Isolate differences in colonization efficiency during experimental human pneumococcal challenge

Colonization efficiency varies considerably between Streptococcus pneumoniae (pneumococcus) strains. The microbial characteristics that influence those differences are still largely unknown. Here, we report rates and kinetics of colonization of four pneumococcal strains upon experimental human pneumococcal challenge. Healthy adults were intranasally challenged with one of four pneumococcal strains (serotype/clonal name: 6B/BHN418, 15B/SH8286, 23F/P1121 and 23F/P833) over a range of doses. Maximum colonization achieved was 60%, 31%, 16% and 10%, respectively. Density and duration of colonization did not differ significantly between the tested strains. We further evaluated murine colonization, non-opsonic neutrophil mediated killing, epithelial cell adherence and average chain length of these four pneumococcal strains. Of these, only chain length was found to be associated with colonization efficiency in the human challenge model. Our data demonstrate that colonization rates following experimental challenge vary with the strain used and suggest that efficiency in colonization is related to pneumococcal chain length. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ISRCTN85403723 (11/NW/0592) ; [ISRCTN68323432][1] (15/NW/0931) ### Funding Statement The work was supported by the Bill and Melinda Gates Foundation (GCE award to SBG, no: OPP1035281 and grant award to DMF OPP1117728), the Medical Research Council to SBG and DF (grant MR/M011569/1) and the National Institute for Health Research Comprehensive Local Research Network. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The study was co-sponsored by the Royal Liverpool and Broadgreen University Hospitals NHS trust and the Liverpool School of Tropical Medicine. JNW was supported by grants from the U.S. Public Health Service (RO1 AI05168 and RO1 AI38446). Confocal imaging facilities were funded by a Wellcome Trust Multi-User Equipment Grant (104936/Z/14/Z). ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Nucleotide sequence of the challenge isolate 6B/BHN418 can be accessed in GenBank under accession numbers ASHP00000000.1. Nucleotide sequence of the challenge strains 23F/P833, 23F/P1121, and 15B/SH8286 can be accessed in the European Nucleotide Archive (ENA) using the following accession numbers: for 23F/P833 - ERS743506, for 23F/P1121 - ERS1072059 and for 15B/SH8286 - ERS2632437. The source data for figures displayed in this paper are available from the corresponding author on request. This study did not generate new unique reagents. Further information and requests regarding resource availability concerning this study should be directed to the Lead Contact, Prof. Daniela Ferreira (daniela.ferreira@lstmed.ac.uk). [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN68323432