Impact of Non-Legionella Bacteria on the Uptake and Intracellular Replication of Legionella pneumophila in Acanthamoeba castellanii and Naegleria lovaniensis

Declerck, Priscilla; Behets, Jonas; Delaedt, Yasmine; Margineanu, Anca; Lammertyn, Elke; Ollevier, Frans

doi:10.1007/s00248-005-0258-0

Cited by 59 publications

(57 citation statements)

References 23 publications

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“…L. pneumophila infects at least seven genera and 17 species of protozoa (28,67) and, therefore, it is reasonable to think that certain bacterial factors might have evolved to have greater importance in only certain protozoa. Previous studies have found that the growth and uptake of wild-type L. pneumophila can vary between Acanthamoeba, Hartmannella, and Naegleria hosts (24,38,55,71). But, few past studies have examined specific mutants of L. pneumophila for their capacity to infect multiple protozoa (55,77).…”

Section: Discussionmentioning

confidence: 99%

The Type II Secretion System ofLegionella pneumophilaElaborates Two Aminopeptidases, as Well as a Metalloprotease That Contributes to Differential Infection among Protozoan Hosts

Rossier

Dao

Cianciotto

2008

Appl Environ Microbiol

109

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Legionella pneumophila, the agent of Legionnaires' disease, is an intracellular parasite of aquatic amoebae and human macrophages. A key factor for L. pneumophila in intracellular infection is its type II protein secretion system (Lsp). In order to more completely define Lsp output, we recently performed a proteomic analysis of culture supernatants. Based upon the predictions of that analysis, we found that L. pneumophila secretes two distinct aminopeptidase activities encoded by the genes lapA and lapB. Whereas lapA conferred activity against leucine, phenylalanine, and tyrosine aminopeptides, lapB was linked to the cleavage of lysineand arginine-containing substrates. To assess the role of secreted aminopeptidases in intracellular infection, we examined the relative abilities of lapA and lapB mutants to infect human U937 cell macrophages as well as Hartmannella vermiformis and Acanthamoeba castellanii amoebae. Although these experiments identified a dispensable role for LapA and LapB, they uncovered a previously unrecognized role for the type II-dependent ProA (MspA) metalloprotease. Whereas proA mutants were not defective for macrophage or A. castellanii infection, they (but not their complemented derivatives) were impaired for growth upon coculture with H. vermiformis. Thus, ProA represents the first type II effector implicated in an intracellular infection event. Furthermore, proA represents an L. pneumophila gene that shows differential importance among protozoan infection models, suggesting that the legionellae might have evolved some of its factors to especially target certain of their protozoan hosts.Legionella pneumophila is the agent of Legionnaires' disease pneumonia (29). In fresh waters, this gram-negative bacterium exists in protozoan hosts and as a part of biofilms. Disease occurs when inhaled legionellae, possibly including those still associated with protozoa or protozoan vesicles (11, 12), invade alveolar macrophages. Although many factors promote the ecology and pathogenesis of L. pneumophila, protein secretion stands out for its multifaceted significance. L. pneumophila possesses type II secretion, type IVB secretion, and type IVA secretion (7, 17), and genome sequencing suggests the existence of type I and type V secretion systems (14,40). Among these pathways, the Lsp type II system is arguably implicated in the broadest array of phenotypes (17). Indeed, this pathway is required for secretion during growth in bacteriologic media at 37°C, extracellular survival in broth/water at 12 to 25°C, colony morphology, intracellular infection of protozoa (acanthamoebae and hartmannellae), optimal intracellular infection of human macrophages and monocytes, and virulence in a murine model of pneumonia (37,44,55,61,62,68,69). Although type II secretion exists in many gram-negative organisms, including various animal and plant pathogens, L. pneumophila is the only intracellular pathogen known to possess a functional type II system (17). Type II secretion is a two-step process in which nascent proteins ar...

