Spreading of a mycobacterial cell-surface lipid into host epithelial membranes promotes infectivity

Several virulence lipids populate the outer cell wall of pathogenic mycobacteria. Phthiocerol dimycocerosate (PDIM), one of the most abundant outer membrane lipids, plays important roles in both defending against host antimicrobial programs and in evading these programs altogether. Immediately following infection, mycobacteria rely on PDIM to evade Myd88-dependent recruitment of microbicidal monocytes which can clear infection. To circumvent the limitations in using genetics to understand virulence lipids, we developed a chemical approach to track PDIM during Mycobacterium marinum infection of zebrafish. We found that PDIM's methyl-branched lipid tails enabled it to spread into host epithelial membranes to prevent immune activation. Additionally, PDIM’s affinity for cholesterol promoted this phenotype; treatment of zebrafish with statins, cholesterol synthesis inhibitors, decreased spreading and provided protection from infection. This work establishes that interactions between host and pathogen lipids influence mycobacterial infectivity and suggests the use of statins as tuberculosis preventive therapy by inhibiting PDIM spread.

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Spreading of a mycobacterial cell surface lipid into host epithelial membranes promotes infectivity

10.1101/845081 ◽

2019 ◽

Cited By ~ 5

Author(s):

C.J. Cambier ◽

Steven M. Banik ◽

Joseph A. Buonomo ◽

Carolyn R. Bertozzi

Keyword(s):

Cell Wall ◽

Cell Surface ◽

Cholesterol Synthesis ◽

Membrane Lipids ◽

Preventive Therapy ◽

Outer Cell ◽

Surface Lipid ◽

Toll Like Receptor ◽

Epithelial Membranes ◽

Outer Cell Wall

ABSTRACTSeveral virulence lipids populate the outer cell wall of pathogenic mycobacteria (Jackson, 2014). Phthiocerol dimycocerosate (PDIM), one of the most abundant outer membrane lipids (Anderson, 1929), plays important roles in both defending against host antimicrobial programs (Camacho et al., 2001; Cox et al., 1999; Murry et al., 2009) and in evading these programs altogether (Cambier et al., 2014a; Rousseau et al., 2004). Immediately following infection, mycobacteria rely on PDIM to evade toll-like receptor (TLR)-dependent recruitment of bactericidal monocytes which can clear infection (Cambier et al., 2014b). To circumvent the limitations in using genetics to understand virulence lipid function, we developed a chemical approach to introduce a clickable, semi-synthetic PDIM onto the cell wall of Mycobacterium marinum. Upon infection of zebrafish, we found that PDIM rapidly spreads into host epithelial membranes, and that this spreading inhibits TLR activation. PDIM’s ability to spread into epithelial membranes correlated with its enhanced fluidity afforded by its methyl-branched mycocerosic acids. Additionally, PDIM’s affinity for cholesterol promoted its occupation of epithelial membranes; treatment of zebrafish with statins, cholesterol synthesis inhibitors, decreased spreading and provided protection from infection. This work establishes that interactions between host and pathogen lipids influence mycobacterial infectivity and suggests the use of statins as tuberculosis preventive therapy by inhibiting PDIM spread.

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The ultrastructure of the outer cell wall-layer ofChlorella mutants with and without sporopollenin

Plant Systematics and Evolution ◽

10.1007/bf00984613 ◽

1981 ◽

Vol 138 (1-2) ◽

pp. 121-137 ◽

Cited By ~ 24

Author(s):

J. Burczyk ◽

M. Hesse

Keyword(s):

Cell Wall ◽

Wall Layer ◽

Outer Cell ◽

Cell Wall Layer ◽

Outer Cell Wall

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A freeze-etch study of plant cell walls for ectodesmata

Canadian Journal of Botany ◽

10.1139/b74-260 ◽

1974 ◽

Vol 52 (9) ◽

pp. 2033-2036 ◽

Cited By ~ 7

Author(s):

N. C. Lyon ◽

W. C. Mueller

Keyword(s):

Cell Wall ◽

Cell Walls ◽

Leaf Tissue ◽

Physicochemical Characteristics ◽

Outer Cell ◽

Plantago Major ◽

Plant Cell Walls ◽

Phaseolus Vulgaris L ◽

Epidermal Cell Wall ◽

Outer Cell Wall

Leaf tissue of Phaseolus vulgaris L. and Plantago major L. was prepared by the freeze-etch technique and examined in the electron microscope for the presence of ectodesmata. No structures analagous to ectodesmata observed with light microscopy could be found in freeze-etched preparations of chemically unfixed material or in material fixed only in glutaraldehyde. Objects appearing as broad, shallow, granular areas in the epidermal cell wall beneath the cuticle were observed in leaf replicas after fixation in complete sublimate fixative, the acid components of the sublimate fixative, or mercuric chloride alone. Because of their distribution and location, these objects can be considered analagous to ectodesmata observed by light microscopists. Because these areas occur only in chemically fixed walls and are localized within the walls in discrete areas, their presence supports the contention that ectodesmata are sites in the outer cell wall with defined physicochemical characteristics.

