A tale of two plasmids: contributions of plasmid associated phenotypes to epidemiological success among Shigella

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 efficiencies 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.