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A study of the genetic diversity of Streptococcus pneumoniae, the bacterium responsible for hundreds of thousands of infant deaths each year, found that deep sequencing whole pneumococcal populations gave unsurpassed sensitivity for detecting multiple colonisations and was twice as effective at detecting invasive virulent strains of the bacteria as current best methods, say researchers in a study published in Nature Microbiology.

Infants enrolled in the S. pneumoniae study at SMRU returned to the Maela camp to hear the results and celebrate © Paul Turner, 2022
Many of the infants enrolled in the S. pneumoniae study at SMRU returned to the Maela camp to hear the results and celebrate. Photo: Paul Turner. © 2022

This greater resolution identified an elevated rate of transmission from mothers to their children in the first year of the child’s life – and a clear link between antibiotic treatment and acquisition of AMR bacteria. 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.

“Large-scale whole-genome sequencing (WGS) has revolutionized surveillance of S. pneumoniae, greatly enhancing our ability to track antibiotic-resistant and vaccine-evading bacteria,” noted study co-author Prof Paul Turner, University of Oxford.

The study, Pneumococcal within-host diversity during colonization, transmission and treatment,  highlights the potential for population deep sequencing (PDS) to improve our understanding of pathogens like S. pneumoniae and to inform treatment strategies when antimicrobial resistance is a concern.

“The high resolution of this study allows us to trace the course of S. pneumoniae infection over time, finally giving us the data we need to settle questions such as how drug-susceptible and drug-resistant bacteria compete against one another. This approach shows us how, with sufficient resourcing and expertise, genomic surveillance can provide the information we need to understand the strains causing infections, and which treatments are most likely to succeed,” said Professor Stephen Bentley, a senior author of the study from the Wellcome Sanger Institute.

To test whether the full diversity of S. pneumoniae lineages present could be mapped, the researchers whole genome sequenced nasopharyngeal swab isolates collected from 965 infants and a subset of their mothers, from birth until 24 months of age, during a large longitudinal carriage study conducted by the Shoklo Malaria Research Unit (SMRU) from 2007-2010 at the Maela refugee camp on the Thai-Myanmar border.

Carried out by researchers from the Wellcome Sanger Institute, the University of Oxford, MORU, SMRU, and Imperial College London, the study suggests that the detection of such resistant variants is only possible using a population deep sequencing (PDS) approach and that their presence may be due to individuals being treated with antibiotics.

In contrast, common lineages that are susceptible to treatment were found to outcompete these multidrug resistant lineages in infants who hadn’t received antibiotic treatment.

Dr Clare Ling, a first author of the study from SMRU, Thailand, said: “Humans, particularly children, often host numerous pneumococcal strains simultaneously, which are competing with each other and with strains from other species. In a way it is good news that strains that we can treat with antibiotics are more dominant than resistant strains under normal circumstances, but the fact that treatment gives multi-drug resistant strains an advantage is concerning.”

There is a growing threat from antimicrobial resistant strains of S. pneumoniae not susceptible to commonly-used medicines, with overuse of life-saving antibiotics contributing to resistance. One way to improve our use of antibiotics is through precision medicine, population deep sequencing (PDS), where the strain causing an infection is identified so that the most appropriate drugs can be used.

Streptococcus pneumoniae, also known as the pneumococcus, is a bacterial pathogen that causes diseases ranging from ear infections through to pneumonia, septicaemia and meningitis. It is responsible for around nine million global infections annually, with elderly adults and children particularly susceptible. More than 300,000 children die from pneumococcal infection each year, mainly in low- and middle-income countries (LMICs).

- Text contributions: Matthew Midgley, Paul Turner, John Bleho.

Read the full publication, Pneumococcal within-host diversity during colonization, transmission and treatment, on the Nature Microbiology website.
Tonkin-Hill G, Ling C, Chaguza C, Salter SJ, Hinfonthong P, Nikolaou E, Tate N, Pastusiak A, Turner C, Chewapreecha C, Frost SDW, Corander J, Croucher NJ, Turner P, Bentley SD. Nat Microbiol. 2022 Oct 10. doi: 10.1038/s41564-022-01238-1. Epub ahead of print. PMID: 36216891.