A genomic approach to understand interactions between Streptococcus pneumoniae and its bacteriophages

Bacteriophage replication depends on bacterial proteins and inactivation of genes coding for such host factors should interfere with phage infection. To gain further insights into the interactions between S. pneumoniae and its pneumophages, we characterized S. pneumoniae mutants selected for resistance to the virulent phages SOCP or Dp-1.

S. pneumoniae R6-SOCP(R) and R6-DP1(R) were highly resistant to the phage used for their selection and no cross-resistance between the two phages was detected. Adsorption of SOCP to R6-SOCP(R) was partly reduced whereas no difference in Dp-1 adsorption was noted on R6-DP1(R). The replication of SOCP was completely inhibited in R6-SOCP(R) while Dp-1 was severely impaired in R6-DP1(R). Genome sequencing identified 8 and 2 genes mutated in R6-SOCP(R) and R6-DP1(R), respectively. Resistance reconstruction in phage-sensitive S. pneumoniae confirmed that mutations in a GntR-type regulator, in a glycerophosphoryl phosphodiesterase and in a Mur ligase were responsible for resistance to SOCP. The three mutations were additive to increase resistance to SOCP. In contrast, resistance to Dp-1 in R6-DP1(R) resulted from mutations in a unique gene coding for a type IV restriction endonuclease.

The characterization of mutations conferring resistance to pneumophages highlighted that diverse host genes are involved in the replication of phages from different families.