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Changes in structure of red pepper (Capsicum annuum L.) seedlings shoots under aluminum stress conditions

Acta Agrobotanica ◽

10.5586/aa.2007.010 ◽

2012 ◽

Vol 60 (1) ◽

pp. 85-93 ◽

Cited By ~ 2

Author(s):

Agata Konarska

Keyword(s):

Cell Wall ◽

Capsicum Annuum ◽

Red Pepper ◽

Outer Cell ◽

Aluminum Stress ◽

Water Culture ◽

Anatomical Features ◽

Parenchyma Cells ◽

Al Treatment ◽

Outer Cell Wall

The seedlings of the red pepper (Capsicum annuum L.) cv. Trapez grown in water culture for a period of 14 days with Al (0, 10, 20 and 40 mg·dm-3 AlCl3·6 H2O). Some morphological and anatomical features of red pepper shoots were analyzed. Reduction in height and diameter of stems as well as decrease in fresh mass of shoots were observed after Al-treatment. In the hypocotyl the thickness of cortex parenchyma layer and the size of their cells were reduced. The aluminum treatment resulted in the increased in thickness of the epidermis outer cell wall. Under Al stress in the cotrex and the central cylinder parenchyma cells were present numerous enlarge plastids which contained large grains of starch and dark little bodies which were possible aluminum deposits. They weren`t observed in control seedlings.

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Silver nanoparticles (AgNPs) internalization and passage through the Lactuca sativa (Asteraceae) outer cell wall

Functional Plant Biology ◽

10.1071/fp21161 ◽

2021 ◽

Author(s):

Sergimar Kennedy de Paiva Pinheiro ◽

Thaiz Batista Azevedo Rangel Miguel ◽

Marlos de Medeiros Chaves ◽

Francisco Claudio de Freitas Barros ◽

Camila Pessoa Farias ◽

...

Keyword(s):

Silver Nanoparticles ◽

Cell Wall ◽

Lactuca Sativa ◽

Outer Cell ◽

Outer Cell Wall

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Production of Monoclonal Antibodies Against the Outer Cell Wall ofClostridium tyrobutyricum

Hybridoma ◽

10.1089/hyb.1994.13.45 ◽

1994 ◽

Vol 13 (1) ◽

pp. 45-51 ◽

Cited By ~ 10

Author(s):

FRANCOISE TALBOT ◽

GEORGES ROBREAU ◽

FRANCOISE GUEGUEN ◽

ROGER MALCOSTE

Keyword(s):

Cell Wall ◽

Monoclonal Antibodies ◽

Outer Cell ◽

Outer Cell Wall

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Conidial Hydrophobins of Aspergillus fumigatus

Applied and Environmental Microbiology ◽

10.1128/aem.69.3.1581-1588.2003 ◽

2003 ◽

Vol 69 (3) ◽

pp. 1581-1588 ◽

Cited By ~ 150

Author(s):

Sophie Paris ◽

Jean-Paul Debeaupuis ◽

Reto Crameri ◽

Marilyn Carey ◽

Franck Charlès ◽

...

Keyword(s):

Cell Wall ◽

Aspergillus Fumigatus ◽

Amorphous Layer ◽

Wall Layer ◽

Host Cells ◽

Outer Cell ◽

Host Immune System ◽

Wild Type ◽

Cell Wall Layer ◽

Outer Cell Wall

ABSTRACT The surface of Aspergillus fumigatus conidia, the first structure recognized by the host immune system, is covered by rodlets. We report that this outer cell wall layer contains two hydrophobins, RodAp and RodBp, which are found as highly insoluble complexes. The RODA gene was previously characterized, and ΔrodA conidia do not display a rodlet layer (N. Thau, M. Monod, B. Crestani, C. Rolland, G. Tronchin, J. P. Latgé, and S. Paris, Infect. Immun. 62:4380-4388, 1994). The RODB gene was cloned and disrupted. RodBp was highly homologous to RodAp and different from DewAp of A. nidulans. ΔrodB conidia had a rodlet layer similar to that of the wild-type conidia. Therefore, unlike RodAp, RodBp is not required for rodlet formation. The surface of ΔrodA conidia is granular; in contrast, an amorphous layer is present at the surface of the conidia of the ΔrodA ΔrodB double mutant. These data show that RodBp plays a role in the structure of the conidial cell wall. Moreover, rodletless mutants are more sensitive to killing by alveolar macrophages, suggesting that RodAp or the rodlet structure is involved in the resistance to host cells.

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