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Background  The bacterium  Burkholderia mallei  is the etiological agent of glanders, a highly contagious, often fatal zoonotic infectious disease that is also a biodefense concern. Clinical laboratory assays that analyze blood or other biological fluids are the highest priority because these specimens can be collected with minimal risk to the patient. However, progress in developing sensitive assays for monitoring  B. mallei  infection is hampered by a shortage of useful biomarkers.    Results  Reasoning that there should be a strong correlation between the proteomes of infected tissues and circulating serum, we employed imaging mass spectrometry (IMS) of thin-sectioned tissues from  Chlorocebus aethiops  (African green) monkeys infected with  B. mallei  to localize host and pathogen proteins that were associated with abscesses. Using laser-capture microdissection of specific regions identified by IMS and histology within the tissue sections, a more extensive proteomic analysis was performed by a technique that combined the physical separation capabilities of liquid chromatography (LC) with the sensitive mass analysis capabilities of mass spectrometry (LC-MS/MS). By examining standard formalin-fixed, paraffin-embedded tissue sections, this strategy resulted in the identification of several proteins that were associated with lung and skin abscesses, including the host protein calprotectin and the pathogen protein GroEL. Elevated levels of calprotectin detected by ELISA and antibody responses to GroEL, measured by a microarray of the bacterial proteome, were subsequently detected in the sera of  C. aethiops, Macaca mulatta,  and  Macaca fascicularis  primates infected with  B. mallei .    Conclusions  Our results demonstrate that a combination of multidimensional MS analysis of traditional histology specimens with high-content protein microarrays can be used to discover lead pairs of host-pathogen biomarkers of infection that are identifiable in biological fluids.    Electronic supplementary material  The online version of this article (doi:10.1186/s12014-015-9079-4) contains supplementary material, which is available to authorized users.

Serum biomarkers of Burkholderia mallei infection elucidated by proteomic imaging of skin and lung abscesses