Pneumococcal within-host diversity during colonization, transmission and treatment

Tonkin-Hill, Gerry, Ling, Clare, Chaguza, Chrispin, Salter, Susannah J., Hinfonthong, Pattaraporn, Nikolaou, Elissavet, Tate, Natalie, Pastusiak, Andrzej, Turner, Claudia, Chewapreecha, Claire, Frost, Simon D. W., Corander, Jukka, Croucher, Nicholas J., Turner, Paul and Bentley, Stephen D. (2022) 'Pneumococcal within-host diversity during colonization, transmission and treatment'. Nature Microbiology, Vol 7, Issue 11, pp. 1791-1804.

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Abstract

Characterizing the genetic diversity of pathogens within the host promises to greatly improve surveillance and reconstruction of transmission chains. For bacteria, it also informs our understanding of inter-strain competition and how this shapes the distribution of resistant and sensitive bacteria. Here we study the genetic diversity of Streptococcus pneumoniae within 468 infants and 145 of their mothers by deep sequencing whole pneumococcal populations from 3,761 longitudinal nasopharyngeal samples. We demonstrate that deep sequencing has unsurpassed sensitivity for detecting multiple colonization, doubling the rate at which highly invasive serotype 1 bacteria were detected in carriage compared with gold-standard methods. The greater resolution identified an elevated rate of transmission from mothers to their children in the first year of the child’s life. Comprehensive treatment data demonstrated that infants were at an elevated risk of both the acquisition and persistent colonization of a multidrug-resistant bacterium following antimicrobial treatment. Some alleles were enriched after antimicrobial treatment, suggesting that they aided persistence, but generally purifying selection dominated within-host evolution. Rates of co-colonization imply that in the absence of treatment, susceptible lineages outcompeted resistant lineages within the host. These results demonstrate the many benefits of deep sequencing for the genomic surveillance of bacterial pathogens.

Item Type:	Article
Subjects:	WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 200 Bacterial infections (General or not elsewhere classified) WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 210 Streptococcal infections (General or not elsewhere classified) WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/s41564-022-01238-1
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	17 Nov 2022 13:35
Last Modified:	13 Jun 2023 11:07
URI:	https://archive.lstmed.ac.uk/id/eprint/21378

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