Hypervirulent S. pneumoniae mutants discovered

Swedish researchers studying Streptococcus pneumoniae have discovered “hypervirulent” mutant forms of the bacteria that are selected for because they are more resistant to clearance by macrophages.

Birgitta Henriques-Normark (Karolinska Institutet, Stockholm, Sweden) and colleagues obtained isolates of S. pneumoniae serotype 1 from the blood of infected patients and mice. The isolates were either the CC228 strain, which is associated with low mortality, or the CC217 strain, which exhibits high mortality.

Analysis of blood samples revealed that large morphotype mutants were selected for early during the process of infection and that these mutants had either completely absent or vastly reduced hydrogen peroxide expression. Hydrogen peroxide is produced by S. pneumoniae and causes bacterial death, the researchers explain.

Interestingly, the large morphotype mutants were all found to have at least one mutation in the pyruvate oxidase gene spxB. Furthermore, the spxB mutants were shown to be hypervirulent in vivo, with mice infected with one of these mutant strains having a median survival time of 15.5 hours versus around 40 hours for wild-type strains.

Further study indicated that the hypervirulence of spxB mutants was due to decreased early clearance by macrophages; accordingly, when macrophages were depleted, spxB mutant and wild-type pneumococci showed comparable virulence in vitro.

Finally, the team showed that SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of macrophages, played an important role in clearing the spxB wild-type allele but not its mutant derivative.

Taken together, these findings suggest that spxB mutants “result in more fit, large colony variants unable to produce endogenous hydrogen peroxide”, say the researchers in the Journal of Infectious Diseases.

They note that, during the infectious process, as the bacteria move between different niches in the body, several bottlenecks will influence how mutants such as those identified here may be selected for in invasive pneumococcal disease.

“The selected mutants may differ from the parental strain in their ability to cause disease, such as what was observed for the spxB mutants, and may hence have a clinical impact even if they constitute only a fraction of the bacterial population in the blood stream,” Henriques-Normark and co-authors conclude.

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