Stress Responses and Mechanisms of Phytopathogens Infecting Humans: Threats, Drivers, and Recommendations

Cross-kingdom infections, where pathogens from one kingdom infect organisms of another, were historically regarded as rare anomalies with minimal concern. However, emerging evidence reveals their increasing prevalence and potential to disrupt the delicate balance between plant, animal, and human health systems. Traditionally recognized as plant-specific, a subset of phytopathogens, including certain fungi, bacteria, viruses, and nematodes, have demonstrated the capacity to infect non-plant hosts, particularly immunocompromised individuals. These pathogens exploit conserved molecular mechanisms, such as immune evasion strategies, stress responses, and effector proteins, to breach host-specific barriers and establish infections. Specifically, fungal pathogens like Fusarium spp. and Colletotrichum spp. employ toxin-mediated cytotoxicity and cell-wall-degrading enzymes, while bacterial pathogens, such as Pseudomonas syringae, utilize type III secretion systems to manipulate host immune responses. Viral and nematode phytopathogens also exhibit molecular mimicry and host-derived RNA silencing suppressors to facilitate infections beyond plant hosts. This review features emerging cases of phytopathogen-driven animal and human infections and dissects the key molecular and ecological determinants that facilitate such cross-kingdom transmission. It also highlights critical drivers, including pathogen plasticity, horizontal gene transfer, and the convergence of environmental and anthropogenic stressors that breach traditional host boundaries. Furthermore, this review focuses on the underlying molecular mechanisms that enable host adaptation and the evolutionary pressures shaping these transitions. To address the complex threats posed by cross-kingdom phytopathogens, a comprehensive One Health approach that bridges plant, animal, and human health strategies is advocated. Integrating molecular surveillance, pathogen genomics, AI-powered predictive modeling, and global biosecurity initiatives is essential to detect, monitor, and mitigate cross-kingdom infections. This interdisciplinary approach not only enhances our preparedness for emerging zoonoses and phytopathogen spillovers but also strengthens ecological resilience and public health security in an era of increasing biological convergence.