Staphylococcus aureus throat carriage is associated with ABO-/secretor status
Introduction
The global emergence of antibiotic resistant Staphylococcus aureus as a cause of morbidity in- and outside the health-care setting explains the focus of current research on the evolution and spread of such strains. Colonization of the human skin and mucosal surfaces very likely promotes this process through facilitating the exchange of resistance genes, exposure to antibacterial compounds, selection of resistant clones, and human to human transmission.
While marked progress has been made in clarifying risk factors and determinants of S. aureus nasal carriage1, 2, 3, 4 published research on factors that promote colonization of other body sites is scarce. This neglect seems well justified as it has been shown, that the nose is the primary site of colonization. From there, other body regions are colonized by manual spread and are thus likely to lose colonization after eradication of S. aureus from the nares.5, 6
Pharyngeal carriage of S. aureus, however, was recently shown to occur independently from colonization of the nares. In a large cross-sectional study of 1500 blood donors, 30% of those colonized were found to be exclusive throat and 27% exclusive nasal carriers while 43% were colonized at both sites.7 Furthermore, one longitudinal investigation found that about 40% of persistently colonized individuals carried S. aureus at most occasions in the throat only.8 These findings suggest that the host-factors involved in colonization of the nose and throat must be, at least partially, distinct.
The clinical and public health importance of throat carriage is supported by a variety of observations. In severely ill patients, colonization of the pharynx and upper respiratory tract has been found to be a risk factor for ventilator associated pneumonia9, 10 and eradication of such colonization to reduce this risk.11 Furthermore, it has been shown, that successful screening and eradication of methicillin resistant S. aureus colonization has to include separate sampling and antibacterial treatment of the throat.12, 13, 14 Finally, it is likely that throat carriage – as shown for nasal carriage15 – contributes towards the dissemination of bacteria into the environment through increased S. aureus dispersal during upper respiratory infections of viral origin.
It is generally agreed on that adhesion of microorganisms to epithelial surfaces is the first crucial step in establishing colonization.16 During this process, bacterial adhesins are thought to specifically recognize the epithelial surface.16 Carbohydrate residues of the glyococalix and glycoconjugates (i.e. glycoproteins and glycolipids) characterize the most outer parts of the epithelial lining and are thus likely to be of importance in establishing this first contact between host and pathogen.17, 18 The large diversity of such oligosaccharide chains together with evidence on their pathogen specificity gave rise to the hypothesis that their presence is a result of a co-evolutionary process balancing the relationship between potentially lethal pathogens and vertebrate hosts.17, 18
One group of glycans showing such striking diversity are histo-blood group antigens (HBGA). In particular those belonging to the ABH-/Lewis system have attracted significant interest as ligands for microorganisms. For instance, adhesion of Helicobacter pylori, Escherichia coli,19 Streptococcus pneumoniae,20 Salmonella typhimurium,21 and Norwalk virus22 to epithelial cells was found to be associated with the phenotypic expression of ABH and Lewis HBGAs.
The quantitative and qualitative presence of ABH-/Lewis HBGAs on epithelia and in body fluids is genetically determined and depends largely on a set of fucosyltransferases (FUT) that add monosaccharide units to precursor molecules in a stepwise manner.23 One key factor accounting for the variation in expression of these antigens is the α1,2 fucosyltransferase encoded by the FUT2-gene.23, 24 About 80% of Caucasian individuals carry a functional allele of the FUT2- or secretor gene (Se) while the remaining 20% do not.23 Individuals with the functional variant are generally referred to as secretors. Secretors express fucosylated ABH- and Lewis b (Leb) antigens in body fluids and on the surface of various tissues. By contrast, non-secretors are not able to synthesize H-antigen – the precursor of Leb and ABH-antigens – in cells where it is synthesized by the FUT2 enzyme, and are thus phenotypically characterized by the absence of ABH antigens and the presence of Lewis a (Lea) antigen in fluids and on several epithelial surfaces.23
Evidence, that the presence of HBGAs on epithelia and in body fluids (e.g. mucus) may also play a role in S. aureus colonization is limited and the few available studies are inconclusive and partially conflicting. One in vitro study showed enhanced binding of S. aureus to buccal epithelial cells of non-secretors compared to secretors and marked inhibition of this binding by pretreatment with anti-Lea antibodies.25 This binding of S. aureus to Lea was found to be associated with a 67 kDa adhesin on the S. aureus membrane.26 Although these observations support a specific binding of S. aureus to Lea, an earlier study failed to establish an association of secretor status with respiratory S. aureus colonization in patients with cystic fibrosis.27 Furthermore, one study in 326 health care workers observed a predominance of blood group A among persistent nasal S. aureus carriers but did not investigate for secretor status.28 Epidemiological studies trying to elucidate the presence of epistatic effects of the ABH and Lewis genes on the individual risk of being colonized with S. aureus are missing.
