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.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Tacconelli, E., Autenrieth, I. B. & Peschel, A. Fighting the enemy within. Science 355, 689–690 (2017).
Weidenmaier, C., Goerke, C. & Wolz, C. Staphylococcus aureus determinants for nasal colonization. Trends Microbiol. 20, 243–250 (2012).
Brugger, S. D., Bomar, L. & Lemon, K. P. Commensal–pathogen interactions along the human nasal passages. PLoS Pathog. 12, e1005633 (2016).
Mulcahy, M. E. & McLoughlin, R. M. Host–bacterial crosstalk determines Staphylococcus aureus nasal colonization. Trends Microbiol. 24, 872–886 (2016).
Bode, L. G. et al. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N. Engl. J. Med. 362, 9–17 (2010).
von Eiff, C., Becker, K., Machka, K., Stammer, H. & Peters, G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N. Engl. J. Med. 344, 11–16 (2001). This study shows that nasal S. aureus carriage is the major reservoir for S. aureus infections.
Septimus, E. J. & Schweizer, M. L. Decolonization in prevention of health care-associated infections. Clin. Microbiol. Rev. 29, 201–222 (2016).
Poovelikunnel, T., Gethin, G. & Humphreys, H. Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA. J. Antimicrob. Chemother. 70, 2681–2692 (2015).
Antonov, N. K. et al. High prevalence of mupirocin resistance in Staphylococcus aureus isolates from a pediatric population. Antimicrob. Agents Chemother. 59, 3350–3356 (2015).
Fischbach, M. A. & Segre, J. A. Signaling in host-associated microbial communities. Cell 164, 1288–1300 (2016).
Liu, C. M. et al. Staphylococcus aureus and the ecology of the nasal microbiome. Sci. Adv. 1, e1400216 (2015). This study describes the nasal microbiome composition of 89 humans at the species level and defines community sequence types.
Wos-Oxley, M. L. et al. A poke into the diversity and associations within human anterior nare microbial communities. ISME J. 4, 839–851 (2010).
Kluytmans, J., van Belkum, A. & Verbrugh, H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin. Microbiol. Rev. 10, 505–520 (1997).
Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).
Frank, D. N. et al. The human nasal microbiota and Staphylococcus aureus carriage. PLoS ONE 5, e10598 (2010).
Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).
Yan, M. et al. Nasal microenvironments and interspecific interactions influence nasal microbiota complexity and S. aureus carriage. Cell Host Microbe 14, 631–640 (2013).
Grice, E. A. et al. Topographical and temporal diversity of the human skin microbiome. Science 324, 1190–1192 (2009).
Ravel, J. et al. Vaginal microbiome of reproductive-age women. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4680–4687 (2011).
Segata, N. et al. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 13, R42 (2012).
Bokulich, N. A. et al. Quality-filtering vastly improves diversity estimates from Illumina amplicon sequencing. Nat. Methods 10, 57–59 (2013).
Warnecke, F. et al. Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite. Nature 450, 560–565 (2007).
Kaspar, U. et al. The culturome of the human nose habitats reveals individual bacterial fingerprint patterns. Environ. Microbiol. 18, 2130–2142 (2016). This study discusses how nasal microbiomes and culturomes differ, and shows that many bacteria from the culturome are not identified by typical microbiome analyses.
Misic, A. M. et al. The shared microbiota of humans and companion animals as evaluated from Staphylococcus carriage sites. Microbiome 3, 2 (2015).
Weese, J. S., Slifierz, M., Jalali, M. & Friendship, R. Evaluation of the nasal microbiota in slaughter-age pigs and the impact on nasal methicillin-resistant Staphylococcus aureus (MRSA) carriage. BMC Vet. Res. 10, 69 (2014).
Chaves-Moreno, D. et al. The microbial community structure of the cotton rat nose. Environ. Microbiol. Rep. 7, 929–935 (2015).
Bal, A. M. et al. Genomic insights into the emergence and spread of international clones of healthcare-, community- and livestock-associated meticillin-resistant Staphylococcus aureus: blurring of the traditional definitions. J. Glob. Antimicrob. Resist. 6, 95–101 (2016).
Peterson, S. W. et al. A study of the infant nasal microbiome development over the first year of life and in relation to their primary adult caregivers using cpn60 universal target (UT) as a phylogenetic marker. PLoS ONE 11, e0152493 (2016).
Man, W. H., de Steenhuijsen Piters, W. A. & Bogaert, D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat. Rev. Microbiol. 15, 259–270 (2017).
Biesbroek, G. et al. Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am. J. Respir. Crit. Care Med. 190, 1283–1292 (2014).
Faust, K. et al. Microbial co-occurrence relationships in the human microbiome. PLoS Comput. Biol. 8, e1002606 (2012).
Lemon, K. P. et al. Comparative analyses of the bacterial microbiota of the human nostril and oropharynx. mBio 1, e00129-10 (2010).
Becker, K., Heilmann, C. & Peters, G. Coagulase-negative staphylococci. Clin. Microbiol. Rev. 27, 870–926 (2014).
Camarinha-Silva, A., Jauregui, R., Pieper, D. H. & Wos-Oxley, M. L. The temporal dynamics of bacterial communities across human anterior nares. Environ. Microbiol. Rep. 4, 126–132 (2012).
Olsen, K. et al. Staphylococcus aureus nasal carriage is associated with serum 25-hydroxyvitamin D levels, gender and smoking status. The Tromso Staph and Skin Study. Eur. J. Clin. Microbiol. Infect. Dis. 31, 465–473 (2012).
Shukla, S. K., Rose, W. & Schrodi, S. J. Complex host genetic susceptibility to Staphylococcus aureus infections. Trends Microbiol. 23, 529–536 (2015).
Andersen, P. S. et al. Influence of host genetics and environment on nasal carriage of Staphylococcus aureus in Danish middle-aged and elderly twins. J. Infect. Dis. 206, 1178–1184 (2012).
Camarinha-Silva, A. et al. Comparing the anterior nare bacterial community of two discrete human populations using Illumina amplicon sequencing. Environ. Microbiol. 16, 2939–2952 (2014).
Mirzaei, M. K. & Maurice, C. F. Menage a trois in the human gut: interactions between host, bacteria and phages. Nat. Rev. Microbiol. 15, 397–408 (2017).
Oh, J. et al. Biogeography and individuality shape function in the human skin metagenome. Nature 514, 59–64 (2014).
McCarthy, A. J. et al. Extensive horizontal gene transfer during Staphylococcus aureus co-colonization in vivo. Genome Biol. Evol. 6, 2697–2708 (2014). This study reveals how phage-mediated horizontal gene transfer in the nose controls S. aureus evolution.
Winstel, V. et al. Wall teichoic acid structure governs horizontal gene transfer between major bacterial pathogens. Nat. Commun. 4, 2345 (2013).
Schade, J. & Weidenmaier, C. Cell wall glycopolymers of Firmicutes and their role as nonprotein adhesins. FEBS Lett. 590, 3758–3771 (2016).
Geoghegan, J. A. & Foster, T. J. Cell wall-anchored surface proteins of Staphylococcus aureus: many proteins, multiple functions. Curr. Top. Microbiol. Immunol. http://dx.doi.org/10.1007/82_2015_5002 (2015).
Corrigan, R. M., Miajlovic, H. & Foster, T. J. Surface proteins that promote adherence of Staphylococcus aureus to human desquamated nasal epithelial cells. BMC Microbiol. 9, 22 (2009).
Baur, S. et al. A nasal epithelial receptor for Staphylococcus aureus WTA governs adhesion to epithelial cells and modulates nasal colonization. PLoS Pathog. 10, e1004089 (2014). This article provides the first evidence for a role of the scavenger receptor SREC1 in WTA-mediated binding of S. aureus to nasal epithelial cells and nasal colonization.
