Abstract
Prophages play important roles in the transduction of various functional traits, including virulence factors, but remain debatable in harboring and transmitting antimicrobial resistance genes (ARGs). Herein we characterize a prevalent family of prophages in Streptococcus, designated SMphages, which harbor twenty-five ARGs that collectively confer resistance to ten antimicrobial classes, including vanG-type vancomycin resistance locus and oxazolidinone resistance gene optrA. SMphages integrate into four chromosome attachment sites by utilizing three types of integration modules and undergo excision in response to phage induction. Moreover, we characterize four subtypes of Alp-related surface proteins within SMphages, the lethal effects of which are extensively validated in cell and animal models. SMphages transfer via high-frequency conjugation that is facilitated by integrative and conjugative elements from either donors or recipients. Our findings explain the widespread of SMphages and the rapid dissemination of ARGs observed in members of the Streptococcus genus.
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Acknowledgements
This work was supported by the National Key R&D Program of China (2022YFD1800400), the National Natural Science Foundation of China (32172917, 32072915 and 31872517), the Natural Science Foundation of Jiangsu Province (BK20170710 and BK20210402), the Jiangsu Agriculture Science and Technology Innovation Fund (CX(22)3039), the Jiangsu Distinguished Professor Program (060804097), the Distinguished Young Scholars of the National Natural Science Foundation of China (Overseas), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The bioinformatics analyses were supported by the high-performance computing platform of Bioinformatics Center, Nanjing Agricultural University, and a startup award at Nanjing Agricultural University 060804009).
We would like to thank Dr. Zongfu Wu and Jiale Ma from Nanjing Agricultural University for their assistance in the bacterial virulence study, and Dr. Qijing Zhang from Iowa State University for fruitful discussions and manuscript improvement.
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JH and LW conceived and designed the experiments. JH, ZW, JL, YT, WZ and XH performed bioinformatics analyses. JH, XD, JS, PH and JZ generated strains and plasmids and performed HGT and other experiments. XD, GL and XW performed the cell and animal experiments. JH, XD and ZW wrote the original draft. LW, JL, DRC, YW and SM reviewed and edited the manuscript.
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Animal experiments were carried out at the Laboratory Animal Center of Nanjing Agricultural University, according to the guidelines of Experimental Animal Management Measures of Jiangsu Province and were approved by the Laboratory Animal Monitoring Committee of Jiangsu Province, China [Permit number: SYXK (Su) 2017-0007].
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Huang, J., Dai, X., Wu, Z. et al. Conjugative transfer of streptococcal prophages harboring antibiotic resistance and virulence genes. ISME J 17, 1467–1481 (2023). https://doi.org/10.1038/s41396-023-01463-4
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DOI: https://doi.org/10.1038/s41396-023-01463-4