When attempting to propagate infections, bacterial pathogens encounter phagocytes that encase them in vacuoles called phagosomes. Within phagosomes, bacteria are bombarded with a plethora of stresses that often lead to their demise. However, pathogens have evolved numerous strategies to counter those host defenses and facilitate survival. Given the importance of phagosome–bacteria interactions to infection outcomes, they represent a collection of targets that are of interest for next-generation antibacterials. To facilitate such therapies, different approaches can be employed to increase understanding of phagosome–bacteria interactions, and these can be classified broadly as top down (starting from intact systems and breaking down the importance of different parts) or bottom up (developing a knowledge base on simplified systems and progressively increasing complexity). Here we review knowledge of phagosomal compositions and bacterial survival tactics useful for bottom-up approaches, which are particularly relevant for the application of reaction engineering to quantify and predict the time evolution of biochemical species in these death-dealing vacuoles. Further, we highlight how understanding in this area can be built up through the combination of immunology, microbiology, and engineering.

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