Host range, morphological and genomic characterisation of bacteriophages with activity against clinical Streptococcus agalactiae isolates

PLoS One. 2020 Jun 23;15(6):e0235002. doi: 10.1371/journal.pone.0235002. eCollection 2020.

Abstract

Streptococcus agalactiae or Group B Streptococcus (GBS) is a leading cause of sepsis in neonates. As a preventative measure prophylactic antibiotic administration is common in pregnant women colonised with GBS, but antibiotic-resistance and adverse effects on neonatal microbiomes may result. Use of bacteriophages (phages) is one option for targeted therapy. To this end, four phages (LF1 -LF4) were isolated from wastewater. They displayed lytic activity in vitro against S. agalactiae isolates collected from pregnant women and neonates, with 190/246 isolates (77.2%) and 10/10 (100%) isolates susceptible to at least one phage, respectively. Phage genomes ranged from 32,205-44,768 bp and all phages were members of the Siphoviridae family. High nucleotide identity (99.9%) was observed between LF1 and LF4, which were closely related to a putative prophage of S. agalactiae. The genome organisation of LF2 differed, and it showed similarity to a different S. agalactiae prophage, while LF3 was more closely related to a Streptococcus pyogenes phage. Lysogenic gene presence (integrase, repressor and regulatory modules), was suggestive of temperate phages. In a therapeutic context, temperate phages are not ideal candidates, however, the broad host range activity of these phages observed on clinical isolates in vitro is promising for future therapeutic approaches including bioengineered phage or lysin applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Viral / isolation & purification
  • Female
  • Genomics
  • Host Specificity / genetics
  • Humans
  • Infant, Newborn
  • Lysogeny
  • Neonatal Sepsis / microbiology
  • Neonatal Sepsis / therapy*
  • Phage Therapy*
  • Phylogeny
  • Pregnancy
  • Siphoviridae / genetics*
  • Siphoviridae / isolation & purification
  • Streptococcus Phages / genetics*
  • Streptococcus Phages / isolation & purification
  • Streptococcus agalactiae / isolation & purification
  • Streptococcus agalactiae / virology*
  • Streptococcus pyogenes / virology

Substances

  • DNA, Viral

Grants and funding

This research was supported by the Channel 7 Telethon Trust Fund to MSP. LLF is supported by the Australian Government Research Training Program Scholarship and the Professor Gordon King Postgraduate Scholarship provided by the Women’s and Infants’ Research Foundation. MSP is also supported by an NHMRC Project Grant [1144040].