RNA-Seq unveils new attributes of the heterogeneous Salmonella-host cell communication.

High-throughput RNA sequencing (RNA-Seq) has uncovered hundreds of small RNAs and complex modes of RNA regulation in every bacterium analyzed to date. This complexity agrees with the adaptability of most bacteria to varied environments including, in the case of pathogens, the new niches encountered in the host. Recent RNA-Seq studies have analyzed simultaneously gene expression in the intracellular pathogen Salmonella enterica and infected host cells at population and single-cell level. Distinct polarization states or interferon responses in the infected macrophage were linked to variable growth rates or activities of defined virulence regulators in intra-phagosomal bacteria. Intracellular Salmonella, however, exhibit disparate intracellular lifestyles depending the host cell, ranging from a hyper-replicative cytosolic state in epithelial cells to a non-replicative intra-phagosomal condition in varied host cell types. The basis of such diverse pathogen-host communications could be examined by RNA-Seq studies in single intracellular Salmonella cells, certainly a challenge for future investigations.