Pneumococcal adaptive responses to changing host environments.

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 a serotype 4 strain (TIGR4). Infection with wild-type and SpxB-negative TIGR4 resulted in decreased clearance of the SpxB-mutant, but no difference in virulence was observed for this strain, which suggests that the adaptation to the bloodstream may vary between pneumococcal serotypes or clonal complexes. Either way, the results of the study highlight SpxB as a central molecule in the adaptation of pneumococci to the various environments they may encounter in the human host. SpxB has been studied for some time as a virulence factor and except for the earliest report by Spellerberg et al [2] that indicated that the Avery strain D39 (serotype 2) lacking SpxB was attenuated for both colonization and invasive disease, which is contrary to the results in this study, reports rather consistently indicate that pneumococcal strains of various serotypes (including D39) require SpxB for optimal nasopharyngeal colonization, but that spxB is dramatically down-regulated in the lung and bloodstream [3–5]. The role of SpxB during colonization is likely multifold. SpxB activity in the presence of oxygen results in secretion of hydrogen peroxide that has been shown to protect pneumococci against other species in the nasopharyngeal microbiome [6, 7]. However, SpxB may also act to enhance colonization through improved biofilm formation in several ways. Pneumococci have recently been shown to organize as biofilms during nasopharyngeal colonization [8–10], and optimal biofilm formation requires constant bacterial Received 31 January 2014; accepted 3 February 2014; electronically published 6 February 2014. Correspondence: Anders P. Hakansson, PhD, University at Buffalo, State University of New York, 138 Farber Hall, 3435 Main St, Buffalo, NY 14214-3000 ([email protected]). The Journal of Infectious Diseases 2014;210:1–3 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/infdis/jiu084