The genetic diversity of Streptococcus pneumoniae, the bacterium responsible for hundreds of thousands of infant deaths each year, has been unravelled for the first time, it was announced last night.
The findings from the Wellcome Sanger Institute, the University of Oxford, Imperial College London, UK, and the Shoklo Malaria Research Unit in Thailand, including hidden multidrug-resistant and virulent strains, suggest it is only possible to detect such resistant variants using a population deep sequencing (PDS) approach.
The researchers also believe the virulent strains may only be present because the individuals concerned were treated with antibiotics.
The study, published in the latest edition of *Nature Microbiology*, highlights the potential for PDS to improve understanding of pathogens such as S. pneumoniae and to inform treatment strategies when antimicrobial resistance is a concern.
Streptococcus pneumoniae, also known as the pneumococcus, is a bacterial pathogen that causes diseases ranging from ear infections through to pneumonia, septicaemia and meningitis.
In this new study, researchers at the Wellcome Sanger Institute, the University of Oxford and Imperial College London set out to document the diversity of S. pneumoniae in children and adults.
They collected almost 4,000 samples from infants and mothers over two years two-year period, which were whole genome sequenced to establish if the full diversity of S. pneumoniae lineages present could be mapped.
As was found in previous studies, common serotypes such as 19F and 23F were much more likely to be found in infants, while serotype 3, which is responsible for disease in adults, was the only one to be found more frequently in mothers.
First study author Dr Gerry Tonkin-Hill, from the Wellcome Sanger Institute, said: "Most bacterial studies only look at one genome per person, but this means that the full diversity of the bacteria that we’re colonised by goes unrecorded.
"We wanted to see what we were missing by analysing many genomes taken from the same person simultaneously. The results of this study confirm that whole genome sequencing of populations of bacterial genomes is a highly accurate and effective way to do this, as shown by the detection of low numbers of disease-linked serotypes in infants."�
They also compared genomic sequence data to antibiotic treatments that individuals received while taking part in the study, finding that infants had a higher risk of being colonised by multidrug resistant lineages following treatment.
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, first study author from Shoklo Malaria Research Unit, Thailand, added: "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."�
Senior study author Professor Stephen Bentley, from the Wellcome Sanger Institute, said the high resolution of the study allowed them to trace the course of S. pneumoniae infection over time.
This enabled them to collect data that could help them answer questions about 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,"� he added.
Gerry Tonkin-Hill and Clare Ling et al. (2022). Pneumococcal within-host diversity during colonisation, transmission and treatment. Nature Microbiology
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