Staphylococcus aureus Colonization of the Mouse Gastrointestinal Tract Is Modulated by Wall Teichoic Acid, Capsule, and Surface Proteins
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Staphylococcus aureus Colonization of the Mouse Gastrointestinal Tract Is Modulated by Wall Teichoic Acid, Capsule, and Surface Proteins. / Misawa, Yoshiki; Kelley, Kathryn A; Wang, Xiaogang; Wang, Linhui; Park, Wan Beom; Birtel, Johannes; Saslowsky, David; Lee, Jean C.
In: PLOS PATHOG, Vol. 11, No. 7, 07.2015, p. e1005061.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Staphylococcus aureus Colonization of the Mouse Gastrointestinal Tract Is Modulated by Wall Teichoic Acid, Capsule, and Surface Proteins
AU - Misawa, Yoshiki
AU - Kelley, Kathryn A
AU - Wang, Xiaogang
AU - Wang, Linhui
AU - Park, Wan Beom
AU - Birtel, Johannes
AU - Saslowsky, David
AU - Lee, Jean C
PY - 2015/7
Y1 - 2015/7
N2 - Staphylococcus aureus colonizes the nose, throat, skin, and gastrointestinal (GI) tract of humans. GI carriage of S. aureus is difficult to eradicate and has been shown to facilitate the transmission of the bacterium among individuals. Although staphylococcal colonization of the GI tract is asymptomatic, it increases the likelihood of infection, particularly skin and soft tissue infections caused by USA300 isolates. We established a mouse model of persistent S. aureus GI colonization and characterized the impact of selected surface antigens on colonization. In competition experiments, an acapsular mutant colonized better than the parental strain Newman, whereas mutants defective in sortase A and clumping factor A showed impaired ability to colonize the GI tract. Mutants lacking protein A, clumping factor B, poly-N-acetyl glucosamine, or SdrCDE showed no defect in colonization. An S. aureus wall teichoic acid (WTA) mutant (ΔtagO) failed to colonize the mouse nose or GI tract, and the tagO and clfA mutants showed reduced adherence in vitro to intestinal epithelial cells. The tagO mutant was recovered in lower numbers than the wild type strain in the murine stomach and duodenum 1 h after inoculation. This reduced fitness correlated with the in vitro susceptibility of the tagO mutant to bile salts, proteases, and a gut-associated defensin. Newman ΔtagO showed enhanced susceptibility to autolysis, and an autolysin (atl) tagO double mutant abrogated this phenotype. However, the atl tagO mutant did not survive better in the mouse GI tract than the tagO mutant. Our results indicate that the failure of the tagO mutant to colonize the GI tract correlates with its poor adherence and susceptibility to bactericidal factors within the mouse gut, but not to enhanced activity of its major autolysin.
AB - Staphylococcus aureus colonizes the nose, throat, skin, and gastrointestinal (GI) tract of humans. GI carriage of S. aureus is difficult to eradicate and has been shown to facilitate the transmission of the bacterium among individuals. Although staphylococcal colonization of the GI tract is asymptomatic, it increases the likelihood of infection, particularly skin and soft tissue infections caused by USA300 isolates. We established a mouse model of persistent S. aureus GI colonization and characterized the impact of selected surface antigens on colonization. In competition experiments, an acapsular mutant colonized better than the parental strain Newman, whereas mutants defective in sortase A and clumping factor A showed impaired ability to colonize the GI tract. Mutants lacking protein A, clumping factor B, poly-N-acetyl glucosamine, or SdrCDE showed no defect in colonization. An S. aureus wall teichoic acid (WTA) mutant (ΔtagO) failed to colonize the mouse nose or GI tract, and the tagO and clfA mutants showed reduced adherence in vitro to intestinal epithelial cells. The tagO mutant was recovered in lower numbers than the wild type strain in the murine stomach and duodenum 1 h after inoculation. This reduced fitness correlated with the in vitro susceptibility of the tagO mutant to bile salts, proteases, and a gut-associated defensin. Newman ΔtagO showed enhanced susceptibility to autolysis, and an autolysin (atl) tagO double mutant abrogated this phenotype. However, the atl tagO mutant did not survive better in the mouse GI tract than the tagO mutant. Our results indicate that the failure of the tagO mutant to colonize the GI tract correlates with its poor adherence and susceptibility to bactericidal factors within the mouse gut, but not to enhanced activity of its major autolysin.
KW - Animals
KW - Anti-Bacterial Agents/metabolism
KW - Bacterial Adhesion/drug effects
KW - Bacterial Capsules/metabolism
KW - Cell Wall/metabolism
KW - Gastrointestinal Diseases/metabolism
KW - Humans
KW - Membrane Proteins/metabolism
KW - Mice
KW - N-Acetylmuramoyl-L-alanine Amidase/metabolism
KW - Staphylococcal Infections/microbiology
KW - Staphylococcus aureus/drug effects
KW - Teichoic Acids/metabolism
U2 - 10.1371/journal.ppat.1005061
DO - 10.1371/journal.ppat.1005061
M3 - SCORING: Journal article
C2 - 26201029
VL - 11
SP - e1005061
JO - PLOS PATHOG
JF - PLOS PATHOG
SN - 1553-7366
IS - 7
ER -