Weidenmaier, C. et al. Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections. Nat. Med. 10, 243–245 (2004).
Mulcahy, M. E. et al. Nasal colonisation by Staphylococcus aureus depends upon clumping factor B binding to the squamous epithelial cell envelope protein loricrin. PLoS Pathog. 8, e1003092 (2012). This study identifies loricrin as the ClfB ligand on squamous nasal epithelial cells, with a crucial role in S. aureus nasal colonization.
Krismer, B. & Peschel, A. Does Staphylococcus aureus nasal colonization involve biofilm formation? Future Microbiol. 6, 489–493 (2011).
Wollenberg, M. S. et al. Propionibacterium-produced coproporphyrin III induces Staphylococcus aureus aggregation and biofilm formation. mBio 5, e01286-14 (2014).
Burian, M. et al. Temporal expression of adhesion factors and activity of global regulators during establishment of Staphylococcus aureus nasal colonization. J. Infect. Dis. 201, 1414–1421 (2010).
Foster, T. J., Geoghegan, J. A., Ganesh, V. K. & Hook, M. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat. Rev. Microbiol. 12, 49–62 (2014).
Weidenmaier, C. & Peschel, A. Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions. Nat. Rev. Microbiol. 6, 276–287 (2008).
Neuhaus, F. C. & Baddiley, J. A continuum of anionic charge: structures and functions of d-alanyl-teichoic acids in Gram-positive bacteria. Microbiol. Mol. Biol. Rev. 67, 686–723 (2003). This is a comprehensive review on charged cell wall glycopolymers such as teichoic acids.
Winstel, V. et al. Wall teichoic acid glycosylation governs Staphylococcus aureus nasal colonization. mBio 6, e00632-15 (2015).
Weidenmaier, C. & Lee, J. C. Structure and function of surface polysaccharides of Staphylococcus aureus. Curr. Top. Microbiol. Immunol. http://dx.doi.org/10.1007/82_2015_5018 (2016).
Cole, A. M. et al. Determinants of Staphylococcus aureus nasal carriage. Clin. Diagn. Lab Immunol. 8, 1064–1069 (2001). This article describes antimicrobial proteins in human nasal fluid.
Ten Broeke-Smits, N. J., Kummer, J. A., Bleys, R. L., Fluit, A. C. & Boel, C. H. Hair follicles as a niche of Staphylococcus aureus in the nose; is a more effective decolonisation strategy needed? J. Hosp. Infect. 76, 211–214 (2010).
O'Brien, L. M., Walsh, E. J., Massey, R. C., Peacock, S. J. & Foster, T. J. Staphylococcus aureus clumping factor B (ClfB) promotes adherence to human type I cytokeratin 10: implications for nasal colonization. Cell. Microbiol. 4, 759–770 (2002).
Clarke, S. R. et al. Iron-regulated surface determinant protein A mediates adhesion of Staphylococcus aureus to human corneocyte envelope proteins. Infect. Immun. 77, 2408–2416 (2009).
Askarian, F. et al. The interaction between Staphylococcus aureus SdrD and desmoglein 1 is important for adhesion to host cells. Sci. Rep. 6, 22134 (2016).
Shuter, J., Hatcher, V. B. & Lowy, F. D. Staphylococcus aureus binding to human nasal mucin. Infect. Immun. 64, 310–318 (1996).
Le, K. Y. & Otto, M. Quorum-sensing regulation in staphylococci — an overview. Front. Microbiol. 6, 1174 (2015).
Pynnonen, M., Stephenson, R. E., Schwartz, K., Hernandez, M. & Boles, B. R. Hemoglobin promotes Staphylococcus aureus nasal colonization. PLoS Pathog. 7, e1002104 (2011).
