Despite the great strides medicine has made in the past century, diagnosing infectious disease remains a difficult – and often impossible – task. One major barrier in diagnosis is the simple problem of knowing what to look for. Which of the millions of potentially antigenic products that a pathogen makes can actually be found in bodily fluids and used as indicators of infection? After all, not every protein or polysaccharide belonging to a pathogen can make it into a handy sample of urine or blood, so which CAN we use?
A study in mBio this week brings us a little closer to identifying those antigens that could be used in diagnostics. Using a technique they call In vivo Microbial Antigen Discovery (InMAD), Nuti et al. were able to amplify the small signals present in an infected mouse’s blood by purifying serum samples and using them to immunize another mouse. Serum from this second mouse contains antibodies for the bacterial components in the blood of the first mouse. They used this serum to probe blots of bacterial lysates and bacterial proteome arrays. The spots on the blot or the array that lit up indicate which antigens the mouse immune system reacts to – precisely the antigens that could be targeted in an assay.
For the model bacteria they used, Burkholderia pseudomallei and Francisella tularensis, Nuti et al. identified proteins, capsular polysaccharide and lipopolysaccharides that could be used to develop quick assays for infection. A key benefit of their approach, they say, is that it makes no assumptions about the structure, synthesis or secretion of target antigens, so the technique has the potential to be a useful means for discovering diagnostic targets from pathogens.