Evasion of phagotrophic predation by protist hosts and innate immunity of metazoan hosts byLegionella pneumophila

Abstract

Summary Legionella pneumophila is a ubiquitous environmental bacterium that has evolved to infect and proliferate within amoebae and other protists. It is thought that accidental inhalation of contaminated water particles by humans is what has enabled this pathogen to proliferate within alveolar macrophages and cause pneumonia. However, the highly evolved macrophages are equipped more sophisticated innate defense mechanisms than protists, such as the evolution of phagotrophic feeding into phagocytosis with more evolved innate defense processes. Not surprisingly, the majority of proteins involved in phagosome biogenesis (~80%) have origins in the phagotrophy stage of evolution. There are a plethora of highly evolved cellular and innate metazoan processes, not represented in Protist biology, that are modulated by L. pneumophila; including TLR2 signaling, NF-κB, apoptotic and inflammatory processes, histone modification, caspases, and the NLRC-Naip5 inflammasomes. Importantly, L. pneumophila infects hemocytes of the invertebrate Galleria mellonella, kill G. mellonella larvae, and proliferate in and kill Drosophila adult flies and Caenorhabditis elegans. Although co-evolution with protist hosts has provided a substantial blueprint for L. pneumophila to infect macrophages, we discuss the further evolutionary aspects of co-evolution of L. pneumophila and its adaptation to modulate various highly evolved innate metazoan processes prior to becoming a human pathogen.

Nutrition and Bipartite Metabolism of Intracellular Pathogens

“…Why L. pneumophila prefers amino acids over glucose, like most other genera of bacteria studied, is unknown. The answer likely lies within its genome and through better understanding of its evolution with protist hosts [19,20]. Like most driving factors for coevolution, use of amino acids could keep it reliant on its host, limiting growth only when within a host, thus giving L. pneumophila an evolutionary advantage.…”

Comprehensive Comparative Genomics Reveals Over 50 Phyla of Free-living and Pathogenic Bacteria are Associated with Diverse Members of the Amoebozoa

“…In facultative associations, the pathogenic bacteria can use the amoeba cell as a safe niche to reproduce, or intermediate host, or even as a vehicle for dispersal or population reservoir 4,21 . Some recent studies have proposed that amoebozoans could serve as an ‘interim training ground’ to develop intracellular survival strategies before becoming a human pathogen due to the similarity in mechanism of phagocytosis (phagolysosome) within mammalian macrophages 4,16,27 Most of the known pathogenic bacteria associated with Amoebozoa so far come from the studies that used only a few amoebozoan species, which are not necessarily reflective of pathogens that can be harbored by various groups in the supergroup of Amoebozoa. In this study, we discovered 49 pathogenic bacterial genera belonging to 9 phyla, the highest report so far (Table 1).…”

“…Amoebozoans have been implicated as training ground for emerging pathogens and vehicles for their dispersal 4,20 . These studies also gave insights on mechanism of pathogen evasion and host defense 16,20,26,31 . Despite these major advances in the field, the number of amoebozoans examined for association with bacteria remain limited; and the studied lineages are not representative of the extremely diverse groups currently recognized within the supergroup.…”

The manipulation of host transcription by the ANKH effector of legionella.

“…AnkH is one of a few of the ~330 Legionella effectors required for intracellular growth within amoebae hosts and human macrophages [192,210]. To get more insight into possible cellular function of AnkH, we have determined its three-dimensional crystal structure.…”

“…Legionella pneumophila is a Gram-negative intracellular pathogen that is ubiquitous in freshwater environments [189] where it primarily parasitizes a wide range of protozoan hosts, which serve as the bacterial natural hosts [40,190,191] and contribute to pathogenesis and ecology of the pathogen [4,50,65,192]. When humans encounter contaminated water sources, aerosolized water droplets can be inhaled and reach the lung where bacteria can invade and proliferate within alveolar macrophages, causing pneumonia [193].…”