**4. Discussion**

There have been several species identified to date that infect both plants and animals. These species range from the extreme, such as *Agrobacterium tumefaciens*, which infects fungi, plants, and animals [27], to the more common species that co-infect plants and animals, including *Aspergillus fumigatus*, *Pleurostomophora richardsiae*, *Pseudomonas aeruginosa*, *Pythium insidiosum*, *Rhizopus oryzae*, *Sporothrix schenckii*, *Staphylococcus aureus*, and *Trichoderma longibrachiatum* [28]. Studies on the infection mechanism in plant hosts, particularly at the immune system level, have revealed that certain features are shared within animal hosts [29]. It is commonly accepted that in plant–animal co-infections, the pathogen is dependent on its ability to recruit iron from the host or environment [30]. Previous studies on *Fusarium* have tried to establish the cross-kingdom pathogenicity between plants, mammals, and insects [31–33]; however, to our knowledge, the present study is the first report to demonstrate this infective property between plants and humans.

*Fusarium* is one cause of disease in a wide variety of crops as maize, although it does not produce the same lethality in animals as it does in plants [34]. This might be due to differences between the two kingdoms during pattern recognition by the receptors of innate immune cells [35], which could allow *Fusarium* to evade the host's immune defenses. One important difference is that the main components of a blood circulatory system, i.e., macrophages, neutrophils, and dendritic cells are not found in plants. In this sense, the pathogenic outcome in both kingdoms can range from lethal to non-lethal outcomes. This may also cause a different clinical result, resulting in a distinct disease with completely different consequences. Taking this into account, there may be two different diseases produced by the same microbial pathogen, which intriguingly appears to contradict to Koch's third postulate [36]. Just as the well-known evidence of exemptions to Koch's postulates, it shows that not all parasites can be isolated in artificial media, single isolated pathogens could also produce different symptoms depending on the nature of the host and tissue. A very clear example of this is the fact that *Salmonella* spp. can live within plants without producing any lethal effects, while in animals it is fatal. Although *Fusarium* rarely causes a disease harmful enough to lead to mortality in healthy humans, it can be lethal for plant species. It will be interesting in the future to investigate the similarities between how pathogens escape in order to establish disease. The present research may also facilitate our understanding of how some host species survive an infection while others perish from the same pathogen.

In summary, we investigated whether *Fusarium* species isolated from keratomycosis human patients, which are normally pathogens of plants, conserve their infective capacity to re-infect plants and other human tissue. We demonstrated that *Fusarium* spp. conserves their infective mechanism for colonizing human tissue and plants and for back-infecting other human tissue, such as nails. Our results also found a new exemption to Koch's third postulate, as the same fungal pathogen was seen to produce two different diseases. This work could serve as a reference for demonstrating cyclic *Fusarium* reinfections between plants and humans. It thus suggests that the infective mechanism of *Fusarium* could be conserved. Further, Omics studies will help to elucidate how *Fusarium* changes its infective mechanism (gene expression and physiology) to adapt to hosts from a different kingdom.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2076-2607/8/6/947/s1, Figure S1. Summary of patient characteristics infected by *Fusarium keratitis*. (A) The Mexican states involved in this study, with percentages of keratitis for each. (B) Distribution of *Fusarium* keratitis by gender. (C) Distribution of patient occupations. (D) Distribution of patient age groups.

**Author Contributions:** Conceptualization, F.R.Q.-F.; investigation, T.M.-M., J.Q.-C., L.M.G.-P., N.R.-M., V.V.-Z., L.S., M.S.-L., G.G.-C. and R.K.S.; formal analysis, T.M.-M. and F.R.Q.-F.; writing and data curation, T.M.-M., R.K.S., L.S. and F.R.Q.-F.; validation, F.R.Q.-F. All authors have read and agreed to the published version of the manuscript.

**Funding:** The authors are grateful to the Mexican National Council on Science and Technology (CONACyT) for financial support from Infraestructura no. 250738, Frontera de la Ciencia no. 1070 and SIP 20195805.

**Acknowledgments:** We wish to thank H. Cámara de Diputados for the Insignia Project "Proyecto de equipamiento en medio ambiente". We are grateful to Brandon Loveall of IMPROVENCE for proofreading the manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.
