Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy


Streptococcus pneumoniae (pneumococcus) is a leading cause of severe infections among children and adults. Interactions between commensal microbes in the upper respiratory tract and S. pneumoniae are poorly described. In this study, we sought to identify interspecies interactions that modify the risk of S. pneumoniae colonization during infancy and to describe development of the upper respiratory microbiome during infancy in a sub-Saharan African setting. We collected nasopharyngeal swabs monthly (0–6 months of age) or bimonthly (6–12 months of age) from 179 mother–infant dyads in Botswana. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and identified S. pneumoniae colonization using a species-specific PCR assay. We detect S. pneumoniae colonization in 144 (80%) infants at a median age of 71 days and identify a strong negative association between the relative abundance of the bacterial genera Corynebacterium within the infant nasopharyngeal microbiome and the risk of S. pneumoniae colonization. Using in vitro cultivation experiments, we demonstrate growth inhibition of S. pneumoniae by secreted factors from strains of several Corynebacterium species isolated from these infants. Finally, we demonstrate that antibiotic exposures and the winter season are associated with a decline in the relative abundance of Corynebacterium within the nasopharyngeal microbiome, while breastfeeding is associated with an increase in the Corynebacterium relative abundance. Our findings provide novel insights into the interspecies interactions that contribute to colonization resistance to S. pneumoniae and suggest that the nasopharyngeal microbiome may be a previously unrecognized mechanism by which environmental factors influence the risk of pneumococcal infections during childhood. Moreover, this work lays the foundation for future studies seeking to use targeted manipulation of the nasopharyngeal microbiome to prevent infections caused by S. pneumoniae.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Alpha diversity of the nasopharyngeal microbiome among mother–infant dyads in Botswana.
Fig. 2: Composition of the nasopharyngeal microbiome among mother–infant dyads in Botswana.
Fig. 3: State transitions of the nasopharyngeal microbiome during infancy.
Fig. 4: Associations between environmental exposures and the composition of the nasopharyngeal microbiome during infancy.
Fig. 5: Strain-specific inhibition of pneumococcal growth by Corynebacterium.

Availability of data and materials

The sequencing dataset supporting the conclusions of this study is available in the Sequence Read Archive (PRJNA698366). The statistical files and script used for data analyses are also publicly available (


  1. 1.

    Backhaus E, Berg S, Andersson R, Ockborn G, Malmström P, Dahl M, et al. Epidemiology of invasive pneumococcal infections: manifestations, incidence and case fatality rate correlated to age, gender and risk factors. BMC Infect Dis. 2016;16:367.

    PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Bogaert D, de Groot R, Hermans P. Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis. 2004;4:144–54.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Wahl B, O’Brien KL, Greenbaum A, Majumder A, Liu L, Chu Y, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15. Lancet Glob Health. 2018;6:e744–57.

    PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    McAllister DA, Liu L, Shi T, Chu Y, Reed C, Burrows J, et al. Global, regional, and national estimates of pneumonia morbidity and mortality in children younger than 5 years between 2000 and 2015: a systematic analysis. Lancet Glob Health. 2019;7:e47–57.

    PubMed  Article  Google Scholar 

  5. 5.

    Abdullahi O, Karani A, Tigoi CC, Mugo D, Kungu S, Wanjiru E, et al. The prevalence and risk factors for pneumococcal colonization of the nasopharynx among children in Kilifi District, Kenya. PloS ONE. 2012;7:e30787.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  6. 6.

    Kelly MS, Surette MG, Smieja M, Rossi L, Luinstra K, Steenhoff AP, et al. Pneumococcal colonization and the nasopharyngeal microbiota of children in Botswana. Pediatr Infect Dis J. 2018;37:1176–83.

    PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Huang SS, Hinrichsen VL, Stevenson AE, Rifas-Shiman SL, Kleinman K, Pelton SI, et al. Continued impact of pneumococcal conjugate vaccine on carriage in young children. Pediatrics 2009;124:e1–e11.

