Abstract
BackgroundStreptococcus pneumoniae or pneumococcus is a leading cause of morbidity and mortality worldwide, specifically in relation to community-acquired pneumonia. Due to the overuse of antibiotics, S. pneumoniae has developed a high degree of resistance to a wide range of antibacterial drugs.MethodsIn this study, whole genome sequencing (WGS) was performed for 10 clinical strains of S. pneumoniae with different levels of sensitivity to standard antibiotics. The main objective was to investigate genetic changes associated with antibiotic resistance in S. pneumoniae.ResultsOur results showed that resistant isolates contain a higher number of non-synonymous single nucleotide polymorphisms (SNPs) as compared to susceptible isolates. We were able to identify SNPs that alter a single amino acid in many genes involved in virulence and capsular polysaccharide synthesis. In addition, 90 SNPs were only presented in the resistant isolates, and 31 SNPs were unique and had not been previously reported, suggesting that these unique SNPs could play a key role in altering the level of resistance to different antibiotics.ConclusionWhole genome sequencing is a powerful tool for comparing the full genome of multiple isolates, especially those closely related, and for analysing the variations found within antibiotic resistance genes that lead to differences in antibiotic sensitivity. We were able to identify specific mutations within virulence genes related to resistant isolates. These findings could provide insights into understanding the role of single nucleotide mutants in conferring drug resistance.
Highlights
Streptococcus pneumoniae or pneumococcus is a leading cause of morbidity and mortality worldwide, in relation to community-acquired pneumonia
We report the whole genome sequencing for 10 pneumococcal isolates with a range of susceptibility and resistance to different antimicrobial drugs to elucidate the association between antibiotic resistance and the underlying genetic changes
The high degree of sequence conservation and the presence of the same single nucleotide polymorphisms (SNPs) especially those related to genes involved in β-lactam resistance in both sensitive and resistant isolates, makes it a difficult task to identify distinct mechanisms of resistance that differentiate strains with different drug-sensitivities, and that antibiotic resistance cannot be only linked to the presence of certain genes
Summary
Streptococcus pneumoniae or pneumococcus is a leading cause of morbidity and mortality worldwide, in relation to community-acquired pneumonia. According to the World Health Organization (WHO), this bacterium is responsible for 1.6 million deaths annually, including 0.7–1 million in children less than 5 years old and mostly in developing countries [4, 5]. In the United States, the annual number of deaths caused by pneumococcal pneumonia or meningitis is 40,000 [6, 7]. In Asia, S. pneumoniae is the major cause of acute respiratory infections (ARIs) in children under 5 years old [8]. Five of the 10 countries with the largest number of deaths caused by pneumococcal infections in children below 5 years old are located in Asia, including India, Jindal et al Journal of Biomedical Science (2018) 25:15. More than 93 different S. pneumoniae serotypes have been identified based on the immunochemical differences in the capsular polysaccharides [9,10,11]
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