The role of protein secretion systems in the virulence of the intracellular pathogen Legionella pneumophila

Buck, Emmy De; Anné, Jozef; Lammertyn, Elke

doi:10.1099/mic.0.2007/012039-0

Cited by 33 publications

(33 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gram-negative bacterial pathogens and endosymbionts use these specialized secretion systems to transport toxins and effectors to the extracellular environment or directly into the host cell to modify host physiology and promote interactions (91). It has been established that type II and type IVB secretion systems are essential for L. pneumophila virulence (25). Genes encoding type I, II, IVA, and IVB secretion system homologs were also found in the D-4968 genome, but there were several noteworthy differences.…”

Section: Resultsmentioning

confidence: 99%

“…L. pneumophila genomes encode multiple protein secretion systems, including the putative type I Lss secretion machinery, type II PilD-dependent Lsp, type IVA Lvh, and type IVB Icm/Dot, as well as a putative type V secretion pathway (25). Gram-negative bacterial pathogens and endosymbionts use these specialized secretion systems to transport toxins and effectors to the extracellular environment or directly into the host cell to modify host physiology and promote interactions (91).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Virulence Factors Encoded by Legionella longbeachae Identified on the Basis of the Genome Sequence Analysis of Clinical Isolate D-4968

et al. 2010

View full text Add to dashboard Cite

Legionella longbeachae causes most cases of legionellosis in Australia and may be underreported worldwide due to the lack of L. longbeachae-specific diagnostic tests. L. longbeachae displays distinctive differences in intracellular trafficking, caspase 1 activation, and infection in mouse models compared to Legionella pneumophila, yet these two species have indistinguishable clinical presentations in humans. Unlike other legionellae, which inhabit freshwater systems, L. longbeachae is found predominantly in moist soil. In this study, we

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Virulence Factors Encoded by Legionella longbeachae Identified on the Basis of the Genome Sequence Analysis of Clinical Isolate D-4968

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The reticulate bodies replicate within the expanding inclusion membrane for approximately 2 to 3 days, differentiate back to elementary bodies, and are released extracellularly (for review, see Dautry-Varsat et al 10 ). L pneumophila is a facultative intracellular pathogen that is internalized into a phagosome that remains separated from lysosomes, but recruits endoplasmic reticulum-derived vesicles for the expanding phagosomal membrane and mitochondria for nutrients (for review, see De Buck et al 11 ). Both Chlamydia and Legionella require iron for replication and expansion.…”

Section: Introductionmentioning

confidence: 99%

Iron depletion limits intracellular bacterial growth in macrophages

Paradkar

Domenico

Durchfort

et al. 2008

Blood

188

166

View full text Add to dashboard Cite

Many intracellular pathogens infect macrophages and these pathogens require iron for growth. Here we demonstrate in vitro that the intracellular growth of Chlamydia psittaci, trachomatis, and Legionella pneumophila is regulated by the levels of intracellular iron. Macrophages that express cell surface ferroportin, the only known cellular iron exporter, limit the intracellular growth of these bacteria.Hepcidin is an antimicrobial peptide secreted by the liver in response to inflammation. Hepcidin binds to ferroportin mediating its internalization and degradation. Addition of hepcidin to infected macrophages enhanced the intracellular growth of these pathogens. Macrophages from flatiron mice, a strain heterozygous for a loss-of-function ferroportin mutation, showed enhanced intracellular bacterial growth independent of the presence of exogenous hepcidin. Macrophages, from wild-type or flatiron mice, incubated with the oral iron chelator deferriprone or desferasirox showed reduced intracellular bacterial growth suggesting that these chelators might be therapeutic in chronic intracellular bacterial infections. (Blood. 2008;112:866-874) IntroductionHypoferremia is a hallmark of inflammation and results from increased secretion of the liver hormone hepcidin (for review, see Nemeth and Ganz 1 ). Hepcidin is secreted by hepatocytes in response to inflammatory stimuli, notably interleuklin-6 (IL-6). [2][3][4] Hepcidin binds to the iron exporter ferroportin (Fpn), leading to its internalization and degradation. 5 Fpn is the only identified cellular iron exporter and is present on macrophages, absorptive enterocytes, and placenta. Loss of cell surface Fpn results in hypoferremia, which, if persistent, leads to iron-limited erythropoiesis. 6 The hypoferremia of inflammation is thought to represent an antibacterial defense response, as iron acquisition proteins are virulence factors for many species of bacteria. 7 The loss of cell surface Fpn also leads to increased cellular iron, particularly in macrophages that are continuously obtaining iron from senescent red blood cells. The hypoferremia of inflammation may limit the growth of extracellular bacteria but may promote the growth of intracellular bacteria. Support for this hypothesis has been suggested by studies in Salmonellainfected macrophages, where addition of hepcidin promoted the growth of bacteria. 8,9 We show that the growth of 3 other species of intracellular bacteria, Chlamydia psittaci, C trachomatis, and Legionella pneumophila, is promoted by hepcidin-mediated down-regulation of Fpn. Chlamydia spp are obligate intracellular pathogens that have a unique developmental cycle. The infectious forms of Chlamydia spp are termed elementary bodies. After infecting host cells, the elementary bodies differentiate (2-4 hours) within the inclusion membrane to the metabolically active bacteria, termed reticulate bodies, which are noninfectious. The reticulate bodies replicate within the expanding inclusion membrane for approximately 2 to 3 days, differentiate back to element...

