Disruption of the cpsE and endA Genes Attenuates Streptococcus pneumoniae Virulence: Towards the Development of a Live Attenuated Vaccine Candidate
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Strain and Growth Conditions
2.2. Construction of cpsE::tetL and endA::aphA-3 Knockout Mutants
2.3. Transmission Electron Microscopy
2.4. In Vitro Studies
2.5. In Vivo Studies
3. Results
3.1. Disruption of the cpsE Gene Led to Loss of the Capsule in S. Pneumoniae
3.2. In Vitro Growth Characteristics
3.3. In Vitro Biofilm Formation
3.4. Density and Duration of Nasopharyngeal (NP) Colonisation in Mice
3.5. Effect of Immunisation with the Gene-Disrupted Mutant Strains on Local and Systemic Antibody Titres
3.6. Survival Analysis
3.7. Attenuation of Virulence
4. Discussion
4.1. Capsule Mutations Affected the Growth of S. Pneumoniae
4.2. Biofilm Profiles of the Candidate Vaccine Strains
4.3. Colonisation Potential of the Pneumococcal Gene-Knockout Strains
4.4. Antibody Response to Candidate Vaccine Strains
4.5. Immune Protection Conferred by Gene-Knockout Strains
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Strains | LD50 (CFU) | Fold of Attenuation * |
---|---|---|
SPEC | 3.5 × 1010 | 23 |
Wild-type D39 | 1.5 × 109 | 1 |
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Amonov, M.; Simbak, N.; Wan Hassan, W.M.R.; Ismail, S.; A. Rahman, N.I.; Clarke, S.C.; Yeo, C.C. Disruption of the cpsE and endA Genes Attenuates Streptococcus pneumoniae Virulence: Towards the Development of a Live Attenuated Vaccine Candidate. Vaccines 2020, 8, 187. https://doi.org/10.3390/vaccines8020187
Amonov M, Simbak N, Wan Hassan WMR, Ismail S, A. Rahman NI, Clarke SC, Yeo CC. Disruption of the cpsE and endA Genes Attenuates Streptococcus pneumoniae Virulence: Towards the Development of a Live Attenuated Vaccine Candidate. Vaccines. 2020; 8(2):187. https://doi.org/10.3390/vaccines8020187
Chicago/Turabian StyleAmonov, Malik, Nordin Simbak, Wan Mohd. Razin Wan Hassan, Salwani Ismail, Nor Iza A. Rahman, Stuart C. Clarke, and Chew Chieng Yeo. 2020. "Disruption of the cpsE and endA Genes Attenuates Streptococcus pneumoniae Virulence: Towards the Development of a Live Attenuated Vaccine Candidate" Vaccines 8, no. 2: 187. https://doi.org/10.3390/vaccines8020187