Purpose of review Microsporidia have emerged as causes of opportunistic infections associated with diarrhea and wasting in AIDS patients. This review describes recent reports of microsporidiosis in HIV-infected individuals and the growing awareness of microsporidiosis in non-HIV-infected populations. Recent findings Microsporidia were only rarely recognized as causes of disease in humans until the AIDS pandemic. Implementation of combination antiretroviral therapy (cART) to curtail HIV replication and restore immune status drastically reduced the occurrence of opportunistic infections, including those due to microsporidia, in HIV-infected individuals. In developing countries where cART is not always accessible, microsporidiosis continues to be problematic. Improvement of diagnostic methods over the previous 25 years led to identification of several new species of microsporidia, many of which disseminate from enteric to systemic sites of infection and contribute to some unexpected lesions. Among non-HIV-infected but immune-suppressed individuals, microsporidia have infected organ transplant recipients, children, the elderly, and patients with malignant disease and diabetes. In otherwise healthy immune-competent HIV seronegative populations, self-limiting diarrhea occurred in travelers and as a result of a foodborne outbreak associated with contaminated cucumbers. Keratitis due to microsporidiosis has become problematic and a recent longitudinal evaluation demonstrated that non-HIV-infected individuals seropositive for microsporidia who had no clinical signs continued to intermittently shed organisms in feces and urine. Summary Greater awareness and implementation of better diagnostic methods are demonstrating that microsporidia contribute to a wide range of clinical syndromes in HIV-infected and non-HIV-infected people. As such, microsporidia should be considered in differential diagnoses if no other cause can be defined.

Microsporidia are obligate intracellular pathogens related to Fungi. These organisms have a unique invasion organelle, the polar tube, which upon appropriate environmental stimulation rapidly discharges out of the spore, pierces a host cell’s membrane, and serves as a conduit for sporoplasm passage into the host cell. Phylogenetic analysis suggests that microsporidia are related to the Fungi, being either a basal branch or sister group. Despite the description of microsporidia over 150 years ago, we still lack an understanding of the mechanism of invasion, including the role of various polar tube proteins, spore wall proteins, and host cell proteins in the formation and function of the invasion synapse. Recent advances in ultrastructural techniques are helping to better define the formation and functioning of the invasion synapse. Over the past 2 decades, proteomic approaches have helped define polar tube proteins and spore wall proteins as well as the importance of posttranslational modifications such as glycosylation in the functioning of these proteins, but the absence of genetic techniques for the manipulation of microsporidia has hampered research on the function of these various proteins. The study of the mechanism of invasion should provide fundamental insights into the biology of these ubiquitous intracellular pathogens that can be integrated into studies aimed at treating or controlling microsporidiosis.

Microsporidia are obligate intracellular pathogens identified ∼150 years ago as the cause of pébrine, an economically important infection in silkworms. There are about 220 genera and 1,700 species of microsporidia, which are classified based on their ultrastructural features, developmental cycle, host-parasite relationship, and molecular analysis.

Toxoplasma gondii infects up to one third of the world's population. A key to the success of T. gondii as a parasite is its ability to persist for the life of its host as bradyzoites within tissue cysts. The glycosylated cyst wall is the key structural feature that facilitates persistence and oral transmission of this parasite. Because most of the antibodies and reagents that recognize the cyst wall recognize carbohydrates, identification of the components of the cyst wall has been technically challenging. We have identified CST1 (TGME49_064660) as a 250 kDa SRS (SAG1 related sequence) domain protein with a large mucin-like domain. CST1 is responsible for the Dolichos biflorus Agglutinin (DBA) lectin binding characteristic of T. gondii cysts. Deletion of CST1 results in reduced cyst number and a fragile brain cyst phenotype characterized by a thinning and disruption of the underlying region of the cyst wall. These defects are reversed by complementation of CST1. Additional complementation experiments demonstrate that the CST1-mucin domain is necessary for the formation of a normal cyst wall structure, the ability of the cyst to resist mechanical stress, and binding of DBA to the cyst wall. RNA-seq transcriptome analysis demonstrated dysregulation of bradyzoite genes within the various cst1 mutants. These results indicate that CST1 functions as a key structural component that confers essential sturdiness to the T. gondii tissue cyst critical for persistence of bradyzoite forms. Toxoplasma gondii causes severe encephalitis in immune compromised hosts after reactivation of brain cysts that persist for the life span of the host. The biological mechanisms of bradyzoite persistence within cysts are not fully understood. The glycosylated cyst wall is thought to play a crucial role in survival of bradyzoites during chronic infection as well as successful oral transmission of infection. Here we have identified the gene encoding cyst wall glycoprotein CST1. When we delete the CST1 gene, parasites form dramatically fragile brain cysts. Parasites lacking CST1 develop fewer brain cysts, show dysregulation of bradyzoite-specific gene expression and are less able to grow under stressed conditions. The rescue of these phenotypes requires the heavily glycosylated mucin domain of CST1. These studies demonstrate that the glycosylation of CST1 plays a significant role in the structural integrity and persistence of brain cysts. Agents that perturb CST1 glycosylation have the potential to disrupt formation of latent brain cysts, preventing chronic Toxoplasma infection.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboranes, and BODIPY, for the treatment of different human diseases.In addition, we also describe the synthesis, key structure–activity relationship, and associated biological activities, such as antimicrobial, antituberculosis, antitumor, antiparasitic, antiprotozoal, anti-inflammatory, antifolate, antidepressant, antiallergic, anesthetic, and anti-Alzheimer’s agents, as well as proteasome and lipogenic inhibitors. This compilation could be very useful in the exploration of novel boron-derived compounds against different diseases, with promising efficacy and lesser side effects.

Microsporidia are found worldwide and both vertebrates and invertebrates can serve as hosts for these organisms. While microsporidiosis in humans can occur in both immune competent and immune compromised hosts, it has most often been seen in the immune suppressed population, e.g. patients with advanced HIV infection, patients who have had organ transplantation, those undergoing chemotherapy, or patients using other immune suppressive agents. Infection can be associated with either focal infection in a specific organ (e.g. keratoconjunctivitis, cerebritis, or hepatitis) or with disseminated disease. The most common presentation of microsporidiosis being gastrointestinal infection with chronic diarrhea and wasting syndrome. In the setting of advanced HIV infection or other cases of profound immune deficiency microsporidiosis can be extremely debilitating and carries a significant mortality risk. Microsporidia are transmitted as spores which invade host cells by a specialized invasion apparatus the polar tube. This review summarizes recent studies that have provided information on the composition of the spore wall and polar tube, as well as insights into the mechanism of invasion and interaction of the polar tube and spore wall with host cells during infection.