<i>Mycobacterium tuberculosis</i> Binds Human Serum Amyloid A, and the Interaction Modulates the Colonization of Human Macrophages and the Transcriptional Response of the Pathogen
Malwina Kawka,
Anna Brzostek,
Katarzyna Dzitko,
Jakub Kryczka,
Radosław Bednarek,
Renata Płocińska,
Przemysław Płociński,
Dominik Strapagiel,
Justyna Gatkowska,
Jarosław Dziadek,
Bożena Dziadek
Affiliations
Malwina Kawka
Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland
Anna Brzostek
Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland
Katarzyna Dzitko
Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland
Jakub Kryczka
Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland
Radosław Bednarek
Department of Cytobiology and Proteomics, Medical University of Lodz, 92-215 Lodz, Poland
Renata Płocińska
Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland
Przemysław Płociński
Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland
Dominik Strapagiel
Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland
Justyna Gatkowska
Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland
Jarosław Dziadek
Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland
Bożena Dziadek
Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland
As a very successful pathogen with outstanding adaptive properties, Mycobacterium tuberculosis (Mtb) has developed a plethora of sophisticated mechanisms to subvert host defenses and effectively enter and replicate in the harmful environment inside professional phagocytes, namely, macrophages. Here, we demonstrated the binding interaction of Mtb with a major human acute phase protein, namely, serum amyloid A (SAA1), and identified AtpA (Rv1308), ABC (Rv2477c), EspB (Rv3881c), TB 18.6 (Rv2140c), and ThiC (Rv0423c) membrane proteins as mycobacterial effectors responsible for the pathogen-host protein interplay. SAA1-opsonization of Mtb prior to the infection of human macrophages favored bacterial entry into target phagocytes accompanied by a substantial increase in the load of intracellularly multiplying and surviving bacteria. Furthermore, binding of human SAA1 by Mtb resulted in the up- or downregulation of the transcriptional response of tubercle bacilli. The most substantial changes were related to the increased expression level of the genes of two operons encoding mycobacterial transporter systems, namely, mmpL5/mmpS5 (rv0676c), and rv1217c, rv1218c. Therefore, we postulate that during infection, Mtb-SAA1 binding promotes the infection of host macrophages by tubercle bacilli and modulates the functional response of the pathogen.