CRISPR-Cas: to take up DNA or not-that is the question

Abstract

Landmark experiments in the 1920s showed that capsule switching is critical for Streptococcus pneumonia survival. Further studies demonstrated that capsule "transformation" occurs via DNA uptake. In this issue of Cell Host and Microbe, Bikard et al. (2012) show that CRISPR-Cas systems inhibit DNA uptake, selecting for the outgrowth of CRISPR-defective pneumococci.

Figure 1

Top row: The seminal 1928 experiments of Griffith (1928), who found that injection of a rough (un-encapsulated) strain of S. pneumoniae rarely killed mice (top left), whereas injection of a smooth (encapsulated) strain did, and the smooth strain could be recovered from the dead mouse. Injection of heat-killed encapsulated bacteria (grey smooth) did not kill mice, but the combination of live rough S. pneumoniae together with heat-killed encapsulated S. pneumoniae established a productive infection that killed the mice. Moreover, when the bacteria recovered from the dead mice were cultured, they had ‘transformed’ from rough to smooth (Griffith, 1928). In the present work (Bikard et al., 2012), Birkard and colleagues showed that if the rough strain carried a functional CRISPR-Cas system that was designed to target a capsule gene, the transformation to smooth, virulent S. pneumoniae was blocked. Further, these investigators showed that when they forced the experiment using larger doses of bacteria, one mouse died and smooth bacteria were in fact recovered. These bacteria had mutated their CRISPR-Cas system, rendering it non-functional and unable to block the uptake of capsular DNA.