LspA inactivation in Mycobacterium tuberculosis results in attenuation without affecting phagosome maturation arrest

Rampini, S; Selchow, Petra; Keller, Christine; Ehlers, Stefan; Böttger, Erik C.; Sander, Peter

doi:10.1099/mic.0.2008/018895-0

Cited by 28 publications

(25 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…by reduced strain survival (15,36,38). The survival of the bacterium is dependent on the ability of the host macrophage to kill and the ability of the bacterium to overcome the killing mechanisms, including interfering with the intricate process of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

et al. 2010

View full text Add to dashboard Cite

Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the causative agent of paratuberculosis, a chronic enteritis of ruminants. To control the considerable economic effect that paratuberculosis has on the livestock industry, a vaccine that induces protection with minimal side effects is required. We employed transposon mutagenesis and allelic exchange to develop three potential vaccine candidates, which were then tested for virulence with macrophages, mice, and goats. All three models identified the WAg906 mutant as being the most attenuated, but some differences in the levels of attenuation were evident among the models when testing the other strains. In a preliminary mouse vaccine experiment, limited protection was induced by WAg915, as evidenced by a reduced bacterial load in spleens and livers 12 weeks following intraperitoneal challenge with M. paratuberculosis K10. While we found macrophages and murine models to be rapid and cost-effective alternatives for the initial screening of M. paratuberculosis mutants for attenuation, it appears necessary to do the definitive assessment of attenuation with a ruminant model.

show abstract

Section: Discussionmentioning

confidence: 99%

Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Thus, tuberculosis is responsible for 2.5% of deaths in the world, which is the highest rate claimed by a single infectious agent. An M. tuberculosis knock-out mutant deficient in lipoprotein signal peptidase lspA showed reduced multiplication in bone marrow-derived macrophages, complete absence of lung pathology and a 1000-fold reduced number of colony forming units in a mouse model of infection (3,4). Likewise, lipoprotein synthesis contributes to virulence of other Grampositive pathogens, Listeria, Staphylococci, and Streptococci (5).…”

mentioning

confidence: 99%

Identification of Apolipoprotein N-Acyltransferase (Lnt) in Mycobacteria

Tschumi

Nai

Auchli³

et al. 2009

Journal of Biological Chemistry

Self Cite

110

View full text Add to dashboard Cite

show abstract

“…Bone marrow stem cells were isolated from mice femurs and differentiated for 7 days in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum (FCS), 10% L cell conditioned medium, and penicillin/streptomycin on petri dishes. The cells were then mounted on 0.7-mm glass coverslips in 24-well plates at 1.5 ϫ 10 5 to 2 ϫ 10 5 cells per well and infected with BCG as described previously (29). Colocalization studies were done as described previously (29), and the coverslip contents were left unidentified before analysis.…”

Section: Micementioning

confidence: 99%

“…The cells were then mounted on 0.7-mm glass coverslips in 24-well plates at 1.5 ϫ 10 5 to 2 ϫ 10 5 cells per well and infected with BCG as described previously (29). Colocalization studies were done as described previously (29), and the coverslip contents were left unidentified before analysis.…”

Section: Micementioning

confidence: 99%

Relief from Zmp1-Mediated Arrest of Phagosome Maturation Is Associated with Facilitated Presentation and Enhanced Immunogenicity of Mycobacterial Antigens

Johansen

Fettelschoss

Amstutz

et al. 2011

Clin. Vaccine Immunol.

Self Cite

View full text Add to dashboard Cite

Pathogenic mycobacteria escape host innate immune responses by blocking phagosome-lysosome fusion.Avoiding lysosomal delivery may also be involved in the capacity of mycobacteria to evade major histocompatibility complex (MHC) class I-or II-dependent T-cell responses. In this study, we used a genetic mutant of Mycobacterium bovis BCG that is unable to escape lysosomal transfer and show that presentation of mycobacterial antigens is affected by the site of intracellular residence. Compared to infection with wild-type BCG, infection of murine bone marrow-derived dendritic cells with a mycobacterial mutant deficient in zinc metalloprotease 1 (Zmp1) resulted in increased presentation of MHC class II-restricted antigens, as assessed by activation of mycobacterial Ag85A-specific T-cell hybridomas. The zmp1 deletion mutant was more immunogenic in vivo, as measured by delayed-type hypersensitivity (DTH), antigen-specific lymphocyte proliferation, and the frequency of antigen-specific gamma interferon (IFN-␥)-producing lymphocytes of both CD4 and CD8 subsets. In conclusion, our results suggest that phagosome maturation and lysosomal delivery of BCG facilitate mycobacterial antigen presentation and enhance immunogenicity.

show abstract

LspA inactivation in Mycobacterium tuberculosis results in attenuation without affecting phagosome maturation arrest

Cited by 28 publications

References 81 publications

Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

Identification of Apolipoprotein N-Acyltransferase (Lnt) in Mycobacteria

Relief from Zmp1-Mediated Arrest of Phagosome Maturation Is Associated with Facilitated Presentation and Enhanced Immunogenicity of Mycobacterial Antigens

Contact Info

Product

Resources

About