Ramsey, M. M., Freire, M. O., Gabrilska, R. A., Rumbaugh, K. P. & Lemon, K. P. Staphylococcus aureus shifts toward commensalism in response to Corynebacterium species. Front. Microbiol. 7, 1230 (2016). This study reports that a nasal commensal inhibits S. aureus quorum sensing.
Iwase, T. et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465, 346–349 (2010). This article describes that S. epidermidis strains that produce the protease Esp inhibit S. aureus nasal colonization.
Sugimoto, S. et al. Staphylococcus epidermidis Esp degrades specific proteins associated with Staphylococcus aureus biofilm formation and host–pathogen interaction. J. Bacteriol. 195, 1645–1655 (2013).
Roche, F. M., Meehan, M. & Foster, T. J. The Staphylococcus aureus surface protein SasG and its homologues promote bacterial adherence to human desquamated nasal epithelial cells. Microbiology 149, 2759–2767 (2003).
Zapotoczna, M., Heilbronner, S., Speziale, P. & Foster, T. J. Iron-regulated surface determinant (Isd) proteins of Staphylococcus lugdunensis. J. Bacteriol. 194, 6453–6467 (2012).
Krismer, B. et al. Nutrient limitation governs Staphylococcus aureus metabolism and niche adaptation in the human nose. PLoS Pathog. 10, e1003862 (2014). This study reveals how poor nutrient supply is in the nose.
Vanthanouvong, V. & Roomans, G. M. Methods for determining the composition of nasal fluid by X-ray microanalysis. Microsc. Res. Tech. 63, 122–128 (2004).
Chaves-Moreno, D. et al. Exploring the transcriptome of Staphylococcus aureus in its natural niche. Sci. Rep. 6, 33174 (2016).
Ahluwalia, A. et al. Nasal colonization with Staphylococcus aureus in patients with diabetes mellitus. Diabet Med. 17, 487–488 (2000).
Olson, M. E., King, J. M., Yahr, T. L. & Horswill, A. R. Sialic acid catabolism in Staphylococcus aureus. J. Bacteriol. 195, 1779–1788 (2013).
Bruggemann, H. et al. The complete genome sequence of Propionibacterium acnes, a commensal of human skin. Science 305, 671–673 (2004).
King, S. J. et al. Phase variable desialylation of host proteins that bind to Streptococcus pneumoniae in vivo and protect the airway. Mol. Microbiol. 54, 159–171 (2004).
Vimr, E. & Lichtensteiger, C. To sialylate, or not to sialylate: that is the question. Trends Microbiol. 10, 254–257 (2002).
Vimr, E. R., Kalivoda, K. A., Deszo, E. L. & Steenbergen, S. M. Diversity of microbial sialic acid metabolism. Microbiol. Mol. Biol. Rev. 68, 132–153 (2004).
Jorge, A. M. et al. Utilization of glycerophosphodiesters by Staphylococcus aureus. Mol. Microbiol. 103, 229–241 (2017).
Casado, B., Pannell, L. K., Iadarola, P. & Baraniuk, J. N. Identification of human nasal mucous proteins using proteomics. Proteomics 5, 2949–2959 (2005).
Tomazic, P. V. et al. Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis. J. Allergy Clin. Immunol. 133, 741–750 (2014).
Koziel, J. & Potempa, J. Protease-armed bacteria in the skin. Cell Tissue Res. 351, 325–337 (2013).
Dubin, G. et al. Molecular cloning and biochemical characterisation of proteases from Staphylococcus epidermidis. Biol. Chem. 382, 1575–1582 (2001).
Wysocki, A. B. et al. Proteolytic activity by multiple bacterial species isolated from chronic venous leg ulcers degrades matrix substrates. Biol. Res. Nurs. 15, 407–415 (2013).
Lanter, B. B. & Davies, D. G. Propionibacterium acnes recovered from atherosclerotic human carotid arteries undergoes biofilm dispersion and releases lipolytic and proteolytic enzymes in response to norepinephrine challenge in vitro. Infect. Immun. 83, 3960–3971 (2015).
Arnison, P. G. et al. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat. Prod. Rep. 30, 108–160 (2013).
Janek, D., Zipperer, A., Kulik, A., Krismer, B. & Peschel, A. High frequency and diversity of antimicrobial activities produced by nasal Staphylococcus strains against bacterial competitors. PLoS Pathog. 12, e1005812 (2016).
Bierbaum, G. & Sahl, H. G. Lantibiotics: mode of action, biosynthesis and bioengineering. Curr. Pharm. Biotechnol. 10, 2–18 (2009).
Sashihara, T. et al. A novel lantibiotic, nukacin ISK-1, of Staphylococcus warneri ISK-1: cloning of the structural gene and identification of the structure. Biosci. Biotechnol. Biochem. 64, 2420–2428 (2000).
Wilaipun, P., Zendo, T., Okuda, K., Nakayama, J. & Sonomoto, K. Identification of the nukacin KQU-131, a new type-A(II) lantibiotic produced by Staphylococcus hominis KQU-131 isolated from Thai fermented fish product (Pla-ra). Biosci. Biotechnol. Biochem. 72, 2232–2235 (2008).
Navaratna, M. A., Sahl, H. G. & Tagg, J. R. Two-component anti-Staphylococcus aureus lantibiotic activity produced by Staphylococcus aureus C55. Appl. Environ. Microbiol. 64, 4803–4808 (1998).
Navaratna, M. A., Sahl, H. G. & Tagg, J. R. Identification of genes encoding two-component lantibiotic production in Staphylococcus aureus C55 and other phage group II S. aureus strains and demonstration of an association with the exfoliative toxin B gene. Infect. Immun. 67, 4268–4271 (1999).
Nakatsuji, T. et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci. Transl Med. 9, eaah4680 (2017). This article describes how bacteriocin-producing commensals interfere with S. aureus skin colonization in patients with atopic dermatitis.
Bennallack, P. R., Burt, S. R., Heder, M. J., Robison, R. A. & Griffitts, J. S. Characterization of a novel plasmid-borne thiopeptide gene cluster in Staphylococcus epidermidis strain 115. J. Bacteriol. 196, 4344–4350 (2014).
Li, Y. M., Milne, J. C., Madison, L. L., Kolter, R. & Walsh, C. T. From peptide precursors to oxazole and thiazole-containing peptide antibiotics: microcin B17 synthase. Science 274, 1188–1193 (1996).
Netz, D. J. et al. Molecular characterisation of aureocin A70, a multi-peptide bacteriocin isolated from Staphylococcus aureus. J. Mol. Biol. 311, 939–949 (2001).
Miescher, S., Stierli, M. P., Teuber, M. & Meile, L. Propionicin SM1, a bacteriocin from Propionibacterium jensenii DF1: isolation and characterization of the protein and its gene. Syst. Appl. Microbiol. 23, 174–184 (2000).
Attia, A. S. et al. Identification of a bacteriocin and its cognate immunity factor expressed by Moraxella catarrhalis. BMC Microbiol. 9, 207 (2009).
Fujimura, S. & Nakamura, T. Purification and properties of a bacteriocin-like substance (acnecin) of oral Propionibacterium acnes. Antimicrob. Agents Chemother. 14, 893–898 (1978).
Tauch, A. et al. Complete genome sequence and analysis of the multiresistant nosocomial pathogen Corynebacterium jeikeium K411, a lipid-requiring bacterium of the human skin flora. J. Bacteriol. 187, 4671–4682 (2005).
Donia, M. S. et al. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell 158, 1402–1414 (2014).
Zipperer, A. et al. Human commensals producing a novel antibiotic impair pathogen colonization. Nature 535, 511–516 (2016). This study identifies the novel antibiotic lugdunin produced by a commensal species to exclude S. aureus from the nasal microbiome.
