Infectivity of Legionella pneumophila mip mutant for alveolar epithelial cells

Cianciotto, Nicholas P.; Stamos, Julie Kim; Kamp, David W.

doi:10.1007/bf00293641

Cited by 67 publications

(56 citation statements)

References 18 publications

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“…This hypothesis is supported by the fact that proteins exhibiting PPIase activity such as the Mip of L. pneumophila are involved in virulence. Mip-negative mutants were less infective for Hartmannella vermiformis and lung epithelial cells (22,23). Proteins with PPIase activity were also identified in other microorganisms such as Chlamydia trachomatis (60), Chlamydia psittaci (61), Coxiella burnetti (62), Trypanozoma cruzi (63), and E. coli (64).…”

Section: Discussionmentioning

confidence: 98%

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The Streptococcal Lipoprotein Rotamase A (SlrA) Is a Functional Peptidyl-prolyl Isomerase Involved in Pneumococcal Colonization

Hermans¹,

Adrian

Albert

et al. 2006

Journal of Biological Chemistry

109

119

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Streptococcus pneumoniae expresses two surface-exposed lipoproteins, PpmA and SlrA, which share homology with distinct families of peptidyl-prolyl isomerases (PPIases). In this study, we demonstrated for the first time that the lipoprotein cyclophilin, SlrA, can catalyze the cis-trans isomerization of proline containing tetrapeptides and that SlrA contributes to pneumococcal colonization. The substrate specificity of SlrA is typical for prokaryotic and eukaryotic cyclophilins, with Suc-Ala-AlaPro-Phe-p-nitroanilide (pNA) being the most rapidly catalyzed substrate. In a mouse pneumonia model the slrA knock-out D39⌬slrA did not cause significant differences in the survival times of mice compared with the isogenic wild-type strain. In contrast, a detailed analysis of bacterial outgrowth over time in the nasopharynx, airways, lungs, blood, and spleen showed a rapid elimination of slrA mutants from the upper airways but did not reveal significant differences in the lungs, blood, and spleen. These results suggested that SlrA is involved in colonization but does not contribute significantly to invasive pneumococcal disease. In cell culture infection experiments, the absence of SlrA impaired adherence to pneumococcal disease-specific epithelial and endothelial non-professional cell lines. Adherence of the slrA mutant could not be restored by exogenously added SlrA. Strikingly, deficiency in SlrA did not reduce binding activity to host target proteins, but resulted in enhanced uptake by professional phagocytes. In conclusion, SlrA is a functional, cyclophilin-type PPIase and contributes to pneumococcal virulence in the first stage of infection, namely, colonization of the upper airways, most likely by modulating the biological function of important virulence proteins. Peptidyl-prolyl cis/trans isomerases (PPIases)6 are ubiquitous foldases, which accelerate the rate-limiting cis-trans or trans-cis conformational changes at Xaa-Pro bonds during protein folding in both eukaryotes and prokaryotes. There are three distinct families within the enzyme class of PPIases (EC 5.2.1.8): the cyclophilins, which bind the immunosuppressant cyclosporin A, the FK506-binding proteins, and the parvulins. The classical PPIase such as rotamase A of Escherichia coli is a member of the cyclophilin family (1, 2). The FK506-binding proteins all have high affinity for the immunosuppressant drug FK506 (3, 4). The ubiquitous bacterial trigger factor (5, 6) and the macrophage infectivity potentiator (Mip) protein of Legionella pneumophila (7) belong to the FK506-binding proteins. The parvulin family resembles enzymes such as parvulin, SurA, and PrsA. The E. coli parvulin 10 with its 92 amino acids is one of the smallest known PPIase enzymes and represents the prototype of this family (8). SurA contributes to the assembly of outer membrane proteins in Gram-negative bacteria (9). PrsA is considered to be involved in enzyme secretion and activation in Gram-positive bacteria (10 -12).Streptococcus pneumoniae (the pneumococcus) is a frequent colonizer of...

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Section: Discussionmentioning

confidence: 98%

“…For example, the Mip protein of L. pneumophila is involved in entry of host cells and intracellular replication (22)(23)(24)(25), and the trigger factor of Streptococcus pyogenes is considered to be responsible for secretion of several virulence factors (26).…”

mentioning

confidence: 99%

The Streptococcal Lipoprotein Rotamase A (SlrA) Is a Functional Peptidyl-prolyl Isomerase Involved in Pneumococcal Colonization

Hermans¹,

Adrian

Albert

et al. 2006

Journal of Biological Chemistry

109

119

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“…L. pneumophila constitutes a broad relatedness group, however, so detection of a representative of the group does not indicate a pathogen. Because of the potential human health implication of this detection, we conducted quantitative PCR (QPCR) assays with a L. pneumophila-specific primer pair that targets a pathogenesis gene, the macrophage infectivity potentiator (mip) gene (20)(21)(22)(23)(24), to screen a subset of samples. Thirty-six samples (16 water and 20 swabs, representing 10 cities) were tested in duplicate reactions, including samples with positive L. pneumophila detection by sequence.…”

