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The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota

Key Points

  • Many major bacterial pathogens can be found in the human microbiota and can infect sterile tissues if the host is immunocompromised. Exploring the ecology of such endogenous pathogens will help to develop new strategies for the prevention of opportunistic infections.

  • Staphylococcus aureus hides in the nasal microbiota of approximately 30% of the human population. The capacity of S. aureus to colonize seems to be controlled by the composition of the nasal microbiota.

  • The molecular mechanisms used by nasal commensals to outcompete S. aureus are probably multifactorial; some of them were recently elucidated and are discussed in this Review.

  • S. aureus competition with nasal commensals may be controlled by different capacities to adhere to limited epithelial attachment sites, to use limited nutrients, to release or resist antimicrobial molecules or to modulate epithelial inflammation.

  • Commensals with particularly potent ways of competing with S. aureus may be optimized and used in the future as nasal probiotics to reduce the risk of developing severe S. aureus infections.

Abstract

Although human colonization by facultative bacterial pathogens, such as Staphylococcus aureus, represents a major risk factor for invasive infections, the commensal lifestyle of such pathogens has remained a neglected area of research. S. aureus colonizes the nares of approximately 30% of the human population and recent studies suggest that the composition of highly variable nasal microbiota has a major role in promoting or inhibiting S. aureus colonization. Competition for epithelial attachment sites or limited nutrients, different susceptibilities to host defence molecules and the production of antimicrobial molecules may determine whether nasal bacteria outcompete each other. In this Review, we discuss recent insights into mechanisms that are used by S. aureus to prevail in the human nose and the counter-strategies that are used by other nasal bacteria to interfere with its colonization. Understanding such mechanisms will be crucial for the development of new strategies for the eradication of endogenous facultative pathogens.

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Figure 1: Mechanisms of competition between nasal bacteria.
Figure 2: Documented interference mechanisms of major nasal bacteria.
Figure 3: Epithelial ligands and bacterial adhesins in the anterior and posterior nasal cavity.
Figure 4: Antimicrobial molecules and mechanism used by nasal bacteria.

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Acknowledgements

Research in the author's laboratory was supported by grants from the Deutsche Forschungsgemeinschaft to C.W. (TRR34 and SFB766) and A.P. (TRR34, TRR156, SFB766, SFB685, GRK1708 and PE805/5-1), and from the Deutsches Zentrum für Infektionsforschung to C.W., B.K. and A.P. (TTU HAARBI).

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B.K., C.W., A.Z. and A.P. contributed equally to researching data for the article, providing a substantial contribution to discussions of the content and writing the article and to review and/or to edit the manuscript before submission.

Corresponding author

Correspondence to Andreas Peschel.

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Competing interests

The authors declare competing interest, as the University of Tübingen has filed a patent application on one of the antimicrobial substances mentioned in the Review (lugdunin).

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Glossary

Methicillin-resistant S. aureus

(MRSA). Staphylococcus aureus clones that are resistant to methicillin and most other β-lactam antibiotics following acquisition of the resistance gene mecA.

Decolonization

The eradication of one or several pathogenic species from the microbiota to prevent opportunistic infections.

Oropharynx

The part of the throat at the back of the mouth behind the oral cavity.

Community state types

(CSTs). The categorization or clustering of microbiome profiles according to their genetic composition.

Coagulase-negative Staphylococcus species

(CoNS). Includes all Staphylococcus species that do not express coagulase.

Anterior vestibule

Most anterior part of the nasal cavity lined by the differentiated epithelium of the skin.

Sphenoethmoidal recess

A small space in the nasal cavity into which the sphenoidal sinus opens.

Mucociliary clearance

Movement of the mucus that covers the respiratory epithelium toward the oropharynx caused by the beating of cilia.

Desquamated

The shedding of the outermost layer of a tissue, such as the skin.

Squamous cells

Layers of flat plate-like cells that make up most of the cells in the outer layer of the skin.

Mucins

A family of highly glycosylated proteins with high molecular weight that are produced in the epithelial tissues of most animals.

agr quorum sensing system

A quorum sensing system found in all Staphylococcus species. Agr consists of proteins that mediate the synthesis and secretion of an autoinducer peptide and a two-component regulatory system that responds to the peptide.

Sialic acids

N- or O-substituted derivatives of neuraminic acid, a monosaccharide that has a nine-carbon backbone. Sialic acids are widely distributed in the tissues of mammals and other multicellular organisms.

Non-ribosomal peptide synthetases

(NRPS). Protein complexes that can synthesize peptides and small proteins independently of mRNA and can also use non-proteinogenic amino acids, thereby increasing the variability of NRPS products.

Lanthionine bridges

Cyclic ring structures within peptides formed by the dehydration of serine or threonine residues followed by reaction of the resulting dehydro-amino acid with a cysteine to form thioether linkages.

Thiazole and oxazole heterocycles

Heterocyclic molecule components that contain both sulfur and nitrogen (thiazole), or oxygen and nitrogen (oxazole).

Pyridine rings

Nitrogen-containing aromatic hexamer components.

Macrolide

A natural product from the class of polyketides, which consist of a macrocyclic lactone ring with variable substituents.

Atopic dermatitis

A type of itchy skin inflammation that is frequently associated with Staphylococcus aureus skin colonization.

Peptidoglycan

A polymer that forms the bacterial cell wall that is composed of sugar chains interlinked by peptide chains.

Nasal instillation

A medical solution prepared for administration into the nose given in the form of nose drops, cream or nasal sprays.

Dysbiosis

Imbalance of the microbiota because of the over-representation or under-representation of particular bacterial species or strains, leading to diseases.

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Krismer, B., Weidenmaier, C., Zipperer, A. et al. The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota. Nat Rev Microbiol 15, 675–687 (2017). https://doi.org/10.1038/nrmicro.2017.104

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