Beefing up the manipulation of the immune system: a novel prophage in Indian Staphylococcus aureus

In a paper, just published in PLoS ONE, we report the presence of a novel prophage (viral DNA that is integrated in the host bacterial chromosome) in the genome of S. aureus from India (sequence type 772). This prophage carries two toxins, both of which are capable of manipulating the host immune system.

In collaboration with Dr. Gayathri Arakere from the Indian Institute of Science, we had previously obtained draft genome sequences of several Indian clinical isolates of the disease-causing Staphylococcus aureus. The bioinformatics was carried out by Supriya in the lab and the bulk of the experiments by Sushma Prabhakara from Dr. Arakere's lab. The sequencing was performed by Ramya and Chandana in the genomics facility, led by Dr. Malali Gowda, at C-CAMP, Bangalore.

The abstract reads as follows:

Staphylococcus aureus is a major human pathogen, first recognized as a leading cause of hospital-acquired infections. Community-associated S. aureus (CA-SA) pose a greater threat due to increase in severity of infection and disease among children and healthy adults. CA-SA strains in India are genetically diverse, among which is the sequence type (ST) 772, which has now spread to Australia, Europe and Japan. Towards understanding the genetic characteristics of ST772, we obtained draft genome sequences of five relevant clinical isolates and studied the properties of their PVL-carrying prophages, whose presence is a defining hallmark of CA-SA. We show that this is a novel prophage, which carries the structural genes of the hlb-carrying prophage and includes the sea enterotoxin. This architecture probably emerged early within the ST772 lineage, at least in India. The sea gene, unique to ST772 PVL, despite having promoter sequence characteristics typical of low expression, appears to be highly expressed during early phase of growth in laboratory conditions. We speculate that this might be a consequence of its novel sequence context. The crippled nature of the hlb-converting prophage in ST772 suggests that widespread mobility of the sea enterotoxin might be a selective force behind its ‘transfer’ to the PVL prophage. Wild type ST772 strains induced strong proliferative responses as well as high cytotoxic activity against neutrophils, likely mediated by superantigen SEA and the PVL toxin respectively. Both proliferation and cytotoxicity were markedly reduced in a cured ST772 strain indicating the impact of the phage on virulence. The presence of SEA alongside the genes for the immune system-modulating PVL toxin may contribute to the success and virulence of ST772.

We are funded by NCBS (DAE), DST, CSIR, DBT. and UGC