    PubMed  Article  Google Scholar 

  8. 8.

    van Hoek AJ, Sheppard CL, Andrews NJ, Waight PA, Slack MP, Harrison TG, et al. Pneumococcal carriage in children and adults two years after introduction of the thirteen valent pneumococcal conjugate vaccine in England. Vaccine.2014;32:4349–55.

    PubMed  Article  Google Scholar 

  9. 9.

    Almeida ST, Nunes S, Paulo ACS, Valadares I, Martins S, Breia F, et al. Low prevalence of pneumococcal carriage and high serotype and genotype diversity among adults over 60 years of age living in Portugal. PloS ONE 2014;9:e90974.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  10. 10.

    Kaplan SL, Mason EO, Wald ER, Schutze GE, Bradley JS, Tan TQ, et al. Decrease of invasive pneumococcal infections in children among 8 children’s hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine. Pediatrics.2004;113:443–9.

    PubMed  Article  Google Scholar 

  11. 11.

    Hammitt LL, Etyang AO, Morpeth SC, Ojal J, Mutuku A, Mturi N, et al. Effect of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease and nasopharyngeal carriage in Kenya: a longitudinal surveillance study. Lancet.2019;393:2146–54.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  12. 12.

    Cutts F, Zaman S, Enwere GY, Jaffar S, Levine O, Okoko J, et al. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. Lancet.2005;365:1139–46.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Congdon M, Hong H, Young RR, Cunningham CK, Enane LA, Arscott-Mills T, et al. Effect of Haemophilus influenzae type b and 13-valent pneumococcal conjugate vaccines on childhood pneumonia hospitalizations and deaths in Botswana. Clin Infect Dis. 2020; e-pub ahead of print 8 July 2020;

  14. 14.

    Eskola J, Kilpi T, Palmu A, Jokinen J, Eerola M, Haapakoski J, et al. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N. Engl J Med. 2001;344:403–9.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Pelton SI, Huot H, Finkelstein JA, Bishop CJ, Hsu KK, Kellenberg J, et al. Emergence of 19A as virulent and multidrug resistant Pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2007;26:468–72.

    PubMed  Article  Google Scholar 

  16. 16.

    Pichichero ME, Casey JR. Emergence of a multiresistant serotype 19A pneumococcal strain not included in the 7-valent conjugate vaccine as an otopathogen in children. JAMA.2007;298:1772–8.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Neves FP, Cardoso NT, Snyder RE, Marlow MA, Cardoso CA, Teixeira LM, et al. Pneumococcal carriage among children after four years of routine 10-valent pneumococcal conjugate vaccine use in Brazil: the emergence of multidrug resistant serotype 6C. Vaccine.2017;35:2794–800.

    PubMed  Article  Google Scholar 

  18. 18.

    Bradshaw JL, McDaniel LS. Selective pressure: rise of the nonencapsulated pneumococcus. PLoS Pathog. 2019;15:e1007911.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  19. 19.

    Ladhani SN, Collins S, Djennad A, Sheppard CL, Borrow R, Fry NK, et al. Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000–17: a prospective national observational cohort study. Lancet Infect Dis. 2018;18:441–51.

    PubMed  Article  Google Scholar 

  20. 20.

    Ouldali N, Levy C, Varon E, Bonacorsi S, Béchet S, Cohen R, et al. Incidence of paediatric pneumococcal meningitis and emergence of new serotypes: a time-series analysis of a 16-year French national survey. Lancet Infect Dis. 2018;18:983–91.

    PubMed  Article  Google Scholar 

  21. 21.

    Zaneveld J, Turnbaugh PJ, Lozupone C, Ley RE, Hamady M, Gordon JI, et al. Host-bacterial coevolution and the search for new drug targets. Curr Opin Chem Biol. 2008;12:109–14.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  22. 22.

    de Steenhuijsen Piters WA, Binkowska J, Bogaert D. Early life microbiota and respiratory tract infections. Cell Host Microbe. 2020;28:223–32.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Bogaert D, van Belkum A, Sluijter M, Luijendijk A, de Groot R, Rümke H, et al. Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet.2004;363:1871–2.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Pettigrew MM, Gent JF, Revai K, Patel JA, Chonmaitree T. Microbial interactions during upper respiratory tract infections. Emerg Infect Dis. 2008;14:1584.

    PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Shiri T, Nunes MC, Adrian PV, Van Niekerk N, Klugman KP, Madhi SA. Interrelationship of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus colonization within and between pneumococcal-vaccine naïve mother–child dyads. BMC Infect Dis. 2013;13:483.

    PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    Jacoby P, Watson K, Bowman J, Taylor A, Riley TV, Smith DW, et al. Modelling the co-occurrence of Streptococcus pneumoniae with other bacterial and viral pathogens in the upper respiratory tract. Vaccine.2007;25:2458–64.

    PubMed  Article  Google Scholar 

  27. 27.

    Nzenze S, Shiri T, Nunes M, Klugman K, Kahn K, Twine R, et al. Temporal association of infant immunisation with pneumococcal conjugate vaccine on the ecology of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonisation in a rural South African community. Vaccine.2014;32:5520–30.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Faden H, Stanievich J, Brodsky L, Bernstein J, Ogra PL. Changes in nasopharyngeal flora during otitis media of childhood. Pediatr Infect Dis J. 1990;9:623–6.

    PubMed  CAS  Google Scholar 

  29. 29.

    Shekhar S, Khan R, Schenck K, Petersen FC. Intranasal Immunization with the commensal Streptococcus mitis confers protective immunity against pneumococcal lung infection. Appl Environ Microbiol. 2019;85:e02235–18.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  30. 30.

    Cangemi de Gutierrez R, Santos V, Nader-Macias ME. Protective effect of intranasally inoculated Lactobacillus fermentum against Streptococcus pneumoniae challenge on the mouse respiratory tract. FEMS Immunol Med Microbiol. 2001;31:187–95.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Wong SS, Quan Toh Z, Dunne EM, Mulholland EK, Tang ML, Robins-Browne RM, et al. Inhibition of Streptococcus pneumoniae adherence to human epithelial cells in vitro by the probiotic Lactobacillus rhamnosus GG. BMC Res Notes. 2013;6:135.

    PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Laufer AS, Metlay JP, Gent JF, Fennie KP, Kong Y, Pettigrew MM. Microbial communities of the upper respiratory tract and otitis media in children. mBio.2011;2:e00245–10.

    PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Bomar L, Brugger SD, Yost BH, Davies SS, Lemon KP. Corynebacterium accolens releases antipneumococcal free fatty acids from human nostril and skin surface triacylglycerols. mBio.2016;7:e01725–15.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  34. 34.

    Cope EK, Goldstein-Daruech N, Kofonow JM, Christensen L, McDermott B, Monroy F, et al. Regulation of virulence gene expression resulting from Streptococcus pneumoniae and nontypeable Haemophilus influenzae interactions in chronic disease. PloS ONE. 2011;6:e28523.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  35. 35.

    Lysenko ES, Ratner AJ, Nelson AL, Weiser JN. The role of innate immune responses in the outcome of interspecies competition for colonization of mucosal surfaces. PloS Pathog. 2005;1:e1.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  36. 36.

    Weimer KE, Juneau RA, Murrah KA, Pang B, Armbruster CE, Richardson SH, et al. Divergent mechanisms for passive pneumococcal resistance to β-lactam antibiotics in the presence of Haemophilus influenzae. J Infect Dis. 2011;203:549–55.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  37. 37.

    Tikhomirova A, Kidd SP. Haemophilus influenzae and Streptococcus pneumoniae: living together in a biofilm. Pathog Dis. 2013;69:114–26.

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Brugger SD, Eslami SM, Pettigrew MM, Escapa IF, Henke MT, Kong Y, et al. Dolosigranulum pigrum cooperation and competition in human nasal microbiota. mSphere. 2020;5.