Such research could be of value in elucidating mechanisms that underlie the observed population variation in S. aureus colonization and their contribution towards individual patterns of colonization. The latter speculation is fostered by the description of substantial differences in AHB Lewis expression between different tissues and body regions.24 In the light of increasing interest in throat carriage as an additional reservoir for S. aureus,7, 8, 12, 29, 30, 31 we hypothesized that ABH/Lewis expression might influence an individual's propensity to be colonized with S. aureus in the nose and throat.
Section snippets
Study subjects and design
Within an on-going cohort on S. aureus colonization, we determined throat carriage of S. aureus in 227 healthy volunteers previously classified as non- or persistent nasal carriers of S. aureus. Throat carriage was identified by taking a single swab from the posterior pharyngeal wall. Non- and persistent nasal carriage status was defined as four negative or four positive microbiological results in sequential swabs from both anterior nares. Besides, we collected blood and saliva to determine the
Results
From a prospective cohort on nasal carriage of S. aureus we identified 227 individuals with established S. aureus nasal carrier status (156 persistent nasal carriers and 71 non-carriers) and determined the presence of S. aureus in the posterior mesopharynx. Demographic and anthropometric characteristics other than nasal carriage were similarly distributed between 77 pharyngeal carriers and 150 pharyngeal non-carriers of S. aureus (Table 1). Throat carriers were more likely to also be persistent
Discussion
This study provides evidence for an association of genetically determined HBGA expression with pharyngeal S. aureus colonization. Using non-secretors with blood group A as a comparator, non-secretors with blood group O had 6.5-times the odds of being colonized in the throat. By contrast, a similar comparison among secretors provided evidence for blood group O being protective. Among individuals with blood group A there was a trend for an inverse relationship after adjusting for differences in
Funding
No particular funding was received to support this work.
Conflicts of interests
All authors, no conflicts.
Acknowledgements
We would like to thank Martina Henk, Silvelia Grummes and Viola Galinat for her excellent technical assistance. We are also indebted to Heidrun Beer, Rita Ritter, Bernadette Vath and Sofia Theil for their support in recruiting study subjects.
References (38)
- et al.
The role of nasal carriage in Staphylococcus aureus infections
Lancet Infect Dis
(2005 Dec) - et al.
Screening for methicillin-resistant Staphylococcus aureus: which anatomical sites to culture?
J Hosp Infect
(2005 Dec) - et al.
Attachment of Staphylococcus aureus to eukaryotic cells and experimental pitfalls in staphylococcal adherence assays: a critical appraisal
J Microbiol Methods
(2002 Jan) - et al.
ABH and Lewis histo-blood group antigens, a model for the meaning of oligosaccharide diversity in the face of a changing world
Biochimie
(2001 Jul) - et al.
Isolation of an adhesin from Staphylococcus aureus that binds Lewis a blood group antigen and its relevance to sudden infant death syndrome
FEMS Immunol Med Microbiol
(1994 May) - et al.
The protective effect of breast feeding in relation to sudden infant death syndrome (SIDS): I. The effect of human milk and infant formula preparations on binding of toxigenic Staphylococcus aureus to epithelial cells
FEMS Immunol Med Microbiol
(1999 Aug 1) - et al.
Persistent nasal carriage of Staphylococcus aureus is associated with deficient induction of human beta-defensin 3 after sterile wounding of healthy skin in vivo
Infect Immun
(2011 Jul) - et al.
Are host genetics the predominant determinant of persistent nasal Staphylococcus aureus carriage in humans?
J Infect Dis
(2010 Sep 15) - et al.
Host polymorphisms in interleukin 4, complement factor H, and C-reactive protein associated with nasal carriage of Staphylococcus aureus and occurrence of boils
J Infect Dis
(2008 May 1) - et al.
Effect of mupirocin treatment on nasal, pharyngeal, and perineal carriage of Staphylococcus aureus in healthy adults
Antimicrob Agents Chemother
(2005 Apr)