Flagella are a positive predictor for virulence inLegionella

Bosshardt, Stephen C.; Benson, Robert F.; Fields, Barry S.

doi:10.1006/mpat.1997.0134

Cited by 26 publications

(21 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Also, the finding that flagellar expression is not required for the intraperitoneal infection of guinea pigs argues against the involvment of flagella in virulence (12). Due to this conflicting results, other authors have suggested that Legionella virulence factors may be coregulated with flagellar expression (6).…”

Section: Discussionmentioning

confidence: 99%

“…Motility-defective bacteria of some species have been reported to be affected in virulence because of aberrations in host cell adherence, invasion mechanisms, or other unknown factors (10,14,35,36). Previous studies utilizing insertional mutagenesis have linked the expression of flagella by L. pneumophila and the ability of this pathogen to infect A. castellanii, H. vermiformis, and human U937 cells (6,38). Moreover, flagellated legionellae have been found in lung alveolar spaces of legionellosis patients (9).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we demonstrated that the expression of the flaA gene is regulated at the transcriptional level (24) by the alternative 28 factor (FliA) and probably by FlaR, a regulator of the LysR family (25). Moreover, the complex flagellum expression and assembly seems to be coordinatively regulated with other virulence-associated traits (6,16,38,40). These traits include thickening of the cell envelope, sensitivity to NaCl, contact-dependent cytotoxicity, osmotic resistance, and evasion of macrophage lysosomes (8).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Flagellum of Legionella pneumophila Positively Affects the Early Phase of Infection of Eukaryotic Host Cells

et al. 2001

View full text Add to dashboard Cite

Legionella pneumophila, the etiologic agent of Legionnaires' disease, contains a single, monopolar flagellum which is composed of one major subunit, the FlaA protein. To evaluate the role of the flagellum in the pathogenesis and ecology of Legionella, the flaA gene of L. pneumophila Corby was mutagenized by introduction of a kanamycin resistance cassette. Immunoblots with antiflagellin-specific polyclonal antiserum, electron microscopy, and motility assays confirmed that the specific flagellar mutant L. pneumophila Corby KH3 was nonflagellated. The redelivery of the intact flaA gene into the chromosome (L. pneumophila Corby CD10) completely restored flagellation and motility. Coculture studies showed that the invasion efficiency of the flaA mutant was moderately reduced in amoebae and severely reduced in HL-60 cells. In contrast, adhesion and the intracellular rate of replication remained unaffected. Taking these results together, we have demonstrated that the flagellum of L. pneumophila positively affects the establishment of infection by facilitating the encounter of the host cell as well as by enhancing the invasion capacity.Legionella pneumophila, the etiologic agent of Legionnaires' disease, is a ubiquitous microorganism inhabiting natural and man-made freshwater biotopes (5). In these environments, the gram-negative, rod-shaped bacteria survive as intracellular pathogens of protozoan organisms such as Acanthamoeba castellanii, Hartmannella vermiformis, and Naegleria spp. (15). Upon transmission to individuals via L. pneumophila-containing aerosols generated by showerheads and air-conditioning systems, the bacteria invade and multiply within alveolar macrophages (1, 2, 7) and nonphagocytic cells (17). The infection which mainly affects immunocompromised patients results in a life-threatening atypical pneumonia (7).Detailed ultrastructural and molecular studies of the intracellular fate of the bacterium revealed that human macrophages and protozoan cells infected with L. pneumophila exhibit remarkable similarities concerning the establishment of a replicative phagosome (3,16,22,42,45). However, significant differences were observed during early stages of infection (21). Uptake by Hartmannella is accomplished by a microfilamentindependent mechanism that is sensitive to methylamine, which is an inhibitor of receptor-mediated endocytosis (28). So far, one receptor of Hartmanella vermiformis, a Gal/GalNAc lectin, could be identified (46). Attachment of L. pneumophila to this lectin results in tyrosine dephosphorylation of multiple host cell proteins. However, depending on the type of amoeba, different receptors might be involved (22). In contrast, the uptake by human macrophages occurs following binding of complement receptors CR1 and CR3 via microfilament-dependent phagocytosis (26). In addition to this cytochalasin D-sensitive mechanism, complement-independent mechanisms for uptake by nonphagocytic cells have been described (39).The influence of bacterial motility on infection processes or on survival of legio...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Flagellum of Legionella pneumophila Positively Affects the Early Phase of Infection of Eukaryotic Host Cells

et al. 2001

View full text Add to dashboard Cite

show abstract

“…It has been suggested that the virulence of C. difficile strains is Clostridium difficile flagellin not solely attributable to toxin production ; other factors such as presence of flagella could contribute to virulence. The role of flagella in microbial pathogenesis factors such as virulence, adherence, invasiveness or colonization has been demonstrated for numerous bacteria (Grant et al, 1993 ;Scherer et al, 1993 ;Zhang et al, 1993 ;Grossman et al, 1995 ;Pruckler et al, 1995 ;Tamura et al, 1995 ;Milton et al, 1996 ;Mobley, 1996 ;Bosshardt et al, 1997 ;Kennedy et al, 1997 ;Rosalski et al, 1997 ;West et al, 1997 ;Feldman et al, 1998). In our experiments in vitro, no inhibition of adherence was shown with antibodies against the recombinant flagellum subunit.…”

Section: Discussionmentioning

confidence: 99%

A Clostridium difficile gene encoding flagellin The GenBank accession numbers for the sequences reported in this paper are AF065259 (strain 79-685) and AF077341 (strain VPI 10463).