show abstract

“…Within the mammalian lung, the organism has the ability to attach to and invade macrophages and epithelia (27,106,113). Among the processes that promote L. pneumophila growth in both the environment and the mammalian lung are Lsp type II protein secretion, Dot/Icm type IVB protein secretion, and Lvh type IVA protein secretion (5,25,31,106). Other key surface features of L. pneumophila are polar flagella that promote swimming motility and type IV pili that help mediate adherence (53,103,113).…”

mentioning

confidence: 99%

Surface Translocation byLegionella pneumophila: a Form of Sliding Motility That Is Dependent upon Type II Protein Secretion

2009

View full text Add to dashboard Cite

Legionella pneumophila exhibits surface translocation when it is grown on a buffered charcoal yeast extract (BCYE) containing 0.5 to 1.0% agar. After 7 to 22 days of incubation, spreading legionellae appear in an amorphous, lobed pattern that is most manifest at 25 to 30°C. All nine L. pneumophila strains examined displayed the phenotype. Surface translocation was also exhibited by some, but not all, other Legionella species examined. L. pneumophila mutants that were lacking flagella and/or type IV pili behaved as the wild type did when plated on low-percentage agar, indicating that the surface translocation is not swarming or twitching motility. A translucent film was visible atop the BCYE agar, advancing ahead of the spreading legionellae. Based on its abilities to disperse water droplets and to promote the spreading of heterologous bacteria, the film appeared to manipulate surface tension and, as such, acted like a surfactant. Indeed, a sample obtained from the film rapidly dispersed when it was spotted onto a plastic surface. L. pneumophila type II secretion (Lsp) mutants, but not their complemented derivatives, were defective for both surface translocation and film production. In contrast, mutants defective for type IV secretion exhibited normal surface translocation. When lsp mutants were spotted onto film produced by the wild type, they were able to spread, suggesting that type II secretion promotes the elaboration of the Legionella surfactant. Together, these data indicate that L. pneumophila exhibits a form of surface translocation that is most akin to "sliding motility" and uniquely dependent upon type II secretion.The genus Legionella was established in 1977, following the isolation of Legionella pneumophila from patients with a form of pneumonia now known as Legionnaires' disease (33). Today, L. pneumophila is recognized as a common cause of both community-acquired and nosocomial pneumonia (84). Legionellosis occurs sporadically and in large outbreaks, with the largest outbreak occurring as recently as 2003 and encompassing 800 suspected and 449 confirmed cases (43). L. pneumophila is especially pathogenic for the elderly and the immunocompromised, large and growing segments of the population (39, 84), and recent studies have been highlighting the growing significance of travel-associated Legionnaires' disease (107). L. pneumophila is a gram-negative, gammaproteobacterium that is widespread in natural and manufactured water systems (22,39,93). Infection occurs after the inhalation of Legionellacontaminated water droplets originating from a wide variety of aerosol-generating devices (39). Alarmingly, outbreaks can occur following the airborne spread of L. pneumophila over distances of Ͼ10 km from cooling towers or scrubbers (86). Within its aquatic habitats, L. pneumophila survives over a wide temperature range and grows on surfaces, in biofilms, and as an intracellular parasite of protozoa (9,39,110). Within the mammalian lung, the organism has the ability to attach to and invade macrophages and epit...

show abstract

The role of protein secretion systems in the virulence of the intracellular pathogen Legionella pneumophila

Cited by 33 publications

References 32 publications

Virulence Factors Encoded by Legionella longbeachae Identified on the Basis of the Genome Sequence Analysis of Clinical Isolate D-4968

Virulence Factors Encoded by Legionella longbeachae Identified on the Basis of the Genome Sequence Analysis of Clinical Isolate D-4968

Iron depletion limits intracellular bacterial growth in macrophages

Surface Translocation byLegionella pneumophila: a Form of Sliding Motility That Is Dependent upon Type II Protein Secretion

Contact Info

Product

Resources

About