Customizing Host Chromatin: a Bacterial Tale

Abstract

Successful bacterial colonizers and pathogens have evolved with their hosts and have acquired mechanisms to customize essential processes that benefit their lifestyle. In large part, bacterial survival hinges on shaping the transcriptional signature of the host, a process regulated at the chromatin level. Modifications of chromatin, either on histone proteins or on DNA itself, are common targets during bacterium-host cross talk and are the focus of this article.

FIGURE 1

Nuclear effectors targeting histone marks. Secreted effectors from L. monocytogenes, M. tuberculosis, and S. flexneri translocate to the nucleus, where they directly act either upon the nucleosome itself (Rv1988 and OspF), bind chromatin readers to displace them (LntA), or bind chromatin readers to dephosphorylate them (OspF). Small black arrows around modifications indicate whether they are being deposited or removed.

FIGURE 2

SET domain effectors mediate histone methylation. Effectors of C. trachomatis, M. tuberculosis, and L. pneumophila contain the eukaryotic SET domain. Once translocated to the nucleus, these effectors target histones for direct methylation either globally or at specific residues. For M. tuberculosis and L. pneumophila, this leads to repression of the host immune response and is thought to aid pathogen survival.

FIGURE 3

Targeting host DNA. Genotoxins such as CDT and colibactin induce host DNA breaks through either DNase activity (CDT) or DNA cross-linking (colibactin). M. tuberculosis targets host DNA directly for methylation with Rv2966c at non-CpG elements or induces hypomethylation through an unknown effector at CpG islands.