et al. 2000

View full text Add to dashboard Cite

“…On the other hand, it has been shown that the flagellar system is needed for full fitness of L. pneumophila (20). Furthermore, it is known that the complex flagellar regulon is coordinately regulated with the expression of other virulence-associated factors (4,6,20,32). Studies in our laboratory have demonstrated that the flaA gene (encoding the major subunit flagellin) is positively regulated by the alternative 28 factor (FliA) and seems to be negatively regulated by the transcriptional regulator FlaR (16,18,20).…”

mentioning

confidence: 99%

Characterization of the Alternative Sigma Factor σ ⁵⁴ and the Transcriptional Regulator FleQ of Legionella pneumophila , Which Are Both Involved in the Regulation Cascade of Flagellar Gene Expression

2004

View full text Add to dashboard Cite

Legionella pneumophila, the causative agent of Legionnaires' disease, is a ubiquitous microorganism inhabiting man-made water systems and freshwater biotopes. Legionella infection occurs after inhalation of aerosolized bacteria. The organism invades and proliferates in alveolar macrophages of the human lung. In the environment, Legionella replicates intracellularly in amoebae and other protozoans (13).Previous studies have demonstrated that the flagellum positively affects the establishment of infection but is not required for intracellular replication (9, 28). On the other hand, it has been shown that the flagellar system is needed for full fitness of L. pneumophila (20). Furthermore, it is known that the complex flagellar regulon is coordinately regulated with the expression of other virulence-associated factors (4,6,20,32). Studies in our laboratory have demonstrated that the flaA gene (encoding the major subunit flagellin) is positively regulated by the alternative 28 factor (FliA) and seems to be negatively regulated by the transcriptional regulator FlaR (16,18,20). Furthermore, flaA expression is modulated by various environmental factors (17); for a review see reference 21).Genome analysis revealed the presence of putative 54 promoter sites upstream of most of the flagellar operons, and we hypothesized that RpoN and FleQ may regulate these operons (21). For Pseudomonas aeruginosa it has been shown that 54 and a factor containing a 54 interaction domain are at the top of the cascade of flagellar gene regulation (2,7,8,25). In order to obtain support for our hypothesis and to further characterize the cascade of flagellar gene expression, we screened the genome sequence of L. pneumophila for a homolog of rpoN and for factors having a 54 interaction domain. In this paper we describe identification of the 54 factor and the transcriptional regulator FleQ and the role of this factor and this regulator in flagellar gene regulation in L. pneumophila. MATERIALS AND METHODSL. pneumophila Corby serogroup 1 (S1) (22) was used to clone the rpoN and fleQ genes. The legionellae used in a Southern blot analysis were L. pneumophila (3), L. pneumophila type strains (S7, S10, S12, and S13) (P. C. Lück, Dresden, Germany), L. pneumophila Bloomington (ϭ ATCC 33155) (S3), L. pneumophila Los Angeles (ϭ ATCC 33156) (S4), L. pneumophila Chicago-2 (ϭ ATCC 33215) (S6), Legionella anisa (12), Legionella bozemanii ATCC 33217, Legionella dumoffii ATCC 33279, Legionella feelei ATCC 35072 (S1), Legionella gormanii ATCC 33297, Legionella hackeliae ATCC 33250 and ATCC 35999 (S1 and S2), Legionella israeliensis ATCC 43119, Legionella jordanis ATCC 33623, Legionella longbeachae ATCC 33462 and ATCC 33484 (S1 and S2), Legionella micdadei ATCC 33218, Legionella oakridgensis ATCC 33761, Legionella erythra (34), and Sarcobium (Legionella) lyticum PCM 2298 (Polish Culture of Microorganisms). Escherichia coli DH5␣ was used for cloning of recombinant plasmid DNA. Plasmid pUC18 or pUC19 (Pharmacia LKB, Freiburg, Germany) was used for subcloning of ...

show abstract

Flagella are a positive predictor for virulence inLegionella

Cited by 26 publications

References 20 publications

Flagellum of Legionella pneumophila Positively Affects the Early Phase of Infection of Eukaryotic Host Cells

Flagellum of Legionella pneumophila Positively Affects the Early Phase of Infection of Eukaryotic Host Cells

A Clostridium difficile gene encoding flagellin The GenBank accession numbers for the sequences reported in this paper are AF065259 (strain 79-685) and AF077341 (strain VPI 10463).

Characterization of the Alternative Sigma Factor σ ⁵⁴ and the Transcriptional Regulator FleQ of Legionella pneumophila , Which Are Both Involved in the Regulation Cascade of Flagellar Gene Expression

Contact Info

Product

Resources

About

Flagella are a positive predictor for virulence inLegionella

Cited by 26 publications

References 20 publications

Flagellum of Legionella pneumophila Positively Affects the Early Phase of Infection of Eukaryotic Host Cells

Flagellum of Legionella pneumophila Positively Affects the Early Phase of Infection of Eukaryotic Host Cells

A Clostridium difficile gene encoding flagellin The GenBank accession numbers for the sequences reported in this paper are AF065259 (strain 79-685) and AF077341 (strain VPI 10463).

Characterization of the Alternative Sigma Factor σ 54 and the Transcriptional Regulator FleQ of Legionella pneumophila , Which Are Both Involved in the Regulation Cascade of Flagellar Gene Expression

Contact Info

Product

Resources

About

Characterization of the Alternative Sigma Factor σ ⁵⁴ and the Transcriptional Regulator FleQ of Legionella pneumophila , Which Are Both Involved in the Regulation Cascade of Flagellar Gene Expression