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Murein lipoprotein is a critical outer membrane component involved in Salmonella enterica serovar typhimurium systemic infection.
Infect Immun. 2005 Feb; 73(2):1081-96.II

Abstract

Lipopolysaccharide (LPS) and Braun (murein) lipoprotein (Lpp) are major components of the outer membrane of gram-negative enteric bacteria that function as potent stimulators of inflammatory and immune responses. In a previous paper, we provided evidence that two functional copies of the lipoprotein gene (lppA and lppB) located on the chromosome of Salmonella enterica serovar Typhimurium contributed to bacterial virulence. In this study, we characterized lppA and lppB single-knockout (SKO) mutants and compared them with an lpp double-knockout (DKO) mutant using in vitro and in vivo models. Compared to the lpp DKO mutant, which was nonmotile, the motility of the lpp SKO mutants was significantly increased (73 to 77%), although the level of motility did not reach the level of wild-type (WT) S. enterica serovar Typhimurium. Likewise, the cytotoxicity was also significantly increased when T84 human intestinal epithelial cells and RAW264.7 murine macrophages were infected with the lpp SKO mutants compared to the cytotoxicity when cells were infected with the lpp DKO mutant. The level of interleukin-8 (IL-8) in polarized T84 cells infected with the lppB SKO mutant was significantly higher (two- to threefold higher), reaching the level in cells infected with WT S. enterica serovar Typhimurium, than the level in host cells infected with the lppA SKO mutant. The lpp DKO mutant induced minimal levels of IL-8. Similarly, sera from mice infected with the lppB SKO mutant contained 4.5- to 10-fold-higher levels of tumor necrosis factor-alpha and IL-6; the levels of these cytokines were 1.7- to 3.0-fold greater in the lppA SKO mutant-infected mice than in animals challenged with the lpp DKO mutant. The increased cytokine levels observed with the lppB SKO mutant in mice correlated with greater tissue damage in the livers and spleens of these mice than in the organs of animals infected with the lppA SKO and lpp DKO mutants. Moreover, the lppB SKO mutant-infected mice had increased susceptibility to death. Since the lpp DKO mutant retained intact LPS, we constructed an S. enterica serovar Typhimurium triple-knockout (TKO) mutant in which the lppA and lppB genes were deleted from an existing msbB mutant (msbB encodes an enzyme required for the acylation of lipid A). Compared to the lpp DKO and msbB SKO mutants, the lpp-msbB TKO mutant was unable to induce cytotoxicity and to produce cytokines and chemokines in vitro and in vivo. These studies provided the first evidence of the relative contributions of Lpp and lipid A acylation to Salmonella pathogenesis.

Authors+Show Affiliations

Department of Microbiology and Immunology, 301 University Blvd., University of Texas Medical Branch, Galveston, TX 77555-1070, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15664952

Citation

Fadl, A A., et al. "Murein Lipoprotein Is a Critical Outer Membrane Component Involved in Salmonella Enterica Serovar Typhimurium Systemic Infection." Infection and Immunity, vol. 73, no. 2, 2005, pp. 1081-96.
Fadl AA, Sha J, Klimpel GR, et al. Murein lipoprotein is a critical outer membrane component involved in Salmonella enterica serovar typhimurium systemic infection. Infect Immun. 2005;73(2):1081-96.
Fadl, A. A., Sha, J., Klimpel, G. R., Olano, J. P., Niesel, D. W., & Chopra, A. K. (2005). Murein lipoprotein is a critical outer membrane component involved in Salmonella enterica serovar typhimurium systemic infection. Infection and Immunity, 73(2), 1081-96.
Fadl AA, et al. Murein Lipoprotein Is a Critical Outer Membrane Component Involved in Salmonella Enterica Serovar Typhimurium Systemic Infection. Infect Immun. 2005;73(2):1081-96. PubMed PMID: 15664952.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Murein lipoprotein is a critical outer membrane component involved in Salmonella enterica serovar typhimurium systemic infection. AU - Fadl,A A, AU - Sha,J, AU - Klimpel,G R, AU - Olano,J P, AU - Niesel,D W, AU - Chopra,A K, PY - 2005/1/25/pubmed PY - 2005/3/12/medline PY - 2005/1/25/entrez SP - 1081 EP - 96 JF - Infection and immunity JO - Infect Immun VL - 73 IS - 2 N2 - Lipopolysaccharide (LPS) and Braun (murein) lipoprotein (Lpp) are major components of the outer membrane of gram-negative enteric bacteria that function as potent stimulators of inflammatory and immune responses. In a previous paper, we provided evidence that two functional copies of the lipoprotein gene (lppA and lppB) located on the chromosome of Salmonella enterica serovar Typhimurium contributed to bacterial virulence. In this study, we characterized lppA and lppB single-knockout (SKO) mutants and compared them with an lpp double-knockout (DKO) mutant using in vitro and in vivo models. Compared to the lpp DKO mutant, which was nonmotile, the motility of the lpp SKO mutants was significantly increased (73 to 77%), although the level of motility did not reach the level of wild-type (WT) S. enterica serovar Typhimurium. Likewise, the cytotoxicity was also significantly increased when T84 human intestinal epithelial cells and RAW264.7 murine macrophages were infected with the lpp SKO mutants compared to the cytotoxicity when cells were infected with the lpp DKO mutant. The level of interleukin-8 (IL-8) in polarized T84 cells infected with the lppB SKO mutant was significantly higher (two- to threefold higher), reaching the level in cells infected with WT S. enterica serovar Typhimurium, than the level in host cells infected with the lppA SKO mutant. The lpp DKO mutant induced minimal levels of IL-8. Similarly, sera from mice infected with the lppB SKO mutant contained 4.5- to 10-fold-higher levels of tumor necrosis factor-alpha and IL-6; the levels of these cytokines were 1.7- to 3.0-fold greater in the lppA SKO mutant-infected mice than in animals challenged with the lpp DKO mutant. The increased cytokine levels observed with the lppB SKO mutant in mice correlated with greater tissue damage in the livers and spleens of these mice than in the organs of animals infected with the lppA SKO and lpp DKO mutants. Moreover, the lppB SKO mutant-infected mice had increased susceptibility to death. Since the lpp DKO mutant retained intact LPS, we constructed an S. enterica serovar Typhimurium triple-knockout (TKO) mutant in which the lppA and lppB genes were deleted from an existing msbB mutant (msbB encodes an enzyme required for the acylation of lipid A). Compared to the lpp DKO and msbB SKO mutants, the lpp-msbB TKO mutant was unable to induce cytotoxicity and to produce cytokines and chemokines in vitro and in vivo. These studies provided the first evidence of the relative contributions of Lpp and lipid A acylation to Salmonella pathogenesis. SN - 0019-9567 UR - https://www.unboundmedicine.com/medline/citation/15664952/Murein_lipoprotein_is_a_critical_outer_membrane_component_involved_in_Salmonella_enterica_serovar_typhimurium_systemic_infection_ L2 - https://journals.asm.org/doi/10.1128/IAI.73.2.1081-1096.2005?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -