Bacterial adaptation contributes to pneumococcal threat in sickle cell disease patients

Researchers have identified differences in the genetic code of pneumococcal bacteria that may explain why it poses such a risk to children with sickle cell disease and why current vaccines don’t provide better protection against the infection. St. Jude Children’s Research Hospital scientists led the study, which appeared earlier this month in the journal Cell Host & Microbe.

The analysis showed the bacteria have adapted to sickle cell patients, including measures aimed at preventing infection. As a result, disease-causing strains of the bacteria differ in children with and without sickle cell disease. “The results help explain why current vaccines haven’t been as successful at protecting children with sickle cell disease from pneumococcal infections as they have in protecting other children,” says Joshua Wolf, MD, one of the study’s lead authors.

Scientists compared the genomes of 322 pneumococcal bacteria collected from sickle cell patients between 1994 and 2011 to DNA from 327 strains obtained from individuals without sickle cell disease. The analysis revealed that over time, the genomes of bacteria isolated from sickle cell patients shrank as genes and the corresponding DNA were discarded or combined. A comparison of the bacterial genomes from individuals with and without sickle cell disease suggested the changes reflected bacterial adaptation to their sickle cell host and contributed to the bacteria’s ability to persist despite advances in preventive care.

Using a technique called transposon sequencing (Tn-seq), researchers showed that the bacteria’s ability to cause widespread infection in mice with and without sickle cell disease was dramatically affected by changes in 60 different bacterial genes. The results demonstrated that bacteria faced different conditions in animals with and without sickle cell disease.

When researchers checked those same genes in bacteria isolated from sickle cell patients, they found six that were missing or altered in a significant percentage of samples. The list included genes involved in transporting iron into bacteria, bacterial metabolism, and other processes that are likely altered in patients with sickle cell disease. Read the study abstract.