  39. 39.

    Teo SM, Mok D, Pham K, Kusel M, Serralha M, Troy N, et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe. 2015;17:704–15.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  40. 40.

    Mika M, Mack I, Korten I, Qi W, Aebi S, Frey U, et al. Dynamics of the nasal microbiota in infancy: a prospective cohort study. J Allergy Clin Immunol. 2015;135:905–12.

    PubMed  Article  Google Scholar 

  41. 41.

    Biesbroek G, Tsivtsivadze E, Sanders EA, Montijn R, Veenhoven RH, Keijser BJ, et al. Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am J Respir Crit Care Med. 2014;190:1283–92.

    PubMed  Article  PubMed Central  Google Scholar 

  42. 42.

    Bosch AA, Levin E, van Houten MA, Hasrat R, Kalkman G, Biesbroek G, et al. Development of upper respiratory tract microbiota in infancy is affected by mode of delivery. EBioMedicine.2016;9:336–45.

    PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA. 2010;107:11971–5.

    PubMed  PubMed Central  Article  Google Scholar 

  44. 44.

    Biesbroek G, Bosch AA, Wang X, Keijser BJ, Veenhoven RH, Sanders EA, et al. The impact of breastfeeding on nasopharyngeal microbial communities in infants. Am J Respir Crit Care Med. 2014;190:298–308.

    PubMed  Article  Google Scholar 

  45. 45.

    Bogaert D, Keijser B, Huse S, Rossen J, Veenhoven R, Van Gils E, et al. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PloS ONE. 2011;6:e17035.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  46. 46.

    Bruce N, Perez-Padilla R, Albalak R. Indoor air pollution in developing countries: a major environmental and public health challenge. Bull World Health Organ. 2000;78:1078–92.

    PubMed  PubMed Central  CAS  Google Scholar 

  47. 47.

    Pelissari DM, Diaz-Quijano FA. Household crowding as a potential mediator of socioeconomic determinants of tuberculosis incidence in Brazil. PloS ONE. 2017;12:e0176116.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  48. 48.

    Mannucci PM, Franchini M. Health effects of ambient air pollution in developing countries. Int J Environ Res Public Health. 2017;14:1048.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  49. 49.

    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature.2012;486:222–7.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  50. 50.

    Ferretti P, Pasolli E, Tett A, Asnicar F, Gorfer V, Fedi S, et al. Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host Microbe. 2018;24:133–45.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  51. 51.

    Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA. 2011;108:4680–7.

    PubMed  Article  Google Scholar 

  52. 52.

    Mallick H, Rahnavard A, McIver LJ, Ma S, Zhang Y, Nguyen LH, et al. Multivariable association discovery in population-scale meta-omics studies. bioRxiv. 2021.

  53. 53.

    Hojsak I, Snovak N, Abdović S, Szajewska H, Mišak Z, Kolaček S. Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2010;29:312–6.

    PubMed  Article  Google Scholar 

  54. 54.

    Gluck U, Gebbers JO. Ingested probiotics reduce nasal colonization with pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and beta-hemolytic streptococci). Am J Clin Nutr. 2003;77:517–20.

    PubMed  Article  CAS  Google Scholar 

  55. 55.

    Feleszko W, Jaworska J, Rha RD, Steinhausen S, Avagyan A, Jaudszus A, et al. Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma. Clin Exp Allergy. 2007;37:498–505.

    PubMed  Article  CAS  Google Scholar 

  56. 56.

    Nhan T-X, Parienti J-J, Badiou G, Leclercq R, Cattoir V. Microbiological investigation and clinical significance of Corynebacterium spp. in respiratory specimens. Diagn Microbiol Infect Dis. 2012;74:236–41.

    PubMed  Article  Google Scholar 

  57. 57.

    Díez-Aguilar M, Ruiz-Garbajosa P, Fernández-Olmos A, Guisado P, Del Campo R, Quereda C, et al. Non-diphtheriae Corynebacterium species: an emerging respiratory pathogen. Eur J Clin Microbiol Infect Dis. 2013;32:769–72.

