biostudies-literatureZhao JFundamental Research Funds for the Central UniversitiesPriority Academic Program Development of Jiangsu Higher Education InstitutionsNational Natural Science Foundation of ChinaNatural Science Foundation of Ningxia Hui Autonomous Region540https://www.ebi.ac.uk/biostudies/studies/S-EPMC12462003biostudies-literatureUnknown21(1)<h4>Background</h4>The global spread of multidrug-resistant (MDR) bacteria prompts the exploration of innovative antimicrobial strategies. Phage lysins-peptidoglycan hydrolases known for species-specific activity and low resistance potential-offer promising alternatives to conventional antibiotics. However, their typically narrow spectrum limits broad therapeutic application. To overcome this limitation, we leveraged the wide distribution of streptococcal mobilizable prophage (SMphage) families across Streptococcus species as a strategy to discover lysins with inherent broad-spectrum potential. Within these conserved prophages, we expressed PlyNJ3, an SMphage-derived endolysin homolog identified in S. suis, and evaluated its therapeutic efficacy in infection models.<h4>Results</h4>PlyNJ3 eBMC veterinary researchPlyNJ3: a three-domain endolysin with broad-spectrum anti-streptococcal activity and synergistic efficacy against multidrug-resistant Streptococcus suis.PMC12462003PAPDKYCXJC202500132172917No. 2024AAC05098Han PGu SJi HHuang JYin CWang XZhao JWang JWang LfalsePlyNJ3: a three-domain endolysin with broad-spectrum anti-streptococcal activity and synergistic efficacy against multidrug-resistant Streptococcus suis.<h4>Background</h4>The global spread of multidrug-resistant (MDR) bacteria prompts the exploration of innovative antimicrobial strategies. Phage lysins-peptidoglycan hydrolases known for species-specific activity and low resistance potential-offer promising alternatives to conventional antibiotics. However, their typically narrow spectrum limits broad therapeutic application. To overcome this limitation, we leveraged the wide distribution of streptococcal mobilizable prophage (SMphage) families across Streptococcus species as a strategy to discover lysins with inherent broad-spectrum potential. Within these conserved prophages, we expressed PlyNJ3, an SMphage-derived endolysin homolog identified in S. suis, and evaluated its therapeutic efficacy in infection models.<h4>Results</h4>PlyNJ3 e2025-01-01T00:00:00Z2025 Sep2026-05-01T03:22:19.299Z2026-05-01T03:11:07.456ZS-EPMC124620034099369810.1186/s12917-025-04975-7