1. Introduction
The genus
Fusarium is considered one of the most adaptable and versatile in Eumycota. One of its most economically important species is
FOX, an invasive phytopathogen responsible for vascular wilt and cortical rot in more than a hundred crops of commercial interest.
FOX is responsible for a large percentage of economic losses in the agricultural sector worldwide. These phytopathogens have host specialization capacity and high virulence, becoming a broad complex of
FOX species with a high probability of new pathogens
[1]. This complexity of species has gained considerable attention in the scientific community in recent years. The Molecular Plant Pathology Journal has included
FOX among the “Top 10” of the phytopathogenic fungi based on its scientific and economic importance
[2].
FOX complexes are distributed worldwide. The pathogen accumulates in sufficient inoculums, and then a susceptible cultivar is planted. The symptoms of the plant can be evidenced through chlorotic flakes, which undergo curvature and lose structural stability. The plant eventually wilts which can be evidenced by acquiring a yellowish-brown color while the vascular system changes color from light yellow to brick red. Most of the forms in
FOX complexes exist as chlamydospores, which remain latent in the host’s tissue and soil until they stimulate germination, with exudates from the roots responsible for their germination. Various pathogenic forms of
FOX can enter the host root through wounds or directly through the root tips
[3][4].
The impact of the
FOX species complex has generated millions of economic losses. In banana crops
[5][6][7], the losses caused by the TR4 race of
F. oxysporum f. sp. were estimated at USD 2000 million during the “Gros Michel” era. TR4 is currently expected to cause even more significant losses eventually: in Latin America, from 1995, the disease of Panama was reported in most banana producing regions, except Papua New Guinea, the South Pacific Islands, and some of the countries bordering the Mediterranean; in Indonesia, Taiwan, Malaysia, China, and the Philippines, losses of around USD 253 million were estimated between 2011 and 2013
[8][9]. In tomato, the only vegetable crop cultivated globally, vital for the daily diet and consumed as freshly unprocessed fruits, millions of losses have been reported due to vascular wilt caused by
FOX [10]. A reduction in 50% of Africa production has been reported for oil palm due to vascular wilt caused by
FOX [3][11].
Moreover, huge losses have been reported in melon crops caused by
FOX, carnation, and chrysanthemum flowers and cotton
[12]. In countries such as the USA, China, and India, which provide approximately 35% of the total fiber use globally,
FOX f. sp.
vasinfectum diseases caused losses between 0.4 and 1.0%
[13]. In Colombia, the cape gooseberry (
Physalis peruviana L.) production suffered significantly from 2009–2013 due to the
FOX complexes’ proliferation
[14].
In addition to the enormous impact caused in agriculture and the economy, it is known that the toxins secreted by
FOX complexes can cause alteration in animals and humans health
[15]. The disease caused by eating food with mycotoxins is called mycotoxicosis. Several hundred compounds have been described as toxic or potentially toxic secondary metabolites of
FOX complexes with high toxicity, demonstrated in bioassays or feeding studies. Some mycotoxins, such as enniatins, fusaric acids—inducers of cell death in tomato plants—and moniliformin, have been linked to toxicosis in humans or livestock animals immunocompromised infections in humans
[16][17]. A risk factor for fusariosis can occur in immunocompetent patients due to tissue degradation caused by trauma, severe burns, or foreign bodies in the body. Infections in humans with
FOX complexes can cause local, focally invasive, or disseminated diseases. Skin lesions can be seen in approximately 75% of cases and are usually located on the trunk and extremities, causing keratitis and onychomycosis.
Fusarium can also affect deep skin ulcers, third-degree burns, and surgical wounds. In other cases, the infection remains localized in the immunocompetent or immunosuppressed host, causing manifestations such as septic arthritis, skin infection, central line sepsis, endophthalmitis, osteomyelitis, cystitis, and brain abscess
[18][19][20][21].
