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Published on: February 28, 2025
Mycobacterium tuberculosis Pili promote adhesion to and invasion of THP-1 macrophages
Saiyur Ramsugit1, Manormoney Pillay
1Medical Microbiology and Infection Control, University of KwaZulu-Natal.
Abstract:
Central to the paradigm of the pathogenesis of Mycobacterium tuberculosis is its ability to attach to, enter, and subsequently survive in host macrophages. However, little is known regarding the bacterial adhesins and invasins involved in this interaction with host macrophages. Pili are cell-surface structures produced by certain bacteria and have been implicated in adhesion to and invasion of phagocytes in several species. M. tuberculosis pili (MTP) are encoded by the Rv3312A (mtp) gene. In the present study, we assessed the ability of a Δmtp mutant and an mtp-complemented clinical strain to adhere to and invade THP-1 macrophages in comparison with the parental strain by determining colony-forming units. Both adhesion to and invasion of macrophages, although not reaching significance, were markedly reduced by 42.16% (P = 0.107) and 69.02% (P = 0.052), respectively, in the pili-deficient Δmtp mutant as compared with the wild-type. The pili-overexpressing complemented strain showed significantly higher levels of THP-1 macrophage adhesion (P = 0.000) and invasion (P = 0.040) than the mutant. We, thus, identified a novel adhesin and invasin of M. tuberculosis involved in adhesion to and invasion of macrophages.
Insights
Mycobacterium tuberculosis pili (MTP) act as novel adhesins and invasins, facilitating bacterial entry and survival within host macrophages. This study highlights MTP
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Mycobacterium tuberculosis pathogenesis involves macrophage interaction.
- Bacterial adhesins and invasins mediating this interaction are poorly understood.
- Pili are bacterial surface structures implicated in adhesion and invasion.
Purpose of the Study:
- To investigate the role of Mycobacterium tuberculosis pili (MTP) in macrophage adhesion and invasion.
- To identify MTP as a novel adhesin and invasin.
Main Methods:
- Generated a Δmtp mutant and an mtp-complemented strain of M. tuberculosis.
- Assessed bacterial adhesion to and invasion of THP-1 macrophages using colony-forming unit assays.
- Compared the wild-type, mutant, and complemented strains.
Main Results:
- The Δmtp mutant showed reduced adhesion (42.16%) and invasion (69.02%) of macrophages compared to the wild-type.
- The pili-overexpressing complemented strain exhibited significantly higher adhesion (P = 0.000) and invasion (P = 0.040) than the mutant.
- These findings suggest MTP's role in M. tuberculosis-macrophage interactions.
Conclusions:
- Mycobacterium tuberculosis pili (MTP) function as novel adhesins and invasins.
- MTP are crucial for M. tuberculosis adhesion to and invasion of host macrophages.
- Targeting MTP could offer new therapeutic strategies against tuberculosis.
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