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Papain-like cysteine proteases (PLCPs) play pivotal roles in plant defense against pathogen invasions. While pathogens can secrete effectors to target and inhibit PLCP activities, the roles of PLCPs in plant-virus interactions and the mechanisms through which viruses neutralize PLCP activities remain largely uncharted. Here, we demonstrate that the expression and activity of a maize PLCP CCP1 (Corn Cysteine Protease), is upregulated following sugarcane mosaic virus (SCMV) infection. Transient silencing of CCP1 led to a reduction in PLCP activities, thereby promoting SCMV infection in maize. Furthermore, the knockdown of CCP1 resulted in diminished salicylic acid (SA) levels and suppressed expression of SA-responsive pathogenesis-related genes. This suggests that CCP1 plays a role in modulating the SA signaling pathway. Interestingly, NIa-Pro, the primary protease of SCMV, was found to interact with CCP1, subsequently inhibiting its protease activity. A specific motif within NIa-Pro termed the inhibitor motif was identified as essential for its interaction with CCP1 and the suppression of its activity. We have also discovered that the key amino acids responsible for the interaction between NIa-Pro and CCP1 are crucial for the virulence of SCMV. In conclusion, our findings offer compelling evidence that SCMV undermines maize defense mechanisms through the interaction of NIa-Pro with CCP1. Together, these findings shed a new light on the mechanism(s) controlling the arms races between virus and plant. Author summary: PLCPs perform crucial roles in plant defense against invasions by pathogens. While pathogens can secrete effectors that target and inhibit PLCP activities, the functions of PLCPs in plant-virus interactions and the mechanisms by which viruses counteract PLCP activities remain largely unexplored. In this study, we demonstrate that a maize PLCP termed CCP1 confers resistance to SCMV infection via SA signaling pathway. Conversely, SCMV NIa-Pro interacts with CCP1 and inhibits its protease activity to allow efficient viral infection. Furthermore, we have discovered that the critical amino acids responsible for the interaction between NIa-Pro and CCP1 are crucial for the virulence of SCMV. [ABSTRACT FROM AUTHOR]

Candida albicans, the primary etiology of human mycoses, is well-adapted to catabolize proline to obtain energy to initiate morphological switching (yeast to hyphal) and for growth. We report that put1-/- and put2-/- strains, carrying defective Proline UTilization genes, display remarkable proline sensitivity with put2-/- mutants being hypersensitive due to the accumulation of the toxic intermediate pyrroline-5-carboxylate (P5C), which inhibits mitochondrial respiration. The put1-/- and put2-/- mutations attenuate virulence in Drosophila and murine candidemia models and decrease survival in human neutrophils and whole blood. Using intravital 2-photon microscopy and label-free non-linear imaging, we visualized the initial stages of C. albicans cells infecting a kidney in real-time, directly deep in the tissue of a living mouse, and observed morphological switching of wildtype but not of put2-/- cells. Multiple members of the Candida species complex, including C. auris, are capable of using proline as a sole energy source. Our results indicate that a tailored proline metabolic network tuned to the mammalian host environment is a key feature of opportunistic fungal pathogens. Author summary: Candida albicans is listed as one of four "critical priority" fungal pathogens by the World Health Organization (WHO). Intriguingly, C. albicans is a natural commensal organism thriving in symbiosis with other components of the human microflora. Given the opportunistic character of C. albicans, it is important to understand how nutrient availability within host microenvironments contribute to the transition from commensal to pathogenic growth. Here, we report that proline is catabolized by C. albicans as an important energy source, a characteristic that is conserved among other pathogenic Candida species, including the multidrug resistant C. glabrata and C. auris. Using different infection models and applying a state-of-the-art intravital imaging technique to visualize C. albicans cells infecting kidneys in a living mouse, we observed that strains unable to utilize proline exhibit significantly reduced virulence and filamentous hyphal growth. Genetic dissection of the Proline UTilization (PUT) pathway and deciphering the control mechanisms governing proline use led to the discovery that proline is toxic to cells unable to catabolize this amino acid. Our findings provide novel insights implicating proline metabolism as a key determinant of pathogenic fungal growth. [ABSTRACT FROM AUTHOR]