High-Resolution Three-Dimensional Whole-Organ Tomography of Microbial Infections

Bacteria infections are a major threat to human health. Antimicrobial resistance is increasing, and vaccines are still lacking for several major pathogens. To identify novel avenues for control strategies, we need to know more about how pathogens respond to the host immune system, and to antibiotics in vivo in the infected tissues.

Surviving bacteria can cause relapses if antimicrobials fail to eradicate an infection. Using serial tomography, we show that typhoid fever causing salmonella can persist during therapy in a specific part of the spleen. Inflammation is weak in this region, which disrupts the critical synergy between antibiotics and inflammation for effective clearance.

Bacteria are micrometer-sized objects. It is difficult to localize such small objects in their tissue context. Serial two-photon tomography can detect one single bacterium in centimeter-sized organs, and determine its replication rate.

We can also detect immune cells, such as neutrophils, and determine their spatial relationship with the bacteria. We study the activities of bacteriostatic antibiotics. These antibiotics can cure infections, although they can only inhibit bacterial growth without actually killing the pathogen.

We also determine the spreading of bacterial mutants that lack certain virulence factors, and the impact of immune defects on infection and treatment.