CRISPR Interference Can Prevent Natural Transformation and Virulence Acquisition during In Vivo Bacterial Infection

• Published in: Cell host & microbe Vol. 12; no. 2; pp. 177 - 186
• Main Authors: Bikard, David, Hatoum-Aslan, Asma, Mucida, Daniel, Marraffini, Luciano A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16-08-2012; Elsevier
• Subjects: Animals; Bacterial Proteins; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Base Sequence; Gene Transfer, Horizontal; Genetics; Humans; Inverted Repeat Sequences; Life Sciences; Mice; Microbiology and Parasitology; Molecular Sequence Data; Pneumococcal Infections; Pneumococcal Infections - microbiology; Streptococcus pneumoniae; Streptococcus pneumoniae - genetics; Streptococcus pneumoniae - pathogenicity; Streptococcus pneumoniae - physiology; Transformation, Genetic; Virulence
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2012.06.003

Pathogenic bacterial strains emerge largely due to transfer of virulence and antimicrobial resistance genes between bacteria, a process known as horizontal gene transfer (HGT). Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci of bacteria and archaea encode a sequence-specific defense mechanism against bacteriophages and constitute a programmable barrier to HGT. However, the impact of CRISPRs on the emergence of virulence is unknown. We programmed the human pathogen Streptococcus pneumoniae with CRISPR sequences that target capsule genes, an essential pneumococcal virulence factor, and show that CRISPR interference can prevent transformation of nonencapsulated, avirulent pneumococci into capsulated, virulent strains during infection in mice. Further, at low frequencies bacteria can lose CRISPR function, acquire capsule genes, and mount a successful infection. These results demonstrate that CRISPR interference can prevent the emergence of virulence in vivo and that strong selective pressure for virulence or antibiotic resistance can lead to CRISPR loss in bacterial pathogens.
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► CRISPR immunity prevents natural transformation in vitro and in vivo ► Strong selection for the transfer of virulent traits leads to loss of CRISPR activity ► CRISPR/Cas loci constitute a barrier to the evolvability of bacterial pathogens ► Engineered CRISPR/Cas loci could be used as a sequence-specific therapeutic