Antibiotic resistance has recently been pointed out as one of the major risks for human health. Streptococcus pyogenes (group A streptococcus; GAS) is among the top ten causes of mortality within infectious disease causing a variety of acute infections, among which necrotizing fasciitis (NSTI) presents as a rapidly progressing invasive infection. Biofilm in the tissue of patients - with decreased sensitivity to standard antibiotic treatment - is a complicating microbiological feature in NSTI. There is an urgent need to reconsider antibiotic standard treatment protocols for NSTI as well as the development of new tools to quickly identify tailored therapies for individual patients.
We have applied isothermal microcalorimetry to investigate host-pathogen interactions by monitoring growth, biofilm formation and antibiotic treatment efficacy in a tissue- or tissue-like context of GAS strains from NSTI patients. This method allows for real-time measurement of metabolic activity early after bacterial introduction into the tissue like-milieu. Organotypic skin tissue or fibroblast cell layers infected with GAS NSTI strains revealed apparent differences in growth behavior in the tissue milieu when compared to routinely used bacterial medium. In addition, striking differences in antibiotic efficacy for single antibiotics or combinations thereof in tissue settings versus liquid medium could be visualized.
We present isothermal microcalorimetry as a semi-high throughput assay to investigate bacterial behavior in a tissue-like setting. This method can mimic in vivo biofilm and treatment thereof, making it suitable to screen antibiotics suggested for clinical use. In addition, we present data supporting this method for a broader use also for other important pathogens, such as for example Staphylococcus aureus.