Legionella Phospholipases Implicated in Virulence

Abstract

Phospholipases are diverse enzymes produced in eukaryotic hosts and their bacterial pathogens. Several pathogen phospholipases have been identified as major virulence factors acting mainly in two different modes: on the one hand, they have the capability to destroy host membranes and on the other hand they are able to manipulate host signaling pathways. Reaction products of bacterial phospholipases may act as secondary messengers within the host and therefore influence inflammatory cascades and cellular processes, such as proliferation, migration, cytoskeletal changes as well as membrane traffic. The lung pathogen and intracellularly replicating bacterium Legionella pneumophila expresses a variety of phospholipases potentially involved in disease-promoting processes. So far, genes encoding 15 phospholipases A, three phospholipases C, and one phospholipase D have been identified. These cell-associated or secreted phospholipases may contribute to intracellular establishment, to egress of the pathogen from the host cell, and to the observed lung pathology. Due to the importance of phospholipase activities for host cell processes, it is conceivable that the pathogen enzymes may mimic or substitute host cell phospholipases to drive processes for the pathogen's benefit. The following chapter summarizes the current knowledge on the L. pneumophila phospholipases, especially their substrate specificity, localization, mode of secretion, and impact on host cells.

Oligomerization Inhibits Legionella pneumophila PlaB Phospholipase A Activity

“…Legionella pneumophila, an important intracellular lung pathogen that primarily thrives in environmental amoebae, possesses a variety of phospholipases (1)(2)(3). So far, phospholipases A (PLA) 2 /lysophospholipases A (LPLA) comprising 15 different proteins are the most prominent ones, although three additional phospholipases C and one phospholipase D have been described (1,2,4,5).…”

Bacterial Sphingomyelinases and Phospholipases as Virulence Factors

“…This bacterium is ubiquitous to the environment, and in humans it is an opportunistic pathogen that causes Legionnaires' disease, a severe pneumonia frequently accompanied by acute respiratory distress syndrome (81). L. pneumophila possesses a large variety of about 20 established and potential PLAs (15 enzymes), PLCs (3 enzymes), and PLDs (1 enzyme) (82,83). L. pneumophila PLase activity destroys phospholipids from lung surfactant, which cov- ers small airways, bronchioles, and the alveolar surface and reduces the surface tension, and thereby its activity may contribute to lung disease (84).…”

“…L. pneumophila PLase activity destroys phospholipids from lung surfactant, which cov- ers small airways, bronchioles, and the alveolar surface and reduces the surface tension, and thereby its activity may contribute to lung disease (84). The most prominent PLA activity of L. pneumophila is PlaB (Table 4) (83).…”

“…pneumophila encodes 11 patatin-like PLases, designated VipD/PatA, PatB, VpdA/PatC, PatD, PatE, VpdC/PatF, VpdB/ PatG, and PatH to PatK (83). VipD, VpdA, VdpB, and VpdC are translocated by the Dot/Icm type IVB secretion system into the host cell (164)(165)(166).…”

Phospholipases during membrane dynamics in malaria parasites

“…reviewed in Côtes et al, 2008;Djordjevic, 2010;Flores-Díaz et al, 2016;Kuhle and Flieger, 2013;van der Meer-Janssen et al, 2010), surprisingly the phospholipases of malaria parasites as mediators of biomembrane dynamics are hitherto under-investigated. Notwithstanding the limited number of studies that have addressed phospholipase functions to date, they revealed critical roles for these PLhydrolyzing enzymes during the Plasmodium life-cycle.…”