Heilbronner, S. et al. Genome sequence of Staphylococcus lugdunensis N920143 allows identification of putative colonization and virulence factors. FEMS Microbiol. Lett. 322, 60–67 (2011).
Bogaert, D. et al. Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet 363, 1871–1872 (2004).
Regev-Yochay, G. et al. Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in children. JAMA 292, 716–720 (2004).
Selva, L. et al. Killing niche competitors by remote-control bacteriophage induction. Proc. Natl Acad. Sci. USA 106, 1234–1238 (2009).
Uehara, Y. et al. H2O2 produced by viridans group streptococci may contribute to inhibition of methicillin-resistant Staphylococcus aureus colonization of oral cavities in newborns. Clin. Infect. Dis. 32, 1408–1413 (2001).
Lijek, R. S. et al. Protection from the acquisition of Staphylococcus aureus nasal carriage by cross-reactive antibody to a pneumococcal dehydrogenase. Proc. Natl Acad. Sci. USA 109, 13823–13828 (2012).
Hanzelmann, D. et al. Toll-like receptor 2 activation depends on lipopeptide shedding by bacterial surfactants. Nat. Commun. 7, 12304 (2016).
Riechelmann, H. et al. Nasal carriage of Staphylococcus aureus in house dust mite allergic patients and healthy controls. Allergy 60, 1418–1423 (2005).
Cole, A. M. et al. Cationic polypeptides are required for antibacterial activity of human airway fluid. J. Immunol. 169, 6985–6991 (2002).
Herbert, S. et al. Molecular basis of resistance to muramidase and cationic antimicrobial peptide activity of lysozyme in staphylococci. PLoS Pathog. 3, e102 (2007).
Bera, A. et al. Influence of wall teichoic acid on lysozyme resistance in Staphylococcus aureus. J. Bacteriol. 189, 280–283 (2007).
Hoq, M. I. & Ibrahim, H. R. Potent antimicrobial action of triclosan–lysozyme complex against skin pathogens mediated through drug-targeted delivery mechanism. Eur. J. Pharm. Sci. 42, 130–137 (2011).
Peschel, A. & Sahl, H. G. The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat. Rev. Microbiol. 4, 529–536 (2006).
Harder, J. & Schroder, J. M. RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J. Biol. Chem. 277, 46779–46784 (2002).
Lee, D. Y. et al. Sebocytes express functional cathelicidin antimicrobial peptides and can act to kill Propionibacterium acnes. J. Invest. Dermatol. 128, 1863–1866 (2008).
Cole, A. L. et al. Host innate inflammatory factors and staphylococcal protein A influence the duration of human Staphylococcus aureus nasal carriage. Mucosal Immunol. 9, 1537–1548 (2016).
Kiser, K. B., Cantey-Kiser, J. M. & Lee, J. C. Development and characterization of a Staphylococcus aureus nasal colonization model in mice. Infect. Immun. 67, 5001–5006 (1999).
Boris, M. et al. Bacterial interference; protection of adults against nasal Staphylococcus aureus infection after colonization with a heterologous S. aureus strain. Am. J. Dis. Child 108, 252–261 (1964).
Houck, P. W., Nelson, J. D. & Kay, J. L. Fatal septicemia due to Staphylococcus aureus 502A. Report of a case and review of the infectious complications of bacterial interference programs. Am. J. Dis. Child 123, 45–48 (1972).
Uehara, Y. et al. Bacterial interference among nasal inhabitants: eradication of Staphylococcus aureus from nasal cavities by artificial implantation of Corynebacterium sp. J. Hosp. Infect. 44, 127–133 (2000).
Kommineni, S. et al. Bacteriocin production augments niche competition by enterococci in the mammalian gastrointestinal tract. Nature 526, 719–722 (2015).
Schaffer, A. C. et al. Immunization with Staphylococcus aureus clumping factor B, a major determinant in nasal carriage, reduces nasal colonization in a murine model. Infect. Immun. 74, 2145–2153 (2006).
