Antigen 85 complex as a powerful Mycobacterium tuberculosis immunogene: Biology, immune-pathogenicity, applications in diagnosis, and vaccine design

Keikha, Masoud; Soleimanpour, Saman; Rezaee, Seyed Abdolrahim

doi:10.1016/j.micpath.2017.08.040

Cited by 107 publications

(75 citation statements)

References 74 publications

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“…Although, Ag85B is a powerful virulence factor for the bacteria, it is also an immune-dominant antigen for the host, and induces a severe response to eliminate the bacteria. As a result, high levels of ESAT-6 and CFP-10 were the best decision to replace with high levels of CFP-10, because ESAT-6 is a weaker virulence molecule than both the Ag85B and CFP-10, and even an immune-modulator for host Th1 responses 35,36 .…”

Section: Discussionmentioning

confidence: 99%

Game Theory Applications in Host-Microbe Interactions:Mycobacterium tuberculosisinfection as an example

Sharebiani

Hajimiri

Abbasnia

et al. 2019

Preprint

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The game theory describes the interactions between two players and the pay-off from wining, losing or compromising. Mycobacterium tuberculosis (Mtb)-host interactions were used as an example for the application of the game theory to describe and predict the possibilities of victory for any players. The gene expression for eight main markers of host response and three Mtb virulence factors were assessed in broncho-alveolar lavage of TB + and TB  patients. The game theory showed that a variety of paths exist that players can use, in response to the behaviour of the counterpart. Briefly, according to the "Nash equilibrium", Ag85B is the main virulence factor for Mtb in active phase, however it is the most immunogenic factor if the host can respond by high expression of T-bet and iNOS. In this situation, Mtb can express high levels of ESAT-6 and CFP10 and change the game to the latency, in which host responses by medium expression of T-bet and iNOS and medium level of TGF-β and IDO. Consistently, The IDO expression was 134-times higher in TB + s than the TB  s, and the T-bet expression, ~200-times higher in the TB  s than the TB + s. Furthermore, Mtb-Ag85B had a strong positive association with CCR2, T-bet and iNOS, but had a negative correlation with IDO. Introduction 19When two organisms, individuals, parties, teams, or even countries interact, the outcome 20 varies greatly, depending on the intention of each party involved 1 . Attempts to quantify these 21 interactions can be assessed, using game theory models. Game theory is a mathematical 22 framework, describing the outcome (pay-off) resulted from specific interactions (game) 23 between two individuals (players) 2,3 . In biologic context, game theory can describe 24 interactions between a host and its parasite through epigenetic strategies, and the resulting 25 pay-off from healthy, infected, or disease onset. The conflict is very complex, as both 26 organisms are responsible for resisting and helping the associated genus to survive. In other 27 words, host-microbe interactions are complex assemblies of large numbers of phenomena that 28 are interacting competitively under multifactorial environmental conditions 1-3 . 29Bacteria and its host under stress may carry out the sophisticated principles of game theory, in 30 order to decide whether to compromise or invade for elimination of the danger 4 . Rationality 31 of game theory indicates that each player in a particular game is motivated by maximizing his 32 own pay-off. Therefore, it is especially important for players to think about each other's 33 strategic choice and react accordingly 4 . Interactions between Mycobacterium tuberculosis 34 (Mtb) and human (players) are often included in the Mtb's strategies to invade host responses, 35 to replicate and persist within the host, and on the other hand, the host attempts to induce 36 appropriate responses to eliminate the infection 5 . Particularly, in case of Mtb infection these 37 interactions are in a strict completion, as the microbe has adapted to replic...

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Section: Discussionmentioning

confidence: 99%

Game Theory Applications in Host-Microbe Interactions:Mycobacterium tuberculosisinfection as an example

Sharebiani

Hajimiri

Abbasnia

et al. 2019

Preprint

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“…LpqH, the 19 kDa glycolipoprotein, participates in MO infection as an adhesin that binds the mannose receptor triggering the phagocytosis of bacilli and downregulating MHC-II antigen presentation interfering with TLR2 and MAPK signaling [23]. The APA antigen plays a prominent role in Mtb virulence; it functions as a mycoyl-transferase that catalyzes the attachment of mycolic acids to arabinogalactan and the biogenesis of cord factor, a very active virulence factor [25]. APA is expressed at the bacterial surface, which explains its interaction with fibronectin, elastin and the surfactant protein A. LprG, the 25-kDa glycolipoprotein transports ManLAM to the mycobacterial cell-wall and as an adhesin it may bind the MO mannose receptor facilitating phagocytosis and inhibition of the phagosome-lysosome fusion.…”

Section: Phagosome Acidification In Macrophages That Have Engulfed Phmentioning

confidence: 99%

Phosphate starvation enhances phagocytosis of Mycobacterium bovis/BCG by macrophages.

