Subversion of eukaryotic host cell pathways enables intracellular microorganisms to control cell responses, allowing avoidance of host defences and establishment of a niche in which to grow. To highlight advances in our understanding of the mechanisms by which microorganisms tailor cellular pathways to their own needs, Nature Reviews Microbiology and Nature Cell Biology present a set of specially commissioned articles that focus on some of the key pathways in host cells that are subverted by intracellular microorganisms during infection or colonization.

The topics covered range from how bacteria have adapted to replicate and grow within a host cell and avoid intracellular antimicrobial defences, to how viruses have co-opted the host cell's endocytic machinery and ubiquitin system during infection and viral replication. The mechanisms by which pathogenic bacteria subvert innate and adaptive immune responses are considered and we ask whether commensal bacteria subvert or evade these responses. This Focus Issue also features the remodelling of the host red blood cell triggered by secreted effectors of malaria parasites. The accompanying library collects the most relevant recent publications from the Nature Publishing Group.


Focus on host subversion


Nature Cell Biology 11, 509 (2009)



Life on the inside: the intracellular lifestyle of cytosolic bacteria

Katrina Ray, Benoit Marteyn, Philippe J. Sansonetti & Christoph M. Tang


Nature Reviews Microbiology 7, 333-340 (2009)

Many bacterial pathogens can invade non-phagocytic cells and survive within a membrane-bound vacuole. However, few pathogens are able to escape the vacuoles and proliferate in the host cell cytosol. In this Review, Tang and colleagues discuss the mechanisms by which these pathogens enter the cytosol, obtain nutrients and subvert host immune responses.

Virus entry by macropinocytosis

Jason Mercer & Ari Helenius


Nature Cell Biology 11, 510-520 (2009)

Viruses rely on cellular functions for their life cycle and have co-opted a number of endocytic pathways to reach a suitable cellular niche. Several viruses stimulate macropinocytosis, a mechanism for cellular fluid uptake. Mercer and Helenius review the molecular processes involved in this new mode of viral entry.

Malaria parasite proteins that remodel the host erythrocyte

Alexander G. Maier, Brian M. Cooke, Alan F. Cowman & Leann Tilley


Nature Reviews Microbiology 7, 341-354 (2009)

The malaria parasite exports an array of proteins while it resides in the erythrocytes of its host. This Review describes the functions of parasite proteins that interact with the erythrocyte membrane skeleton or that promote delivery of the major virulence protein, PfEMP1, to the erythrocyte membrane.

Viral avoidance and exploitation of the ubiquitin system

Felix Randow & Paul J. Lehner


Nature Cell Biology 11, 527-534 (2009)

The ubiquitin-proteasome pathway regulates multiple fundamental cellular processes and as such is an attractive target for subversion by pathogens. The review by Randow and Lehner discusses the various means used by viruses to subvert the ubiquitin-proteasome pathway that ultimately enable viral replication, viral exit from cells, immune evasion and viral propagation.

Antimicrobial mechanisms of phagocytes and bacterial evasion strategies

Ronald S. Flannagan, Gabriela Cosío & Sergio Grinstein


Nature Reviews Microbiology 7, 355-366 (2009)

The host cell and intracellular pathogens are in a continuous struggle. Flannagan, Cosío and Grinstein describe the pathway by which the bacteria are taken up, the antimicrobial mechanisms of the host cell and the different ways bacteria evade these mechanisms.

Targeting of immune signalling networks by bacterial pathogens

Igor E. Brodsky & Ruslan Medzhitov


Nature Cell Biology 11, 521-526 (2009)

Recent advances in our understanding of the interplay between pathogen virulence factors and host defence signalling pathways point to the emergence of common themes. Acute pathogenic infections often target signalling hubs resulting in global disruption of the host immune response, whereas persistent pathogens manipulate the host immune response by preferentially targeting signalling network nodes.



Do symbiotic bacteria subvert host immunity?

Lora V. Hooper


Nature Reviews Microbiology 7, 367-374 (2009)

The mammalian intestine is colonized by complex indigenous bacterial communities that establish beneficial symbiotic relationships with their host, making important contributions to host metabolism and digestive efficiency. In this Opinion article, Lora Hooper explores the roles of immune suppression, evasion and subversion in the establishment of these important symbiotic relationships.