A novel post-translational modification of fimbriae drives pathogenicity in Klebsiella pneumoniae

Abstract Multi-drug resistant Gram-negative bacteria, including carbapenem-resistant Klebsiella pneumoniae (CR Kp ), are a public health emergency. The predominant CR Kp sequence type worldwide is ST258. However, the factors underlying ST258’s epidemic success are not well defined. The understudied two-component system CrrAB is a genomic feature of ST258 and has been hypothesized to contribute to its global dominance. Despite this, the molecular details underpinning CrrAB’s contribution to ST258 pathogenicity are not well understood. We used RNA-sequencing to identify the regulon of CrrA and found that CrrAB induces the expression of a novel gene, encoding Crr-regulated fimbriae modifying protein (CfmP). CfmP post-translationally modifies fimbriae to significantly increase host cell adhesion and high bacterial loads within the host, consequently increasing ST258 virulence. CrrAB also drives high antibiotic resistance in CR Kp . Thus, our data places CrrAB at the intersection of virulence and antibiotic resistance supporting its function as an important regulatory system driving the pathogenicity of ST258.