Dorrestein, P. C., Mazmanian, S. K. & Knight, R. Finding the missing links among metabolites, microbes, and the host. Immunity 40, 824–832 (2014).
Belkaid, Y. & Segre, J. A. Dialogue between skin microbiota and immunity. Science 346, 954–959 (2014).
Davis, M. F., Peng, R. D., McCormack, M. C. & Matsui, E. C. Staphylococcus aureus colonization is associated with wheeze and asthma among US children and young adults. J. Allergy Clin. Immunol. 135, 811–813.5 (2015).
Nakamura, Y. et al. Staphylococcus delta-toxin induces allergic skin disease by activating mast cells. Nature 503, 397–401 (2013).
Stentzel, S. et al. Staphylococcal serine protease-like proteins are pacemakers of allergic airway reactions to Staphylococcus aureus. J. Allergy Clin. Immunol. 139, 492–500.e8 (2017). This study reports how some S. aureus proteins lead to allergic immune reactions in human airways.
Biswas, K., Hoggard, M., Jain, R., Taylor, M. W. & Douglas, R. G. The nasal microbiota in health and disease: variation within and between subjects. Front. Microbiol. 9, 134 (2015).
Zhang, N., Van Crombruggen, K., Gevaert, E. & Bachert, C. Barrier function of the nasal mucosa in health and type-2 biased airway diseases. Allergy 71, 295–307 (2016).
Geurkink, N. Nasal anatomy, physiology, and function. J. Allergy Clin. Immunol. 72, 123–128 (1983).
de Borja Callejas, F. et al. Reconstituted human upper airway epithelium as 3D in vitro model for nasal polyposis. PLoS ONE 9, e100537 (2014).
Even-Tzur, N. et al. Air–liquid interface culture of nasal epithelial cells on denuded amniotic membranes. Cell. Mol. Bioengineer. 3, 307–318 (2010).
Becker, S. C. et al. Triple-acting lytic enzyme treatment of drug-resistant and intracellular Staphylococcus aureus. Sci. Rep. 6, 25063 (2016).
Kokai-Kun, J. F. The cotton rat as a model for Staphylococcus aureus nasal colonization in humans: cotton rat S. aureus nasal colonization model. Methods Mol. Biol. 431, 241–254 (2008).
Niewiesk, S. & Prince, G. Diversifying animal models: the use of hispid cotton rats (Sigmodon hispidus) in infectious diseases. Lab Anim. 36, 357–372 (2002).
van den Berg, S. et al. Rhesus macaques (Macaca mulatta) are natural hosts of specific Staphylococcus aureus lineages. PLoS ONE 6, e26170 (2011).
Wertheim, H. F. et al. Effect of mupirocin treatment on nasal, pharyngeal, and perineal carriage of Staphylococcus aureus in healthy adults. Antimicrob. Agents Chemother. 49, 1465–1467 (2005).
Wertheim, H. F. et al. Key role for clumping factor B in Staphylococcus aureus nasal colonization of humans. PLoS Med. 5, e17 (2008). This is the first study in human volunteers that shows the crucial role of S. aureus adhesion in nasal colonization.
Hood, M. I. & Skaar, E. P. Nutritional immunity: transition metals at the pathogen–host interface. Nat. Rev. Microbiol. 10, 525–537 (2012).
Latunde-Dada, G. O. Iron metabolism: microbes, mouse, and man. Bioessays 31, 1309–1317 (2009).
Beasley, F. C. & Heinrichs, D. E. Siderophore-mediated iron acquisition in the staphylococci. J. Inorg. Biochem. 104, 282–288 (2010).
Sebulsky, M. T., Shilton, B. H., Speziali, C. D. & Heinrichs, D. E. The role of FhuD2 in iron(iii)-hydroxamate transport in Staphylococcus aureus. Demonstration that FhuD2 binds iron(iii)-hydroxamates but with minimal conformational change and implication of mutations on transport. J. Biol. Chem. 278, 49890–49900 (2003).
