mGem: A quarter century with the Pirofski-Casadevall damage response framework-a dynamic construct for understanding microbial pathogenesis

Abstract

A quarter of a century ago, Liise-anne Pirofski and Arturo Casadevall shared their concepts of microbial pathogenesis through the lens of a damage-response framework (DRF), which characterizes disease by assessing the dynamic interactions between the host and pathogen as reflected by damage as the readout. This framework has evolved to be a powerful tool for understanding the biology of complex infectious diseases, analyzing emerging and reemerging microbes, and developing therapeutic approaches to combat infections. The DRF is also frequently used to explain research at scientific meetings and to teach microbial pathogenesis to diverse learners. This mGem reviews how the DRF came to be and provides an overview of how it is used. Without a doubt, the scientific community will continue to leverage the DRF to advance research and innovate therapeutic approaches, which is especially important as new and reemerging infectious diseases threaten global health.

Keywords: education; microbial pathogenesis; scientific framework.

Fig 1

The original six classes of damage–response curves comprising the Pirofski–Casadevall DRF (9). The amount of host damage is shown on the Y axis with the strength of the associated host response presented on the X axis. A variable is present in classes 2, 3, and 5 to represent a range in damage given differences in individual hosts. Reproduced from reference with permission.

Fig 2

Exemplars of how therapeutic interventions can markedly shift damage–response curves in the Pirofski–Casadevall DRF (9). Reproduced from reference with permission.