Espinosa-Cueto

Magallanes-Puebla

Mancilla

2020

Preprint

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Tuberculosis (TB) is an important health problem worldwide. The only available TB vaccine is Mycobacterium bovis bacillus Calmette-Guerin, a saprophytic mycobacterium that activates the innate and the acquired immune system after being phagocytosed by macrophages and dendritic cells. BCG vaccination fails to prevent adult pulmonary TB although it may have a protective effect in childhood TB. Understanding how BCG interacts with macrophages and other immunocompetent cells is crucial to develop new vaccines. In this study we showed that macrophages phagocytose Mycobacterium bovis /BCG bacilli with higher efficiency when they are cultured without phosphate. The increased phagocytosis is associated with diminished phagosome acidification. We isolated mycobacterial cell wall and membranes to search for mycobacterial molecules that could be involved in these processes; by immunoblot, it was found that the plasma membranes of phosphate-deprived bacilli express the adhesins PstS-1, LpqH, LprG, and the APA antigen. These proteins are not detected in membranes of bacilli grown with usual amounts of phosphate. The interest of our observations is to show that under the metabolic stress implied in phosphate deprivation, mycobacteria respond upregulating adhesins that could improve their capacity to infect macrophages. These observations are relevant to understand how M. bovis/ BCG induces protective immunity.

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“…In Mycobacterium tuberculosis, the antigen 85 complex (Ag85) consists of three paralogous proteins (Ag85A-C) that are secreted at high levels and elicit strong humoral as well as cell-mediated immune 2 of 14 responses [11][12][13]. Although they are secreted into the extracellular milieu in large amounts, there is strong evidence that a proportion remains cell surface associated [7,[14][15][16][17][18][19] where they participate via their mycolyltransferase activity in synthesis of the mycomembrane [20] ( Figure 1A).…”

Section: Introductionmentioning

confidence: 99%

Mechanical Forces between Mycobacterial Antigen 85 Complex and Fibronectin

Viljoen

Alsteens

Dufrêne

2020

Cells

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Adhesion to extracellular matrix proteins is an important first step in host invasion, employed by many bacterial pathogens. In mycobacteria, the secreted Ag85 complex proteins, involved in the synthesis of the cell envelope, are known to bind to fibronectin (Fn) through molecular forces that are currently unknown. In this study, single-molecule force spectroscopy is used to study the strength, kinetics and thermodynamics of the Ag85-Fn interaction, focusing on the multidrug-resistant Mycobacterium abscessus species. Single Ag85 proteins bind Fn with a strength of~75 pN under moderate tensile loading, which compares well with the forces reported for other Fn-binding proteins. The binding specificity is demonstrated by using free Ag85 and Fn peptides with active binding sequences. The Ag85-Fn rupture force increases with mechanical stress (i.e., loading rate) according to the Friddle-Noy-de Yoreo theory. From this model, we extract thermodynamic parameters that are in good agreement with previous affinity determinations by surface plasmon resonance. Strong bonds (up to~500 pN) are observed under high tensile loading, which may favor strong mycobacterial attachment in the lung where cells are exposed to high shear stress or during hematogenous spread which leads to a disseminated infection. Our results provide new insight into the pleiotropic functions of an important mycobacterial virulence factor that acts as a stress-sensitive adhesin.

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Antigen 85 complex as a powerful Mycobacterium tuberculosis immunogene: Biology, immune-pathogenicity, applications in diagnosis, and vaccine design

Cited by 107 publications

References 74 publications

Game Theory Applications in Host-Microbe Interactions:Mycobacterium tuberculosisinfection as an example

Game Theory Applications in Host-Microbe Interactions:Mycobacterium tuberculosisinfection as an example

Phosphate starvation enhances phagocytosis of Mycobacterium bovis/BCG by macrophages.

Mechanical Forces between Mycobacterial Antigen 85 Complex and Fibronectin

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