Is Mannose‐Binding Lectin Deficiency Associated with Infection due to Gram‐Positive Bacteria?

Smithson, Àlex; Perelló, Rafael; Horcajada, Juan Pablo; Nicolás, J.M.; Lozano, Francisco

doi:10.1086/593106

Cited by 6 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In adults, high levels of WTA-specific antibodies interfere with MBL deposition on S. aureus. Additionally, mortality is not affected in MBL-deficient adults with S. aureus infections, suggesting a redundant role for MBL in the immune response against S. aureus in adults [59,60]. In contrast, detection of S. aureus by MBL is critical in infants since they lack high levels of WTA-specific antibodies as a result of a still developing adaptive immune system [22].…”

Section: Mblmentioning

confidence: 99%

Wall Teichoic Acid in Staphylococcus aureus Host Interaction

Dalen

Peschel

Sorge

2020

Trends in Microbiology

View full text Add to dashboard Cite

Staphylococcus aureus is a major opportunistic human pathogen that frequently causes disease in community and hospital settings. Nasal colonization is an important risk factor for developing invasive disease. Cell wall-associated glycopolymers called wall teichoic acids (WTAs) contribute to efficient nasal colonization by S. aureus. In addition, WTAs are key targets of the host immune system due to their accessibility and high abundance on the S. aureus cell surface. In this review we discuss the new insights into interactions between the host and S. aureus WTA and the implications of these interactions for preventative and therapeutic approaches against S. aureus-mediated disease.Teichoic Acids: At the Bacterium-Host Interface S. aureus is a Gram-positive opportunistic human pathogen that asymptomatically colonizes the nasopharynx of 20-30% of the human population. Nasal colonization is a risk factor for developing invasive infections, including pneumonia, osteomyelitis, endocarditis, and sepsis [1,2]. The teichoic acid (TA) glycopolymers (see Glossary) are major components of the Gram-positive bacterial cell wall, representing up to 60% of the total cell wall mass. TAs are either anchored in the plasma membrane as lipoteichoic acid (LTA), or covalently linked to peptidoglycan as wall teichoic acid (WTA). Both types of TA have crucial roles in cell growth, protection from environmental stress, and during colonization and infection of the host [3].TAs are key targets of the host immune system due to their exposure and high abundance on the S. aureus surface. In recent years, multiple molecular interactions between the human host and S. aureus TAs have been identified, of which the LTA-specific interactions are briefly summarized in Box 1. In this review we focus on the new insights into WTA-specific interactions of S. aureus with the human host. Importantly, we discuss the implications of these interactions for the development of preventative and therapeutic approaches against S. aureus. Structure of S. aureus WTAMany Gram-positive bacteria produce WTA, the structure of which can vary widely between species (Box 2). The majority of S. aureus lineages produce WTA that is comprised of up to 40 ribitolphosphate (RboP) subunits that are modified with D-alanine and N-acetylglucosamine (GlcNAc) residues (Figure 1A) [3], the biosynthesis of which is briefly summarized in Box 3. Importantly, the modifications of WTA functionalize the molecule, for instance by providing resistance to cationic antimicrobial peptides and antibiotics, mediating phage adsorption and facilitating colonization. Glycosylation of S. aureus RboP-WTAS. aureus RboP-WTA can be modified by three types of glycosylation, each requiring the activity of a dedicated glycosyltransferase that links a GlcNAc residue to the C3 or C4 RboP hydroxyl groups either in an αor β-configuration. This creates the following repertoire of GlcNAc modifications: α-1,4-GlcNAc catalyzed by TarM, β-1,4-GlcNAc catalyzed by TarS, and β-1,3-GlcNAc catalyzed by TarP (Figure 1A) [4...

show abstract

Section: Mblmentioning

confidence: 99%

Wall Teichoic Acid in Staphylococcus aureus Host Interaction

Dalen

Peschel

Sorge

2020

Trends in Microbiology

View full text Add to dashboard Cite

show abstract

“…This possibility has been proposed as a mechanism for some intracellular pathogens, such as tuberculosis and leishmaniasis, although the precise molecular mechanisms are not fully understood and further investigations are required [37], [38], [39]. These findings may explain why MBL deficiency has not been strongly associated with S. aureus infection in humans, particularly in adults, and the exact role of MBL in relation to MRSA associated virulence factors requires further investigation [12], [13], [14].…”

Section: Discussionmentioning

confidence: 99%

“…The innate immune system consists of innate immune cells, such as epithelial cells and phagocytes, and soluble factors such as complement proteins, coagulation factors and pattern recognition molecules, including mannose-binding lectin (MBL) [11]. Although genetic deficiency of MBL in mice increases infection susceptibility to certain pathogens, including S. aureus , this association is less apparent in humans, particularly in adults [12], [13], [14], [15].…”

