Cracking the antigenic code of mycobacteria: CFP-10/ESAT-6 tuberculosis skin test and misleading results

There are different tuberculosis diagnostic tools available that detect an antigen-specific immune response. The present study aims to evaluate the potential of cross-reactive responses of a CFP-10 and ESAT-6 antigen-based TB test using bioinformatics tools. The study found that the presence of the sequences coding for the CFP-10 and ESAT-6 antigens in mycobacterial genomes is not associated with their pathogenicity, and not even consistent within a single species among its strains, which can lead to either false positive or false negative test results. The data that was analyzed included genome assemblies of all available mycobacterial strains obtained from the NCBI Genome database, while the standalone BLAST and tblastn programs were utilized to detect the presence of the CFP-10 and ESAT-6 sequences. The findings revealed that a number of non-pathogenic mycobacteria contained the aforementioned sequences, while some pathogenic mycobacteria did not, indicating that a standard tuberculin skin test should be more preferable for detecting various pathogenic mycobacteria compared to antigen-specific tests. In the Mycobacterium tuberculosis complex (MTBC), the proportion of positive strains varied within individual species, indicating a complex relationship. Among non-tuberculous mycobacteria (NTMB), more than half of the analyzed species did not contain these sequences which is consistent with their non-pathogenicity. Further research is necessary to fully comprehend the relationship between MTBC pathogenicity and the CFP-10 and ESAT-6 sequences. This could lead to a conclusion that a standard tuberculin skin test, although non-specific due to the undefined antigen content, may be able to detect various pathogenic mycobacteria in a more reliable manner than antigen-specific tests.