Group B Streptococcus bacteriophages with broad clinical host range (#239)
As a leading cause of sepsis in neonates, Streptococcus agalactiae or Group B Streptococcus (GBS) is a significant obstetric pathogen. Numerous screening strategies have been implemented world-wide to identify mothers at risk of transmitting the organism to their newborn. Risk-based strategies and detection of GBS by culture screening all result in antibiotic administration. Although penicillin remains effective, resistance is inevitable and the impact of antibiotic administration on the maternal and neonatal microbiomes is not well-understood. An ideal treatment option would be one in which GBS are targeted in colonized women, with no effect on commensal organisms. Use of bacteriophage (phage) therapy, is one such option. Four phages (LF1 – LF4) were isolated from wastewater using standard enrichment techniques. All phages showed varied and broad ranging activity against clinical GBS isolates collected from pregnant women (colonising) and neonates (disease). Phages displayed lytic activity in vitro against antenatal GBS isolates with 73.3% of GBS isolates (n = 135) susceptible to at least one phage. LF2 and LF4 showed activity against all neonatal disease-causing isolates (n=10), while LF1 was also active against 90% of these isolates. Transmission electron microscopy confirmed all phages as members of the Siphoviridae family. Whole genome sequencing revealed genomes ranging from 32,205 – 44,768 bp. LF1 and LF4 share 99.9% nucleotide identity and are closely related to putative prophage of GBS. LF2 shows homology to a different putative prophage, although its genome organisation differs, while LF3 exhibits genome similarity to a Streptococcus pyogenes phage. The presence of genes required for lysogeny including integrase, repressor and regulatory modules suggests all are temperate phages, which are not typically used for phage therapy, however, the in vitro activity of these phages against a broad range of clinically important isolates is extremely promising and they may have therapeutic use as bioengineered phages or purified lysins.