# In Silico Identification and Characterization of Drug Targets in Streptococcus pneumoniae ATCC 700669 (Serotype 23F) by Subtractive Genomics

**Authors:** Tolossa Duguma, Hunduma Dinka

PMC · DOI: 10.1155/2024/5917667 · BioMed Research International · 2024-01-20

## TL;DR

This study identifies four potential drug targets in a specific strain of Streptococcus pneumoniae using bioinformatics to combat antibiotic resistance.

## Contribution

The novel contribution is the in silico identification of four nonhomologous, essential proteins in S. pneumoniae serotype 23F as potential drug targets.

## Key findings

- S. pneumoniae serotype 23F has 23 unique metabolic pathways not shared with humans.
- Four proteins were identified as potential drug targets based on essentiality and nonhomology with human proteins.
- The prioritized proteins are UDP-N-acetylglucosamine 1-carboxyvinyltransferase, UDP-N-acetyl muramate dehydrogenase, D-alanine-D-alanine ligase, and alanine racemase.

## Abstract

Streptococcus pneumoniae (S. pneumoniae) is an important pathogen worldwide that causes pneumococcal infections which are related to high rates of morbidity and mortality especially in young children, older adults, and immune-compromised persons. Antibiotic resistance in S. pneumoniae is a serious problem across the world from time to time, resulting in treatment failure and diminished value of older medicines. Therefore, the objective of this study was to identify new putative drug targets against S. pneumoniae serotype 23F by using subtractive genomics. By using bioinformatics tools such as NCBI, UniProt KB, PDB, KEGG, DEG, PSORTb, CD hit, DrugBank database, and other softwares, proteins involved in unique metabolic pathways of S. pneumoniae serotype 23F were studied. The result indicates that this serotype consists of 97 metabolic pathways of which 74 are common with that of human, and 23 pathways are unique to the serotype 23F. After investigation and analysis of essentiality, nonhomology, subcellular localization, having drug targets, and enzymatic activity, four proteins were prioritized as druggable targets. These druggable proteins include UDP-N-acetylglucosamine 1-carboxyvinyltransferase, UDP-N-acetyl muramate dehydrogenase, D-alanine-D-alanine ligase, and alanine racemase that are found in S. pneumoniae serotype 23F. All these four proteins are essential, are nonhomologous with human proteins, have drug targets, and are located in cell cytoplasm. Therefore, the authors recommend these proteins to be used for efficient drug design against S. pneumoniae serotype 23F after experimental validation for essentiality and druggability.

## Linked entities

- **Species:** Streptococcus pneumoniae (taxon 1313), Streptococcus pneumoniae ATCC 700669 (taxon 561276)

## Full-text entities

- **Diseases:** pericarditis (MESH:D010493), invasive disease (MESH:D009361), meningitis (MESH:D008580), Invasive pneumococcal disease (MESH:D011008), bronchitis (MESH:D001991), septic arthritis (MESH:D001170), osteomyelitis (MESH:D010019), infected (MESH:D007239), immuno-compromised (MESH:D000163), bacteraemia (MESH:C531821), urinary tract infections (MESH:D014552), bacterial meningitis (MESH:D016920), bacterial pneumonia (MESH:D018410), conjunctivitis (MESH:D003231), S. pneumoniae infections (MESH:D011014), sinusitis (MESH:D012852), cellulitis (MESH:D002481), sepsis (MESH:D018805), peritonitis (MESH:D010538), otitis media (MESH:D010033), death (MESH:D003643), brain abscess (MESH:D001922), endocarditis (MESH:D004696), Alanine (MESH:C536414), systemic infections (MESH:D012141)
- **Chemicals:** carbapenems (MESH:D015780), enolpyruvyl-UDP-N-acetylglucosamine (MESH:C038277), amino sugar (MESH:D000606), amino acids (MESH:D000596), fosfomycin (MESH:D005578), penicillin (MESH:D010406), macrolides (MESH:D018942), cephalosporin (MESH:D002511), vancomycin (MESH:D014640), lincosamides (MESH:D055231), propanoic acid (MESH:C029658), D-cycloserine (MESH:D003523), ATP (MESH:D000255), cloxacillin (MESH:D003023), FAD (MESH:D005182), (5Z)-3-(4-CHLOROPHENYL)-4-HYDROXY-5-(1-NAPHTHYLMETHYLENE) (-), L-alanine (MESH:D000409), NADPH (MESH:D009249), erythromycin (MESH:D004917), UDP-N-acetylmuramic acid (MESH:D014538), Beta-lactam (MESH:D047090), clindamycin (MESH:D002981), levofloxacin (MESH:D064704), 8-anilinonaphthalene-1-sulfonic acid (MESH:C515594), phosphoenolpyruvate (MESH:D010728), Pyridoxal phosphate (MESH:D011732), fluoroquinolones (MESH:D024841), UDP-N-acetylglucosamine (MESH:D014537)
- **Species:** Streptococcus pneumoniae D39 (strain) [taxon 373153], Streptococcus pneumoniae (species) [taxon 1313], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Homo sapiens (human, species) [taxon 9606], Streptococcus pneumoniae 23F (strain) [taxon 216600]

## Full text

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## Figures

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## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC10821801/full.md

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Source: https://tomesphere.com/paper/PMC10821801