Characterization of a novel yeast phase-specific antigen expressed during in vitro thermal phase transition of Talaromyces marneffei

Abstract

Talaromyces marneffei is a dimorphic fungus that has emerged as an opportunistic pathogen particularly in individuals with HIV/AIDS. Since its dimorphism has been associated with its virulence, the transition from mold to yeast-like cells might be important for fungal pathogenesis, including its survival inside of phagocytic host cells. We investigated the expression of yeast antigen of T.marneffei using a yeast-specific monoclonal antibody (MAb) 4D1 during phase transition. We found that MAb 4D1 recognizes and binds to antigenic epitopes on the surface of yeast cells. Antibody to antigenic determinant binding was associated with time of exposure, mold to yeast conversion, and mammalian temperature. We also demonstrated that MAb 4D1 binds to and recognizes conidia to yeast cells’ transition inside of a human monocyte-like THP-1 cells line. Our studies are important because we demonstrated that MAb 4D1 can be used as a tool to study T.marneffei virulence, furthering the understanding of the therapeutic potential of passive immunity in this fungal pathogenesis.

In Vitro Susceptibility of Talaromyces Marneffei In Malaysia: Comparison of Yeast and Mycelial Phases

“…T. marneffei has become one of the most common opportunistic pathogens in Southeast Asia, southern China and northeastern India [21]. It is a primary cause of morbidity and mortality in HIV-infected and other immunosuppressed patients who live in endemic areas including Malaysia [22].…”

Talaromyces marneffei Infection: Virulence, Intracellular Lifestyle and Host Defense Mechanisms

“…From antigenic expression studies, dimorphism inside in vitro host macrophages at 37 • C is different from that achieved in artificial culture medium alone [20]. T. marneffei infected macrophages contain the unicellular yeast cells which proliferate within these innate immune cells.…”

“…In macrophage, they rapidly undergo morphogenic transition to the yeast form and multiply intracellularly. In vitro studies with the murine macrophage cell line (J774A.1) and THP-1 human macrophage cell lines demonstrate that conidia replicate intracellularly by binary fission and express yeast phase specific antigen within 24 h of phagocytosis [20,32] (Figure 1). Subsequently, rather than being eliminated by the natural killing mechanism of the macrophage, T. marneffei are able to subvert the natural killing mechanisms of macrophages to survive and replicate inside the After establishing infection inside alveolar phagocytes, T. marneffei (predominantly in the parasitic yeast cell form) can readily spread in a Trojan horse manner within these host cells throughout the host resulting in systemic infection [14,34].…”

“…In healthy individuals, engulfed conidia are, for example, killed by host macrophages through the production of oxidative burst as well as the action of lysosomal enzymes. However, as with other pathogenic fungi such as Histoplasma, T. marneffei can survive and replicate inside the phagosomal compartment of macrophages [18][19][20][21]. Hence, T. marneffei is classified as a facultative intracellular pathogen as it is found inside macrophages and tissue histiocytes in talaromycosis patients [14,22].…”

Fungicidal Activity of Recombinant Javanicin against Cryptococcus neoformans Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes

“…Mass spectra (MS) and MS/MS spectra were obtained in positive-ion mode at 2 Hz over the range (m/z) 150-2200. The collision energy was adjusted to 10 eV as a function of the m/z value [50]. The LC-MS analysis of each sample was done in triplicate.…”