This repository contains scripts used to collect and analyze data from whole genome sequences of clinical Streptococcus agalactiae isolates for the following manuscript.
Intrapartum antibiotic prophylaxis selects for mutators in group B streptococci among persistently colonized patients.
The raw sequencing reads for all genomes examined in this study are available on NCBI GenBank under various BioProjects listed below:
- PRJNA1070672 (not yet publicly available), PRJNA161909, PRJNA86455, PRJNA86457, PRJNA86459, PRJNA86461, PRJNA86463, PRJNA86465, PRJNA86467, PRJNA86469, PRJNA86471, PRJNA86473, PRJNA86475, PRJNA86477, PRJNA86479, PRJNA86481, PRJNA86483, PRJNA86485, PRJNA86487, PRJNA86489, PRJNA86491, PRJNA86493, PRJNA86495, PRJNA86497, PRJNA86499, PRJNA86501, PRJNA86503, PRJNA86505, PRJNA86507, PRJNA86509, PRJNA86511, PRJNA86513, PRJNA86515, PRJNA86517, PRJNA86519, PRJNA86521, PRJNA86523, PRJNA86525, PRJNA86527, PRJNA86529, PRJNA86531, and PRJNA86533
- All BioProject, BioSample, and Genome ID information along with isolate and sequencing characteristics are listed in supplementary tables 1 and 2 associated with the manuscript
Pell, M.E.; Blankenship, H.M.; Gaddy, J.A.; Davies, H.D.; Manning, S.D. Intrapartum Antibiotic Prophylaxis Selects for Mutators in Group B Streptococci among Persistently Colonized Patients. bioRxiv 2024, 2024.04.01.587590, doi:10.1101/2024.04.01.587590.
Through vaginal colonization, GBS causes severe pregnancy outcomes including neonatal sepsis and meningitis. Although intrapartum antibiotic prophylaxis (IAP) has reduced early-onset disease rates, persistent GBS colonization has been observed in patients following prophylaxis. To determine whether IAP selects for genomic signatures that enhance GBS survival and persistence in the vaginal tract, whole-genome sequencing was performed on 97 isolates from 58 patients before (prenatal) and after (postpartum) IAP/childbirth. Core-gene mutation analysis identified 7,025 mutations between the paired isolates. Three postpartum isolates accounted for 98% of mutations and were classified as “mutators” because of point mutations within DNA repair systems. In vitro assays revealed stronger biofilms in two mutators. These findings suggest that antibiotics select for mutations that promote survival in vivo, which increases the likelihood of transmission to neonates. They also demonstrate how mutators can provide a reservoir of beneficial mutations that enhance fitness and genetic diversity in the GBS population.
We thank the Research Technology Support Facility and Michigan Department of Agriculture and Rural Development for DNA sequencing, as well as the National Center for Streptococcus (Edmonton, Alberta), particularly Marguerite Lovgren, for strain collection and serotyping. Financial support was provided by the Michigan State University (MSU) Research Foundation (to SDM) and in part, by the Michigan Sequencing and Academic Partnerships for Public Health Innovation and Response (MI-SAPPHIRE) initiative at the MDHHS via CDC through the Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases Enhancing Detection Expansion program (6NU50CK000510-02-07; to HMB and SDM). Additional support was provided by the National Institutes of Health (R01HD090061 to JAG and SDM, R01AI134036 to JAG) and Department of Veterans Affairs Merit Award I01BX005352 (Office of Research) to JAG. Student support was provided to MEP by the MSU Department of MGI via the Philipp and Vera Gerhardt Travel and Ralph Evans Awards and the MSU College of Natural Science via two Outstanding Scholar Fellowships.