To perform effective control of
FOX complexes is one of the most difficult to achieve. Therefore, various methods have been developed, such as cultural, biological, botanical, genetic, and chemical controls. Some fungi have been evaluated more frequently in biological control methodologies than bacteria, such as
Trichoderma (53% of fungi)
[22][23]. Non-pathogenic
Fusarium species (23%) and
Penicillium (10%) are other used microorganisms. Concerning the bacteria uses,
Pseudomonas (44%), followed by
Bacillus (13%) and
Streptomyces (9%), has been broadly employed
[24]. Despite the advantages of biological control, microorganisms and botanicals can show a low range of efficiency levels. Nearly a third of the tested microorganisms have been shown to reduce the disease by only 10% to 40%. As for botanicals, most of the reported studies were performed only in vitro tests. These considerations lead to the question of the level of efficiency required to consider the marketing of a biological control product and restrict their field of application
[12].
Genetic investigations on
FOX complexes have shown promissory results towards phytopathogen control. Recent comparative analysis of the
FOX genomes provided information on the genome’s organization and the genomic region that governs pathogenicity, revealing that each specialist form’s effector repertoire probably determines the specificity of the host
[25]. Through comparative analysis, pathogenicity-related chromosomes have been identified in
FOX that contain genes for host-specific virulence
[26]. On the other hand, genetic engineering advances have been possible using new resistant genotypes of several plants through gene editing and high-performance phenotyping. These success factors depend on the genotype and are related to the level of resistance to
FOX complexes. Strategies for integrated management should consider increasing plant defenses and suppressing
FOX complexes in the soil once the disease is present
[9][27][28]. However, the productivity and market acceptance for somaclones is lower, and there is low and expensive productivity, especially in small markets for other cultivars. Due to these considerations, pests’ chemical control through chemical products (agrochemicals as pesticides) is the most profitable and effective alternative for crops in large areas.
Fungicides with a benzimidazole group in their structure, such as benomyl, carbendazim, and thiabendazole, have demonstrated their capacity to control
FOX complexes in vitro and under greenhouse conditions. Other agrochemicals such as cyproconazole, propiconazole, and prochloraz showed reduced
Fusarium wilt disease of about 80% in banana plants. Soil fumigated with methyl bromide effectively reduced Panama disease in South Africa for a few months. However, the fungus was able to repopulate these soils and infect susceptible banana plants. Phosphonate compounds are potent against this phytopathogen as they reduce fungal growth under in vitro conditions. Carbendazim injections into the corm tissue of Rasthali cultivars in India provided short-term tolerance, but the results were erratic with the same treatments in other parts of the world. The disinfection processes of contaminated machinery and agricultural implements used sodium hypochlorite and detergents effectively against conidia and chlamydospores of
F. oxysporum f. sp. However, they do not apply to large plantations, and it is known that they cause some environmental risks and even harm farmers
[9][29][30]. In some countries, prochloraz and azoxystrobin replaced benomyl to control various ornamental
Fusarium wilts and bulb cultures. However, prochloraz has never been registered for ornamental plants in the USA. The price of azoxystrobin has limited its use in many bulb crops
[5].
Despite this, several measures must be considered when using agrochemicals since the side effects can be even more harmful than the pathogen. These effects only appear when the amount of pesticide in the body is more significant than what it can eliminate, so it accumulates and reaches the toxic level
[31]. Frequent use of pesticides can harden or stunt cultivars of a species. Combined with the incomplete effectiveness of chemical treatments against
Fusarium wilt, these considerations have made chemical control disappointing for farmers and the productive sector. Many times, “cocktails” of the mentioned agrochemicals are used, enhancing their effects and causing chemical alterations that originate new chemical substances
[32]. The use of these mixtures and their storage without due control has caused severe health disorders for producers and their families, mainly at the reproduction level. The increased risks during pesticide application often result from a lack of information, knowledge, awareness, and inadequate supervision during the application and sale of highly toxic products. Due to this, several alternatives have been sought that allow chemical pest control to be carried out with minimal impact. Specifically, to reduce fungi’s presence in the post-harvest stage, studies have been carried out that contemplate the use of extracts from resistant plants
[33]. This alternative is impressive considering that the secondary metabolites with biological activity are the terpenoid type, phenolic compounds, phenylpropanoids, stilbenes, alkaloids, saponins, and heterocyclic compounds
[34], whose advantage corresponds to their rapid degradation in the soil. Therefore, new agrochemical agents’ synthesis continues to be a profitable one and still to be explored. In this review, we present a compendium of organic compounds active against different species of
FOX, their synthesis methods, and some recommendations and perspectives of the authors, formulated during the process of consolidation of the information to redirect the search for new molecules active against
FOX systematically and rationally.