RT Journal Article SR Electronic T1 A tale of two plasmids: contributions of plasmid associated phenotypes to epidemiological success among Shigella JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.12.17.473221 DO 10.1101/2021.12.17.473221 A1 P. Malaka De Silva A1 George E. Stenhouse A1 Grace A. Blackwell A1 Rebecca J. Bengtsson A1 Claire Jenkins A1 James P.J. Hall A1 Kate S. Baker YR 2021 UL http://biorxiv.org/content/early/2021/12/18/2021.12.17.473221.abstract AB Dissemination of antimicrobial resistance (AMR) genes by horizontal gene transfer (HGT) mediated through plasmids is a major global concern. Genomic epidemiology studies have shown varying success of different AMR plasmids during outbreaks, but the underlying reasons for these differences are unclear. Here, we investigated two Shigella plasmids (pKSR100 and pAPR100) that circulated in the same transmission network but had starkly contrasting epidemiological outcomes to identify plasmid features that may have contributed to the differences. We used plasmid comparative genomics to reveal divergence between the two plasmids in genes encoding AMR, SOS response alleviation, and conjugation. Experimental analyses revealed that these genomic differences corresponded with reduced conjugation rates for the epidemiologically successful pKSR100, but more extensive AMR, reduced fitness costs, and a reduced SOS response in the presence of antimicrobials, compared with the less successful pAPR100. The discrepant phenotypes between the two plasmids are consistent with the hypothesis that plasmid associated phenotypes contribute to determining the epidemiological outcome of AMR HGT and suggest that phenotypes relevant in responding to antimicrobial pressure and fitness impact may be more important than those around conjugation in this setting. Plasmid phenotypes could thus be valuable tools in conjunction with genomic epidemiology for predicting AMR dissemination.Competing Interest StatementThe authors have declared no competing interest.