Section: Introductionmentioning

confidence: 99%

Intradermal Immunization with Wall Teichoic Acid (WTA) Elicits and Augments an Anti-WTA IgG Response that Protects Mice from Methicillin-Resistant Staphylococcus aureus Infection Independent of Mannose-Binding Lectin Status

et al. 2013

View full text Add to dashboard Cite

The objectives of this study were to investigate the immune response to intradermal immunization with wall teichoic acid (WTA) and the effect of MBL deficiency in a murine model of infection with methicillin-resistant Staphylococcus aureus (MRSA). WTA is a bacterial cell wall component that is implicated in invasive infection. We tested susceptibility to MRSA infection in wild type (WT) and MBL deficient mice using two strains of MRSA: MW2, a community-associated MRSA (CA-MRSA); and COL, a healthcare-associated MRSA (HA-MRSA). We also performed in vitro assays to investigate the effects of anti-WTA IgG containing murine serum on complement activation and bacterial growth in whole blood. We found that MBL knockout (KO) mice are relatively resistant to a specific MRSA strain, MW2 CA-MRSA, compared to WT mice, while both strains of mice had similar susceptibility to a different strain, COL HA-MRSA. Intradermal immunization with WTA elicited and augmented an anti-WTA IgG response in both WT and MBL KO mice. WTA immunization significantly reduced susceptibility to both MW2 CA-MRSA and COL HA-MRSA, independent of the presence of MBL. The protective mechanisms of anti-WTA IgG are mediated at least in part by complement activation and clearance of bacteria from blood. The significance of these findings is that 1) Intradermal immunization with WTA induces production of anti-WTA IgG; and 2) This anti-WTA IgG response protects from infection with both MW2 CA-MRSA and COL HA-MRSA even in the absence of MBL, the deficiency of which is common in humans.

show abstract

“…aureus BSI. Previous studies which failed to demonstrate an effect of MBL deficiency [25,30] were likely underpowered as they had only examined a limited number of S. aureus BSI patients as part of larger sepsis trials, and controls were not matched.…”

Section: Discussionmentioning

confidence: 99%

Significance of Mannose-Binding Lectin Deficiency and Nucleotide-Binding Oligomerization Domain 2 Polymorphisms in Staphylococcus aureus Bloodstream Infections: A Case-Control Study

et al. 2013

View full text Add to dashboard Cite

BackgroundPathways coordinated by innate pattern recognition receptors like mannose-binding lectin (MBL) and nucleotide-binding oligomerization domain 2 (NOD2) are among the first immune responses to Staphylococcus aureus (S. aureus) bloodstream infections (BSI) in animal models, but human data are limited. Here, we investigated the role of MBL deficiency and NOD2 mutations in the predisposition to and severity of S. aureus BSI.Patients and MethodsA matched case-control study was undertaken involving 70 patients with S. aureus BSI and 70 age- and sex-matched hospitalized controls. MBL levels, MBL2 and NOD2 polymorphisms were analyzed.ResultsAfter adjusting for potential confounders, MBL deficiency (<0.5 µg/ml) was found less frequently in cases than controls (26 vs. 41%, OR 0.4, 95% confidence interval (CI) 0.20-0.95, p=0.04) as were low producing MBL genotypes (11 vs. 23%, OR 0.2, 95% CI 0.08-0.75, p=0.01), whereas NOD2 polymorphisms were similarly distributed. Cases with NOD2 polymorphisms had less organ dysfunction as shown by a lower SOFA score (median 2.5 vs. 4.5, p=0.02), whereas only severe MBL deficiency (<0.1 µg/ml) was associated with life-threatening S. aureus BSI (OR 5.6, 95% CI 1.25-24.85, p=0.02).ConclusionsContrary to animal model data, our study suggests MBL deficiency may confer protection against acquiring S. aureus BSI. NOD2 mutations were less frequently associated with multi-organ dysfunction. Further human studies of the innate immune response in S. aureus BSI are needed to identify suitable host targets in sepsis treatment.

show abstract

Is Mannose‐Binding Lectin Deficiency Associated with Infection due to Gram‐Positive Bacteria?

Cited by 6 publications

References 10 publications

Wall Teichoic Acid in Staphylococcus aureus Host Interaction

Wall Teichoic Acid in Staphylococcus aureus Host Interaction

Intradermal Immunization with Wall Teichoic Acid (WTA) Elicits and Augments an Anti-WTA IgG Response that Protects Mice from Methicillin-Resistant Staphylococcus aureus Infection Independent of Mannose-Binding Lectin Status

Significance of Mannose-Binding Lectin Deficiency and Nucleotide-Binding Oligomerization Domain 2 Polymorphisms in Staphylococcus aureus Bloodstream Infections: A Case-Control Study

Contact Info

Product

Resources

About