Despite immense achievements in the past century in hygiene control, and the development of vaccines and antibiotics, infectious diseases continue to pose a tremendous threat to public health globally. There are still devastating infections for which there are no effective vaccines or antimicrobial therapies. Moreover, the problem of drug resistance in bacteria and viral populations and the increasing appreciation that pathologies resulting from infections are responsible for a number of chronic conditions, are creating an ever-growing need for novel preventive and therapeutic approaches. In line with this, a new host-targeted approach has been suggested for antimicrobial drug research that exploits the central role of the host cell during infection. Decades of research have taught us that infections are supported by host cell functions, and that infection pathology is frequently host dependent. Accordingly, the pharmacological targeting of host cell factors promises novel opportunities to prevent and treat infectious disease. Such an approach may be anticipated to expand the number of druggable targets, produce broad-spectrum compounds and impede the generation of resistance. The discovery of RNA interference (RNAi) has created opportunities to explore gene functions in cellular systems in a targeted manner. RNAi loss-of-function approaches have proved invaluable for the identification of host proteins important for pathogen viability. These approaches can be applied on a high-throughput scale, which demands sophisticated liquid handling and high-content image analysis. Here, we provide an overview of the current status of high-content screening (HCS) in loss-of-function analyses in infectious disease research and discuss how these powerful techniques can be applied to identify host factors with previously unknown roles in infection and its pathology.

The challenge of fighting infectious diseases

Infections by pathogenic species of bacteria, viruses, fungi and protozoa have had considerable impact on mankind throughout history. Advances in our understanding of the importance of hygiene control, and later, improvements in diagnostics and the development and successful employment of vaccines and antimicrobial drugs, have substantially benefited human health, and provided social and economic benefits.