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. 2025 Jun 9;25(1):363.
doi: 10.1186/s12866-025-04066-5.

Impact of respiratory syncytial virus on Streptococcus pneumoniae resistance to β-lactam antibiotics: an investigative study in children

Lu Li  1 , Yushun Wan  2   3 , Yuncheng Wang  4 , Ye Tao  5 , Xiao Long  1 , Enmei Liu  6   7 , Yu Deng  8   9
Affiliations

Impact of respiratory syncytial virus on Streptococcus pneumoniae resistance to β-lactam antibiotics: an investigative study in children

Lu Li et al. BMC Microbiol. .

Abstract

Background: This study characterizes the molecular interplay between respiratory syncytial virus (RSV) glycoproteins (G/F) and Streptococcus pneumoniae (S.pn) penicillin-binding proteins (PBPs), while evaluating RSV's potential role in modulating S.pn β-lactam resistance.

Methods: Protein docking and pull-down assays assessed G/F-PBP interactions. In vitro RSV-S.pn co-culture experiments evaluated β-lactam susceptibility (MIC determination). We retrospectively analyzed 2012-2021 antimicrobial resistance data from 1-59-month-old community-acquired pneumonia patients at Chongqing Medical University Children's Hospital with confirmed S.pn and/or RSV nasopharyngeal carriage.

Results: Computational modeling revealed low G/F-PBP binding affinity (iPTM < 0.6), corroborated by absent PBP1a interaction in pull-down assays. RSV exposure did not alter S.pn β-lactam MICs (penicillin/amoxicillin ≤ 2 µg/mL; cefepime/cefotaxime ≤ 1 µg/mL; meropenem ≤ 0.25 µg/mL). Retrospective data showed elevated penicillin resistance in RSV + S.pn co-detections vs. S.pn alone during 2012 (2.8% vs. 40.9%), 2017 (2.8% vs. 30.4%), and 2018 (6.2% vs. 38.6%) (all p < 0.001). No RSV-associated resistance increases occurred for amoxicillin, cephalosporins, or meropenem.

Conclusions: RSV demonstrates negligible impact on S.pn β-lactam resistance mechanisms, elevated resistance rates to amoxicillin and cephalosporins necessitate enhanced antimicrobial stewardship through diagnostic-guided prescribing and resistance surveillance to optimize β-lactam efficacy in pediatric care.

Keywords: Streptococcus pneumoniae; Antibiotic resistance; Glycoprotein; Penicillin-binding protein; Respiratory syncytial virus.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All procedures of this study involving humans (individuals, medical records, human samples, and clinical isolates) were reviewed and approved by the Ethics Committee of Children’s Hospital affiliated to Chongqing Medical University(File No. 2023 − 492). All methods were performed in accordance with the relevant guidelines and regulations. Due to the retrospective nature of the study, the Ethics Committee of Children’s Hospital affiliated to Chongqing Medical University waived the need of obtaining informed consent. Clinical trial number: not applicable. This study adhered to the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Protein structure prediction and molecular docking. A RBD + ACE2. B G protein + PBP1a. C F proten + PBP1a
Fig. 2
Fig. 2
Pull-down assay of G/F proteins with PBP1a protein. A. PBP1a protein-bead incubation. Western blotting of Ni-beads co-incubated with purified pneumococcal PBP1a protein(≈ 80 kDa). B. Western blotting of G protein(≈ 130 kDa) in cell culture supernatant from 293T cells transfected with G plasmid. C. Western blotting of F protein(≈ 50 kDa) in the total cellular protein extract from 293T cells transfected with the F plasmid. D. Pull-down assay of PBP1a protein-bead co-incubated with G protein. Western blotting of PBP1a-bead(≈ 80 kDa) co-incubated with G protein(≈ 130 kDa) in 293T cell supernatant. E. Pull-down assay of PBP1a protein-bead with F protein. Western blotting of PBP1a-bead(≈ 80 kDa) co-incubated with F protein(≈ 50 kDa) in the total cellular protein extract from 293T cells. All experiments were performed with three biological replicates
Fig. 3
Fig. 3
Changes in the resistance rate of S.pn clinical isolates to β-lactam antibiotics from 2012 to 2021
Fig. 4
Fig. 4
Comparison of resistance rates to β-lactam antibiotics between RSV + S.pn and S.pn clinical isolates from 2012 to 2021. A. Penicillin resistance rates between RSV + S.pn and S.pn. B. Amoxicillin resistance rates between RSV + S.pn and S.pn. C. Cefotaxime resistance rates between RSV + S.pn and S.pn. D. Cefepime resistance rates between RSV + S.pn and S.pn. E. Meropenem resistance rates between RSV + S.pn and S.pn. ns, no significance; * p < 0.05, ** p < 0.01, *** p < 0.005, ****p < 0.001
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