    PubMed  Article  CAS  Google Scholar 

  58. 58.

    Teutsch B, Berger A, Marosevic D, Schönberger K, Lâm T-T, Hubert K, et al. Corynebacterium species nasopharyngeal carriage in asymptomatic individuals aged ≥ 65 years in Germany. Infection.2017;45:607–11.

    PubMed  Article  CAS  Google Scholar 

  59. 59.

    Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, et al. BLAST+: architecture and applications. BMC Bioinforma. 2009;10:421.

    Article  CAS  Google Scholar 

  60. 60.

    Turner P, Turner C, Green N, Ashton L, Lwe E, Jankhot A, et al. Serum antibody responses to pneumococcal colonization in the first 2 years of life: results from an SE Asian longitudinal cohort study. Clin Microbiol Infect. 2013;19:e551–8.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  61. 61.

    Numminen E, Chewapreecha C, Turner C, Goldblatt D, Nosten F, Bentley SD, et al. Climate induces seasonality in pneumococcal transmission. Sci Rep. 2015;5:11344.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  62. 62.

    Kelly MS, Smieja M, Luinstra K, Wirth KE, Goldfarb DM, Steenhoff AP, et al. Association of respiratory viruses with outcomes of severe childhood pneumonia in Botswana. PloS ONE. 2015;10:e0126593.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  63. 63.

    le Roux DM, Myer L, Nicol MP, Zar HJ. Incidence and severity of childhood pneumonia in the first year of life in a South African birth cohort: the Drakenstein Child Health Study. Lancet Glob Health. 2015;3:e95–103.

    PubMed  Article  Google Scholar 

  64. 64.

    von Mollendorf C, von Gottberg A, Tempia S, Meiring S, de Gouveia L, Quan V, et al. Increased risk and mortality of invasive pneumococcal disease in HIV-exposed-uninfected infants <1 year of age in South Africa, 2009-2013. Clin Infect Dis. 2015;60:1346–56.

    Article  Google Scholar 

  65. 65.

    Farley JJ, King JC Jr., Nair P, Hines SE, Tressler RL, Vink PE. Invasive pneumococcal disease among infected and uninfected children of mothers with human immunodeficiency virus infection. J Pediatr. 1994;124:853–8.

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    Kinabo GD, van der Ven A, Msuya LJ, Shayo AM, Schimana W, Ndaro A, et al. Dynamics of nasopharyngeal bacterial colonisation in HIV-exposed young infants in Tanzania. Trop Med Int Health. 2013;18:286–95.

    PubMed  CAS  Google Scholar 

  67. 67.

    Koliou MG, Andreou K, Lamnisos D, Lavranos G, Iakovides P, Economou C, et al. Risk factors for carriage of Streptococcus pneumoniae in children. BMC Pediatr. 2018;18:1–8.

    Article  CAS  Google Scholar 

  68. 68.

    List of prokaryotic names with standing in nomenclature. Available at: Accessed 4 February 2021.

  69. 69.

    Efstratiou A, George R. Microbiology and epidemiology of diphtheria. Rev Med Microbiol. 1996;7:31–42.

    Article  Google Scholar 

  70. 70.

    Spach DH, Opp DR, Gabre-Kidan T. Bacteremia due to Corynebacterium jeikeium in a patient with AIDS. Rev Infect Dis. 1991;13:342–3.

    PubMed  Article  CAS  Google Scholar 

  71. 71.

    Wang C, Mattson D, Wald A. Corynebacterium jeikeium bacteremia in bone marrow transplant patients with Hickman catheters. Bone Marrow Transplant. 2001;27:445.

    PubMed  Article  CAS  Google Scholar 

  72. 72.

    Morris A, Guild I. Endocarditis due to Corynebacterium pseudodiphtheriticum: five case reports, review, and antibiotic susceptibilities of nine strains. Rev Infect Dis. 1991;13:887–92.

