Small pieces of resistance were found in pathogen diversity surveys

A new study from the Wellcome Sanger Institute, the University of Oxford, the Shocko Malaria Research Group and Imperial College London reveals the secret life of Streptococcus pneumoniae, which kills hundreds of thousands of babies every year
.

The study, published today (Oct.
10) in the journal Nature Microbiology, details the genetic diversity of pathogens in individual infants, including hidden multidrug-resistant and deadly strains
.
The findings suggest that detection of such resistant variants can only be done using population deep sequencing (PDS) methods, and their presence may be due to individuals
treated with antibiotics.
This study highlights the potential of half-death to improve our understanding of pathogens such as Streptococcus pneumoniae and inform treatment strategies for antimicrobial resistance concerns
.

Streptococcus pneumoniae, also known as pneumococcus, is a bacterial pathogen that can cause a variety of diseases
, from ear infections to pneumonia, sepsis, and meningitis.
About 9 million people worldwide are infected with malaria each year, with older people and children particularly susceptible
.
More than 300 000 children die each year from pneumococcal infections, mainly in low- and middle-income countries
.

Not all individuals parasitized by Streptococcus pneumoniae get sick
.
Up to 60% of children2 carry this bacteria without symptoms, and even smaller
percentages of adults carry this bacteria.
Children are often parasitized by common strains, which allows our immune system to recognize and guard against them
.
As adults, we tend to be overwhelmed
by rare strains that we have never seen before.

In the new study, researchers at the Wellcome Sanger Institute, the University of Oxford and Imperial College set out to document the diversity
of Streptococcus pneumoniae in children and adults.

Over a two-year period, nearly 4,000 samples were collected from infants and mothers and sequenced their whole genomes to test whether they could map the full diversity
of the Streptococcus pneumoniae lineage.
Similar to previous studies, common serotypes such as 19F and 23F are more likely to be found in infants4
.
Serotype 3 is the only one that causes disease in adults and is more common
in mothers.

Importantly, this genomics-based approach increases sensitivity compared to standard tests, indicating the presence of rarer disease-associated serotypes in infants, but at lower
levels.

Dr Gerry Tonkin-Hill of the Wellcome Sanger Institute, who is the study's first author, said: "Most bacterial studies only look at one genome for each person, but this means that the full diversity of the bacteria we live in is not being
recorded.
We wanted to see what
we missed by analyzing multiple genomes extracted from the same person at the same time.
The results of this study confirm that whole genome sequencing of bacterial genomic populations is a highly accurate and efficient method, as evidenced
by the detection of a small number of disease-associated serotypes in infants.
”

The genome sequence data was also compared
with the antibiotic treatment received by the diseased individuals participating in the study.
The analysis showed that infants were at higher
risk of colonization by the multidrug resistance spectrum after treatment.

In contrast, the study found that in infants not treated with antibiotics, the common lineage susceptible to treatment was more competitive
than these multidrug-resistant ancestry.

Dr Clare Ling, lead author of the study, from the Shoklo Malaria Study in Thailand, said: "Humans, especially children, often carry large numbers of pneumococcal strains at the same time, which compete
with each other and with strains of other species.
To some extent, under normal circumstances, the strains we can treat with antibiotics are more dominant than resistant strains is good news, but the fact that treatment gives multidrug-resistant strains an advantage is worrying
.
”

Similar to other pathogens that regularly infect humans, drug-resistant strains of Streptococcus pneumoniae that are not sensitive to commonly used drugs are
increasingly threatening.
Overuse of antibiotics is thought to lead to drug resistance, but these drugs save lives and remain our best defense
against infectious bacteria.
One way to improve antibiotic use is through precision medicine, i.
e.
identifying the strain causing the infection so that the most appropriate drug
can be used.

The high resolution of this study allows us to trace the course of Streptococcus pneumoniae infection, ultimately giving us the data we need to solve problems such as how drug-sensitive and drug-resistant bacteria compete with each other
.
This approach shows us that, with sufficient resources and expertise, genomic monitoring can give us the information
we need to unravel the strain causing the infection and which treatment is most likely to succeed.

Pneumococcal within-host diversity during colonisation, transmission and treatment