Mycobacterium tuberculosis Binds Human Serum Amyloid A, and the Interaction Modulates the Colonization of Human Macrophages and the Transcriptional Response of the Pathogen

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,...

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Published in:Cells (Basel, Switzerland) Switzerland), 2021-05, Vol.10 (5), p.1264
Main Authors: Kawka, Malwina, Brzostek, Anna, Dzitko, Katarzyna, Kryczka, Jakub, Bednarek, Radosław, Płocińska, Renata, Płociński, Przemysław, Strapagiel, Dominik, Gatkowska, Justyna, Dziadek, Jarosław, Dziadek, Bożena
Format: Article
Language:English
Subjects:
Acute phase proteins
Antigens
Bacilli
Colonization
Drug resistance
Homeostasis
host-pathogen interaction
human macrophages
Infections
Lipoproteins
Macrophages
Membrane proteins
Mycobacterium tuberculosis
Operons
Opsonization
Pathogens
Pattern recognition
Phagocytes
Proteins
serum amyloid A
Surfactants
Transcription
Tuberculosis
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Summary: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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10051264