Pneumococcal Adaptive Responses to Changing Host Environments

Abstract

Despite being an exclusive human pathogen, Streptococcus pneumoniae (the pneumococcus) is highly adaptable to the various host niches it encounters. It is foremost an exceptional colonizer of the human nasopharynx, where it has developed an array of strategies to adjust to both host factors and other microbial flora that reside there. Upon changes in this environment, often associated with virus infection, pneumococci may leave this environment and enter otherwise sterile sites such as the sinuses, middle ears, and lungs, from where they can disseminate further to reach the bloodstream and the meninges to cause septicemia and meningitis, respectively. The mechanisms and molecules involved in the transition and dissemination to different host environments and the adaptation required to persist in these very different host niches is not entirely clear. In a study in this issue of The Journal of Infectious Diseases [1], a group from the Karolinska Institute, led by Dr Henriques-Normark, elegantly presents us with a novel mechanism explaining how pneumococci adapt to improve their survival during invasive pneumococcal disease (IPD). The authors observed that when serotype 1 strains of 2 clonal complexes were used to infect animals, large colony variants were observed from blood cultures. Similar large colony variants could be cultured from blood of patients with IPD with pneumococcal serotype 1 strains. After sequencing the strains obtained, all large colony variants contained diverse mutations in the spxB gene, encoding pyruvate oxidase that converts pyruvate to acetyl-phosphate while using oxygen to produce hydrogen peroxide. The authors further showed that the large colony variants lacking SpxB activity were more virulent when injected intraperitoneally into mice than wild-type organisms, and that this was related to a decreased early clearance of the bacteria from the bloodstream. In contrast, the lack of SpxB made these strains less able to cause nasopharyngeal colonization. The role of SpxB deficiency was not as clear-cut when the authors used