Influence of salt and temperature in the growth of pathogenic free-living amoebae

Among the many genera of free-living amoebae that exist in nature, members of only four genera have an association with human disease: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri and Sappinia diploidea. Acanthamoeba spp. and B. mandrillaris are opportunistic pathogens causing infections of the central nervous system, lungs, sinuses and skin, mostly in immunocompromised humans. Balamuthia is also associated with disease in immunocompetent children, and Acanthamoeba spp. cause a sight-threatening infection, Acanthamoeba keratitis, mostly in contact-lens wearers. Of more than 30 species of Naegleria, only one species, N. fowleri, causes an acute and fulminating meningoencephalitis in immunocompetent children and young adults. In addition to human infections, Acanthamoeba, Balamuthia and Naegleria can cause central nervous system infections in animals. Because only one human case of encephalitis caused by Sappinia diploidea is known, generalizations about the organism as an agent of disease are premature. In this review we summarize what is known of these free-living amoebae, focusing on their biology, ecology, types of disease and diagnostic methods. We also discuss the clinical profiles, mechanisms of pathogenesis, pathophysiology, immunology, antimicrobial sensitivity and molecular characteristics of these amoebae.

Naegleria fowleri has generated tremendous media attention over the last 5 years due to several high-profile cases. Several of these cases were followed very closely by the general public. N. fowleri is a eukaryotic, free-living amoeba belonging to the phylum Percolozoa. Naegleria amoebae are ubiquitous in the environment, being found in soil and bodies of freshwater, and feed on bacteria found in those locations. While N. fowleri infection appears to be quite rare compared to other diseases, the clinical manifestations of primary amoebic meningoencephalitis are devastating and nearly always fatal. Due to the rarity of N. fowleri infections in humans, there are no clinical trials to date that assess the efficacy of one treatment regimen over another. Most of the information regarding medication efficacy is based on either case reports or in vitro studies. This review will discuss the pathogenesis, diagnosis, pharmacotherapy, and prevention of N. fowleri infections in humans, including a brief review of all survivor cases in North America.

Free-living amoebas (FLA) are ubiquitous environmental protists that have enormously contributed to the microbiological contamination of water sources. FLAs have displayed resistance to environmental adversities and germicides and have played important roles in the population control of microbial communities due to its predatory behavior and microbicidal activity. However, some organisms have developed resistance to the intracellular milieu of amoebas, as in the case of Acanthamoebas, which in turn, have been functioning as excellent reservoirs for amoeba-resistant microorganisms (ARMs), such as bacteria, viruses and fungi. Little is known about these relationships and interaction mechanisms, but it is speculated that the FLAs need a very broad repertoire or universal class of receptors to bind and recognize these diverse species of microorganisms. By harboring these organisms as a "Trojan Horse", the Achantamoeba has been working as an excellent vector for pathogens. Moreover, studies have demonstrated that the interaction of pathogens with Acanthamoeba results in environmental selective pressure responsible for induction and maintenance of virulence factors and increase in microbial pathogenicity. This phenomenon is correlated to the observation of higher gene number and DNA content of ARMs, when compared to their relatives which are adapted to other hosts, due to allopatric or sympatric gene transfer and acquisition, contradicting the overall genome reduction theory for intracellularly adapted pathogens. Thus, adaptation to FLAs indirectly provided a "learning" environment for pathogens to resist later to macrophages; besides the evolutionary distance, these phagocytes share similar predatory mechanisms, such as phagocytosis and phagolysossomal degradation. In this mini-review, we cover the most important aspects of Acanthamoeba biology and their interactions with endemically important human pathogens.