    PubMed  Article  CAS  Google Scholar 

  73. 73.

    Bookani KR, Marcus R, Cheikh E, Parish M, Salahuddin U. Corynebacterium jeikeium endocarditis: a case report and comprehensive review of an underestimated infection. IDCases.2018;11:26–30.

    Article  Google Scholar 

  74. 74.

    Renom F, Gomila M, Garau M, Gallegos M, Guerrero D, Lalucat J, et al. Respiratory infection by Corynebacterium striatum: epidemiological and clinical determinants. N. Microbes N. Infect. 2014;2:106–14.

    Article  CAS  Google Scholar 

  75. 75.

    Bittar F, Cassagne C, Bosdure E, Stremler N, Dubus J-C, Sarles J, et al. Outbreak of Corynebacterium pseudodiphtheriticum infection in cystic fibrosis patients, France. Emerg Inf Dis. 2010;16:1231.

    Article  CAS  Google Scholar 

  76. 76.

    Stubbendieck RM, May DS, Chevrette MG, Temkin MI, Wendt-Pienkowski E, Cagnazzo J, et al. Competition among nasal bacteria suggests a role for siderophore-mediated interactions in shaping the human nasal microbiota. Appl Environ Microbiol. 2019;85:e02406–18.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  77. 77.

    Kiryukhina N, Melnikov V, Suvorov A, Morozova YA, Ilyin V. Use of Corynebacterium pseudodiphtheriticum for elimination of Staphylococcus aureus from the nasal cavity in volunteers exposed to abnormal microclimate and altered gaseous environment. Probiotics Antimicrob Proteins. 2013;5:233–8.

    PubMed  Article  CAS  Google Scholar 

  78. 78.

    Lappan R, Peacock CS. Corynebacterium and Dolosigranulum: future probiotic candidates for upper respiratory tract infections. Microbiol Aust. 2019;40:172–7.

    Google Scholar 

  79. 79.

    Neal EFG, Nguyen C, Ratu FT, Matanitobua S, Dunne EM, Reyburn R, et al. A comparison of pneumococcal nasopharyngeal carriage in very young Fijian infants born by vaginal or cesarean delivery. JAMA Netw Open. 2019;2:e1913650.

    PubMed  PubMed Central  Article  Google Scholar 

  80. 80.

    UN Interagency Group for Child Mortality Estimation. Levels & trends in child mortality, report 2020. Available at: Accessed 3 Nov 2020.

  81. 81.

    United Nations Children’s Fund, World Health Organization. Botswana: WHO and UNICEF estimates of immunization coverage, 2019 revision. Available at: Accessed 18 Jan 2021.

  82. 82.

    Statistics Botswana. 2011 Population and Housing Census Analytical Report. Available at: Accessed 24 July 2016.

  83. 83.

    Joint United Nations Programme on HIV/AIDS. UNAIDS estimates 2019: Botswana. Available at: Accessed 3 Feb 2021.

  84. 84.

    McAvin JC, Reilly PA, Roudabush RM, Barnes WJ, Salmen A, Jackson GW, et al. Sensitive and specific method for rapid identification of Streptococcus pneumoniae using real-time fluorescence PCR. J Clin Microbiol. 2001;39:3446–51.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  85. 85.

    Gueye SB, Diop-Ndiaye H, Diallo MM, Ly O, Sow-Ndoye A, Diagne-Gueye ND, et al. Performance of Roche CAP/CTM HIV-1 qualitative test version 2.0 using dried blood spots for early infant diagnosis. J Virol Methods. 2016;229:12–15.

    PubMed  Article  CAS  Google Scholar 

  86. 86.

    Gilbert JA, Meyer F, Antonopoulos D, Balaji P, Brown CT, Brown CT, et al. Meeting report: the terabase metagenomics workshop and the vision of an Earth microbiome project. Stand Genom Sci. 2010;3:243–8.

    Article  Google Scholar 

  87. 87.

    Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics.2014;30:2114–20.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  88. 88.

    Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–6.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  89. 89.

    Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13:581.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  90. 90.

    Escapa IF, Huang Y, Chen T, Lin M, Kokaras A, Dewhirst FE, et al. Construction of habitat-specific training sets to achieve species-level assignment in 16S rRNA gene datasets. Microbiome.2020;8:1–16.

    Article  Google Scholar 

  91. 91.

    Davis NM, Proctor DM, Holmes SP, Relman DA, Callahan BJ. Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome.2018;6:226.

    PubMed  PubMed Central  Article  Google Scholar 

  92. 92.

    McMurdie PJ, Holmes S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PloS ONE. 2013;8:e61217.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  93. 93.

    Oksanen J, Kindt R, Legendre P, O’Hara B, Stevens MHH, Oksanen MJ, et al. The vegan package. Community Ecol Package. 2007;10:719.

    Google Scholar 

  94. 94.

    Anderson MJ. A new method for non‐parametric multivariate analysis of variance. Austral Ecol. 2001;26:32–46.

    Google Scholar 

  95. 95.

    Biesbroek G, Wang X, Keijser BJ, Eijkemans RM, Trzcinski K, Rots NY, et al. Seven-valent pneumococcal conjugate vaccine and nasopharyngeal microbiota in healthy children. Emerg Infect Dis. 2014;20:201–10.

    PubMed  PubMed Central  Article  Google Scholar 

  96. 96.

    Bender JM, Li F, Martelly S, Byrt E, Rouzier V, Leo M, et al. Maternal HIV infection influences the microbiome of HIV-uninfected infants. Sci Transl Med. 2016;8:349ra100.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  97. 97.

    Rosas-Salazar C, Shilts MH, Tovchigrechko A, Schobel S, Chappell JD, Larkin EK, et al. Differences in the nasopharyngeal microbiome during acute respiratory tract infection with human rhinovirus and respiratory syncytial virus in infancy. J Infect Dis. 2016;214:1924–8.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  98. 98.

    Therneau T. A package for survival analysis in R. R package version 3.2.11,

Download references


We would like to thank Copan Italia (Brescia, Italy) for the donation of the MSwab media and flocked swabs used in the collection of nasopharyngeal specimens. We also thank the Duke University School of Medicine for the use of the Microbiome Core Facility, which performed the DNA extractions for this research. We offer sincere gratitude to the children and families who participated in this research.


This research was supported by a Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases, by Children’s Hospital of Philadelphia and the Pincus Family Foundation, and through core services from the Penn Center for AIDS Research, a National Institutes of Health (NIH)-funded program (P30-AI045008). MSK and CKC received financial support from the NIH through the Duke Center for AIDS Research (P30-AI064518). MSK was supported by a NIH Career Development Award (K23-AI135090) and a research grant from the Society for Pediatric Research. PCS received funding from the NIH through a Research Project Grant (7R01-GM108494). SMP was supported by a VECD Global Health Fellowship, funded by the Office of AIDS Research and the Fogarty International Center of the NIH (D43-TW009337). APS and TAM received financial support from the NIH through the Penn Center for AIDS Research (P30-AI045008).

Author information




MSK, APS, TA, KAF, JFR SSS, CKC and PCS contributed to the study concept and design. MSK, CP, YY, JNA, SMP, JHH, RRY, MS, SB, TL, TM, MZP, JJ, CRP collected the data or assisted with data analysis or interpretation. MSK drafted the paper and all other authors revised it critically for important intellectual content. All authors approved of the final version of the paper.

Corresponding author

Correspondence to Matthew S. Kelly.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by the Botswana Ministry of Health, the Princess Marina Hospital ethics committee, and institutional review boards at the University of Pennsylvania, Duke University, and McMaster University. Written informed consent was obtained from all participants or their legal guardians.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kelly, M.S., Plunkett, C., Yu, Y. et al. Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy. ISME J (2021).

Download citation


Quick links