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Section: Discussionmentioning

confidence: 99%

The Type II Secretion System ofLegionella pneumophilaElaborates Two Aminopeptidases, as Well as a Metalloprotease That Contributes to Differential Infection among Protozoan Hosts

Rossier

Dao

Cianciotto

2008

Appl Environ Microbiol

109

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“…To assess L. pneumophila growth within mammalian cells, we infected human U937 macrophages (ATCC CRL-1593.2) as previously done (7). To examine the ability of L. pneumophila strains to grow in protozoa, A. castellanii (ATCC 30234), H. vermiformis (ATCC 50237), and Naegleria lovaniensis (ATCC 30569) were infected as described previously (19,27,30,43,44). H. vermiformis and N. lovaniensis were infected in ATCC medium number 1034 that lacked its serum component, whereas infection of A. castellanii utilized protease peptone-yeast extract (PY) medium.…”

Section: Methodsmentioning

confidence: 99%

Multiple Legionella pneumophila Type II Secretion Substrates, Including a Novel Protein, Contribute to Differential Infection of the Amoebae Acanthamoeba castellanii, Hartmannella vermiformis, and Naegleria lovaniensis

et al. 2013

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Type II protein secretion (T2S) by Legionella pneumophila is required for intracellular infection of host cells, including macrophages and the amoebae Acanthamoeba castellanii and Hartmannella vermiformis. Previous proteomic analysis revealed that T2S by L. pneumophila 130b mediates the export of >25 proteins, including several that appeared to be novel. Following confirmation that they are unlike known proteins, T2S substrates NttA, NttB, and LegP were targeted for mutation. nttA mutants were impaired for intracellular multiplication in A. castellanii but not H. vermiformis or macrophages, suggesting that novel exoproteins which are specific to Legionella are especially important for infection. Because the importance of NttA was host cell dependent, we examined a panel of T2S substrate mutants that had not been tested before in more than one amoeba. As a result, RNase SrnA, acyltransferase PlaC, and metalloprotease ProA all proved to be required for optimal intracellular multiplication in H. vermiformis but not A. castellanii. Further examination of an lspF mutant lacking the T2S apparatus documented that T2S is also critical for infection of the amoeba Naegleria lovaniensis. Mutants lacking SrnA, PlaC, or ProA, but not those deficient for NttA, were defective in N. lovaniensis. Based upon analysis of a double mutant lacking PlaC and ProA, the role of ProA in H. vermiformis was connected to its ability to activate PlaC, whereas in N. lovaniensis, ProA appeared to have multiple functions. Together, these data document that the T2S system exports multiple effectors, including a novel one, which contribute in different ways to the broad host range of L. pneumophila.

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“…These results highlight Naegleria as a useful host for the replication and distribution of L. pneumophila (268). Bacterial attachment and uptake occurs through a receptor-mediated endocytosis, which requires de novo synthesis of host proteins.…”

Section: Host For Other Microbesmentioning

confidence: 85%

Biology and pathogenesis of Naegleria fowleri

et al. 2016

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2 SummaryNaegleria fowleri is a protist pathogen that can cause lethal brain infection. Despite decades of research, the mortality rate related with primary amoebic meningoencephalitis owing to N. fowleri remains more than 90%. The amoebae pass through the nose to enter the central nervous system killing the host within days, making it one of the deadliest opportunistic parasites. Accordingly, we present an up to date review of the biology and pathogenesis of N.fowleri and discuss needs for future research against this fatal infection.

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Impact of Non-Legionella Bacteria on the Uptake and Intracellular Replication of Legionella pneumophila in Acanthamoeba castellanii and Naegleria lovaniensis

Cited by 59 publications

References 23 publications

The Type II Secretion System ofLegionella pneumophilaElaborates Two Aminopeptidases, as Well as a Metalloprotease That Contributes to Differential Infection among Protozoan Hosts

The Type II Secretion System ofLegionella pneumophilaElaborates Two Aminopeptidases, as Well as a Metalloprotease That Contributes to Differential Infection among Protozoan Hosts

Multiple Legionella pneumophila Type II Secretion Substrates, Including a Novel Protein, Contribute to Differential Infection of the Amoebae Acanthamoeba castellanii, Hartmannella vermiformis, and Naegleria lovaniensis

Biology and pathogenesis of Naegleria fowleri

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