Limits...
A nasal epithelial receptor for Staphylococcus aureus WTA governs adhesion to epithelial cells and modulates nasal colonization.

Baur S, Rautenberg M, Faulstich M, Faulstich M, Grau T, Severin Y, Unger C, Hoffmann WH, Rudel T, Autenrieth IB, Weidenmaier C - PLoS Pathog. (2014)

Bottom Line: The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity.When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization.More importantly, colonization stayed low over an extended period of 6 days.

View Article: PubMed Central - PubMed

Affiliation: Interfacultary Institute for Microbiology and Infection Medicine Tübingen, Department of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany.

ABSTRACT
Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization.

Show MeSH

Related in: MedlinePlus

SREC-I on nasal epithelila cells.Surface exposure of SREC-I on HNECs and CRNECs was monitored by FACS with the same anti-human SREC-I antibody and isotype control. Statistical evaluation on HNECs (A) and on CRNECs (B). Data represent means ± SD of 3 or 4 independent experiments. Statistical analysis was performed by Student's t-test. Significant differences are indicated by one (P<0.05), two (P<0.01), or three (P<0.001) asterisks (*).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4006915&req=5

ppat-1004089-g001: SREC-I on nasal epithelila cells.Surface exposure of SREC-I on HNECs and CRNECs was monitored by FACS with the same anti-human SREC-I antibody and isotype control. Statistical evaluation on HNECs (A) and on CRNECs (B). Data represent means ± SD of 3 or 4 independent experiments. Statistical analysis was performed by Student's t-test. Significant differences are indicated by one (P<0.05), two (P<0.01), or three (P<0.001) asterisks (*).

Mentions: For detection of SREC-I by FACS analysis we used an anti-human SREC-I antibody and appropriate isotype controls. Both HNECs and CRNECs stained positive for the receptor with this antibody (Figure S2B and Figure 1). RT-PCR Primers were designed based on the mouse and human genome sequence for SREC-I. For both cell types SREC-I mRNA expression could be detected (Figure S2C). Confocal microscopy, employing the same primary antibodies used in the FACS analysis, revealed a weak but specific signal for SREC-I on HNECs and CRNECs (Figure S3). We therefore conclude that SREC-I shows considerable surface exposition on both CRNECs and HNECs.


A nasal epithelial receptor for Staphylococcus aureus WTA governs adhesion to epithelial cells and modulates nasal colonization.

Baur S, Rautenberg M, Faulstich M, Faulstich M, Grau T, Severin Y, Unger C, Hoffmann WH, Rudel T, Autenrieth IB, Weidenmaier C - PLoS Pathog. (2014)

SREC-I on nasal epithelila cells.Surface exposure of SREC-I on HNECs and CRNECs was monitored by FACS with the same anti-human SREC-I antibody and isotype control. Statistical evaluation on HNECs (A) and on CRNECs (B). Data represent means ± SD of 3 or 4 independent experiments. Statistical analysis was performed by Student's t-test. Significant differences are indicated by one (P<0.05), two (P<0.01), or three (P<0.001) asterisks (*).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4006915&req=5

ppat-1004089-g001: SREC-I on nasal epithelila cells.Surface exposure of SREC-I on HNECs and CRNECs was monitored by FACS with the same anti-human SREC-I antibody and isotype control. Statistical evaluation on HNECs (A) and on CRNECs (B). Data represent means ± SD of 3 or 4 independent experiments. Statistical analysis was performed by Student's t-test. Significant differences are indicated by one (P<0.05), two (P<0.01), or three (P<0.001) asterisks (*).
Mentions: For detection of SREC-I by FACS analysis we used an anti-human SREC-I antibody and appropriate isotype controls. Both HNECs and CRNECs stained positive for the receptor with this antibody (Figure S2B and Figure 1). RT-PCR Primers were designed based on the mouse and human genome sequence for SREC-I. For both cell types SREC-I mRNA expression could be detected (Figure S2C). Confocal microscopy, employing the same primary antibodies used in the FACS analysis, revealed a weak but specific signal for SREC-I on HNECs and CRNECs (Figure S3). We therefore conclude that SREC-I shows considerable surface exposition on both CRNECs and HNECs.

Bottom Line: The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity.When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization.More importantly, colonization stayed low over an extended period of 6 days.

View Article: PubMed Central - PubMed

Affiliation: Interfacultary Institute for Microbiology and Infection Medicine Tübingen, Department of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany.

ABSTRACT
Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization.

Show MeSH
Related in: MedlinePlus