserved GBS determinant, CAMP factor, to GBS vaginal colonization and find that CAMP factor is unlikely to be a biological target to control maternal GBS colonization.


Assuntos
Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Proteínas Hemolisinas/metabolismo , Mucosa/microbiologia , Streptococcus agalactiae/metabolismo , Vagina/microbiologia , Animais , Aderência Bacteriana/fisiologia , Proteínas de Bactérias/genética , Toxinas Bacterianas/metabolismo , Linhagem Celular , Células Epiteliais/microbiologia , Feminino , Deleção de Genes , Proteínas Hemolisinas/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Esfingomielina Fosfodiesterase/metabolismo , Streptococcus agalactiae/genética , Streptococcus agalactiae/crescimento & desenvolvimento
2.
Urol Oncol ; 38(7): 615-621, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32414567

RESUMO

OBJECTIVES: The human microbiome has been linked to the development of several malignancies, but there is scarcity of data on the microbiome of bladder cancer patients. In this study, we analyzed microbial composition and diversity among patients with and without bladder cancer. MATERIAL AND METHODS: Samples were collected from 38 urothelial carcinoma (UC) patients and 10 noncancer controls from August 2018 to May 2019. DNA was extracted and processed for 16 S ribosomal RNA sequencing. Alpha diversity community characteristics including evenness and richness as well as beta diversity metrics were obtained. Linear discriminant analysis effect size was used to identify microbial components whose sequences were more abundant. Pairwise statistics provided quantitative assessment of significant distributions among groups. RESULTS: Thirty seven total samples contained high quality sequence data for subsequent analyses and divided into 3 cohorts: control (n = 10), muscle-invasive (n = 15) and superficial UC (n = 12). Control samples had significantly higher species evenness when compared to invasive (P = 0.031) and superficial tumors (P = 0.002). In addition, higher species richness was observed in noncancer versus cancer samples (Faith phylogenetic diversity, P < 0.05). Significantly enriched taxa were found in both control (Bacteroides, Lachnoclostridium, Burkholderiaceae) and cancer samples (Bacteroides and Faecalbacterium). CONCLUSION: Significantly decreased microbial community diversity was seen in the urine of patients with bladder cancer when compared to a noncancer group. Distinct taxa were noted suggesting unique microbial communities in the urine of bladder cancer patients.


Assuntos
Microbiota/fisiologia , Neoplasias da Bexiga Urinária/microbiologia , Neoplasias da Bexiga Urinária/urina , Bexiga Urinária/patologia , Idoso , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Masculino , Estudos Prospectivos
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