lactoferrin and Mucormycosis

Mucormycosis is a deadly infection which is caused by fungi of the order Mucorales including species belonging to the genus Rhizopus, Mucor, Mycocladus, Rhizomucor, Cunninghamella, and Apophysomyces. Despite antifungal therapy and surgical procedures, the mortality rate of this disease is about 90-100% which is exceptionally high. The hypersensitivity of patients with raised available serum iron indicates that the Mucorales are able to use host iron as a critical factor of virulence. This is because iron happens to be a crucial element playing its role in the growth of cells and development. In this review, we have described Lactoferrin (Lf) as a potential iron-chelator. Lf is a naturally occurring glycoprotein which is expressed in most of the biological fluids. Moreover, Lf possesses exclusive anti-inflammatory effects along with several anti-fungal effects that could prove to be helpful to the pathological physiology of inexorable mucormycosis cases. This literature summarises the biological insights into the Lf being considered as a potential fungistatic agent and an immune regulator. The review also proposes that unique potential of Lf as an iron-chelator can be exploited as the adjunct treatment for mucormycosis infection.

Topics: Animals; Antifungal Agents; Host-Pathogen Interactions; Humans; Iron; Iron Chelating Agents; Lactoferrin; Mucorales; Mucormycosis; Predictive Value of Tests; Risk Factors

Evidence suggests that neutrophils are important in host defenses against invasive aspergillosis and mucormycosis, although hyphae in these lesions are too large to be phagocytized. Interactions of neutrophils with hyphae of Aspergillus fumigatus and Rhizopus oryzae were studed in vitro. Light and electron microscopic observations indicated that neutrophils attached to and spread over the surfaces of hyphae, even in the absence of serum. This was followed by dramatic morphologic changes which suggested severe damage and probably death of hyphae. An assay of neutrophil-induced reduction of uptake of radioisotopes was used to quantitate damage to the fungi by neutrophils from normal subjects. Damage to hyphae was inhibited by a variety of compounds which are known to affect neutrophil surface functions, motility, and metabolism. Use of inhibitors of oxidative microbicidal mechanisms of neutrophils indicated the central importance of these mechanisms in damage to hyphae. Inhibitors of neutrophil cationic proteins altered damage only to Rhizopus. Damage to hyphae by lysozyme suggested that it may play a secondary role in the neutrophil, primarily against Aspergillus. This new nonphagocytic mechanism may play an important role in host defenses against these and other hyphal forms of fungi.

Topics: Aspergillosis; Aspergillus fumigatus; Humans; Lactoferrin; Mucormycosis; Muramidase; Neutrophils; Rhizopus