Zajdowicz, S. et al. Purification and structural characterization of siderophore (corynebactin) from Corynebacterium diphtheriae. PLoS ONE 7, e34591 (2012).
Bachman, M. A., Miller, V. L. & Weiser, J. N. Mucosal lipocalin 2 has pro-inflammatory and iron-sequestering effects in response to bacterial enterobactin. PLoS Pathog. 5, e1000622 (2009).
Holden, V. I. et al. Bacterial siderophores that evade or overwhelm lipocalin 2 induce hypoxia inducible factor 1α and proinflammatory cytokine secretion in cultured respiratory epithelial cells. Infect. Immun. 82, 3826–3836 (2014).
Bachman, M. A. et al. Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2. Infect. Immun. 79, 3309–3316 (2011).
Hammer, N. D. & Skaar, E. P. The impact of metal sequestration on Staphylococcus aureus metabolism. Curr. Opin. Microbiol. 15, 10–14 (2012).
Sheldon, J. R. & Heinrichs, D. E. Recent developments in understanding the iron acquisition strategies of gram positive pathogens. FEMS Microbiol. Rev. 39, 592–630 (2015).
Heilbronner, S. et al. Competing for iron: duplication and amplification of the isd locus in Staphylococcus lugdunensis HKU09-01 provides a competitive advantage to overcome nutritional limitation. PLoS Genet. 12, e1006246 (2016).
Wilks, A. & Ikeda-Saito, M. Heme utilization by pathogenic bacteria: not all pathways lead to biliverdin. Acc. Chem. Res. 47, 2291–2298 (2014).
Karalus, R. & Campagnari, A. Moraxella catarrhalis: a review of an important human mucosal pathogen. Microbes Infect. 2, 547–559 (2000).
Tieu, D. D. et al. Evidence for diminished levels of epithelial psoriasin and calprotectin in chronic rhinosinusitis. J. Allergy Clin. Immunol. 125, 667–675 (2010).
Garcia, Y. M. et al. A superoxide dismutase capable of functioning with iron or manganese promotes the resistance of Staphylococcus aureus to calprotectin and nutritional immunity. PLoS Pathog. 13, e1006125 (2017).
Kato, T., Kouzaki, H., Matsumoto, K., Hosoi, J. & Shimizu, T. The effect of calprotectin on TSLP and IL-25 production from airway epithelial cells. Allergol Int. 66, 281–289 (2017).
Kehl-Fie, T. E. et al. MntABC and MntH contribute to systemic Staphylococcus aureus infection by competing with calprotectin for nutrient manganese. Infect. Immun. 81, 3395–3405 (2013).
Ghssein, G. et al. Biosynthesis of a broad-spectrum nicotianamine-like metallophore in Staphylococcus aureus. Science 352, 1105–1109 (2016).
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).
Author information
Authors and Affiliations
Contributions
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
Ethics declarations
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).
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.
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrmicro.2017.104
This article is cited by
-
Phytochemical screening, gas chromatograph/mass spectrometer (GCMS) analysis and molecular toxicological potential of Hunteria umbellata aqueous fruit extract against Staphylococcus aureus in accessory gene regulators (AGRs)
Future Journal of Pharmaceutical Sciences (2024)
-
Altered quorum sensing and physiology of Staphylococcus aureus during spaceflight detected by multi-omics data analysis
npj Microgravity (2024)
-
Secretory IgA impacts the microbiota density in the human nose
Microbiome (2023)
-
Molecular characterisation of Staphylococcus aureus in school-age children in Guangzhou: associations among agr types, virulence genes, sequence types, and antibiotic resistant phenotypes
BMC Microbiology (2023)
-
Systematic mining of the human microbiome identifies antimicrobial peptides with diverse activity spectra
Nature Microbiology (2023)