Remains of infection

Abstract

commentaries The Journal of Clinical Investigation http://www.jci.org Volume 122 Number 7 July 2012 2345 sible posttreatment spirochetes in their mouse model. But more important were the experiments using real-time imaging of transgenic fluorescent B. burgdorferi in mice and the transplantation of cartilagi- nous tissue to naive mice to assess anti- genicity and mitogenicity (2). The results of these latter experiments provide com- pelling evidence that there are residues of the bacteria in the form of protein if not transcribable DNA continuing to cause mischief long after bacterial life has ceased. The authors, with justification, propose that this accounts for the phenomenon of antibiotic-refractory Lyme arthritis as well perhaps as less distinctive musculoskeletal manifestations after treatment. One conceptualization of the different possible states between a viable, proliferat- ing bacterium and its total absence as well as the predicted outcomes of the different detection measures is shown in Figure 1. This depicts a spirochete and a cell-wall– active antibiotic, but would apply to other types of bacteria and, in modified form, to antibiotics that have other targets. The spi- rochete shown missing a cell wall may rep- licate in this state and revert to the usual morphology corresponding to descrip- tions of L-forms. Beyond this state, there may possibly be replication, but neither reversion nor the possibility of transmis- sion. Finally there are membrane blebs, which may or may not contain nucleic acids, and then only proteins. Either of the last two states could be what Bockenstedt et al. observed (2). A wider angle view Drawing back from the close-up shot on this Lyme disease controversy, can we see connections in the background with other infectious diseases and their posttreatment outcomes? Would these in-depth studies of persistence of pathogen viability and resid- ual DNA and proteins in a host have arisen in the absence of a medical and social con- tro