Section: Regionmentioning

confidence: 99%

Opportunistic pathogens enriched in showerhead biofilms

Feazel

Baumgartner²,

Peterson³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

485

364

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The environments we humans encounter daily are sources of exposure to diverse microbial communities, some of potential concern to human health. In this study, we used culture-independent technology to investigate the microbial composition of biofilms inside showerheads as ecological assemblages in the human indoor environment. Showers are an important interface for human interaction with microbes through inhalation of aerosols, and showerhead waters have been implicated in disease. Although opportunistic pathogens commonly are cultured from shower facilities, there is little knowledge of either their prevalence or the nature of other microorganisms that may be delivered during shower usage. To determine the composition of showerhead biofilms and waters, we analyzed rRNA gene sequences from 45 showerhead sites around the United States. We find that variable and complex, but specific, microbial assemblages occur inside showerheads. Particularly striking was the finding that sequences representative of non-tuberculous mycobacteria (NTM) and other opportunistic human pathogens are enriched to high levels in many showerhead biofilms, >100-fold above background water contents. We conclude that showerheads may present a significant potential exposure to aerosolized microbes, including documented opportunistic pathogens. The health risk associated with showerhead microbiota needs investigation in persons with compromised immune or pulmonary systems.bioaerosols ͉ Mycobacterium avium complex ͉ Non-tuberculous mycobacteria ͉ public health ͉ rRNA metagenomics

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“…The ability of L. pneumophila to cause pneumonia is dependent on its capacity to invade and to multiply within the host alveolar phagocytes, and possibly alveolar epithelial cells (Payne and Horwitz, 1987;Horwitz, 1984;1983a,b;Horwitz and Maxfield, 1984;Horwitz and Silverstein, 1980;Cianciotto et al, 1995;Oldham and Rodgers, 1985;Mody et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of the macrophage‐induced gene (gspA) of Legionella pneumophila and phenotypic characterization of a null mutant

Kwaik

Gao

Harb

et al. 1997

Molecular Microbiology

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SummaryExpression of the global stress protein gene (gspA) is induced during the intracellular infection of macrophages and upon exposure of Legionella pneumophila to in vitro stress stimuli. Transcription of gspA is regulated by two promoters, one of which is regulated by the 32 heat-shock transcription factor. We utilized a gspA promoter fusion to a promoterless lacZ to probe the phagososmal 'microenvironment' for the kinetics of exposure of intracellular L. pneumophila to stress stimuli. Expression through the gspA promoter was constitutively induced by approx. 16-fold throughout the intracellular infection, and occurred predominantly through the 32-regulated promoter. Expression of the gspA promoter was induced approx. 4.5-fold, 5-, 11-and 9-fold upon exposure of L. pneumophila to heat shock, oxidative stress, acid shock, and osmotic shock, respectively. An isogenic insertion mutant of L. pneumophila in gspA (strain AA224) was constructed by allelic exchange in the wild-type strain AA200. Compared to in vitrogrown wild-type strain AA200, AA224 was more susceptible to all four in vitro stress stimuli. The wildtype phenotypes were restored to strain AA224 by complementation with a plasmid containing wild-type gspA. There was no difference between the wild-type strain and the gspA mutant in cytopathogenicity to U937 cells or in their kinetics of intracellular replication within macrophages and amoebae. However, compared to in vitro-grown bacteria, macrophage-grown and amoebae-grown AA200 and AA224 showed an equal and dramatic increase in resistance to in vitro stress stimuli. Our data showed that regardless of the capacity of L. pneumophila to subvert the microbicidal mechanisms of the macrophage, intracellular L. pneumophila is exposed to a high level of stress stimuli throughout the intracellular infection. Although the GspA protein is required for protection of the bacteria against in vitro stress stimuli, and is induced during intracellular multiplication, the loss of its function is probably compensated for by other macrophage-induced and stress-induced proteins within the intracellular environment.

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Infectivity of Legionella pneumophila mip mutant for alveolar epithelial cells

Cited by 67 publications

References 18 publications

The Streptococcal Lipoprotein Rotamase A (SlrA) Is a Functional Peptidyl-prolyl Isomerase Involved in Pneumococcal Colonization

The Streptococcal Lipoprotein Rotamase A (SlrA) Is a Functional Peptidyl-prolyl Isomerase Involved in Pneumococcal Colonization

Opportunistic pathogens enriched in showerhead biofilms

Transcriptional regulation of the macrophage‐induced gene (gspA) of Legionella pneumophila and phenotypic characterization of a null mutant

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