TY - JOUR

T1 - Staphylococcal Phages Adapt to New Hosts by Extensive Attachment Site Variability

AU - Leinweber, Helena

AU - Sieber, Raphael N.

AU - Larsen, Jesper

AU - Stegger, Marc

AU - Ingmer, Hanne

N1 - Publisher Copyright: © 2021 American Society for Microbiology. All rights reserved.

PY - 2021

Y1 - 2021

N2 - Bacterial pathogens commonly carry prophages that express virulence factors, and human strains of Staphylococcus aureus carry Sa3int phages, which promote immune evasion. Recently, however, these phages have been found in livestock-associated, methicillin-resistant S. aureus (LA-MRSA). This is surprising, as LA-MRSA strains contain a mutated primary bacterial integration site, which likely explains why the rare integration events that do occur mostly happen at alternative locations. Using deep sequencing, we show that after initial integration at secondary sites, Sa3int phages adapt through nucleotide changes in their attachment sequences to increase homology with alternative bacterial attachment sites. Importantly, this homology significantly enhances integrations in new rounds of infections. We propose that promiscuity of the phageencoded tyrosine recombinase is responsible for establishment of Sa3int phages in LAMRSA. Our results demonstrate that phages can adopt extensive population heterogeneity, leading to establishment in strains lacking bona fide integration sites. Ultimately, their presence may increase virulence and zoonotic potential of pathogens with major implications for human health.

AB - Bacterial pathogens commonly carry prophages that express virulence factors, and human strains of Staphylococcus aureus carry Sa3int phages, which promote immune evasion. Recently, however, these phages have been found in livestock-associated, methicillin-resistant S. aureus (LA-MRSA). This is surprising, as LA-MRSA strains contain a mutated primary bacterial integration site, which likely explains why the rare integration events that do occur mostly happen at alternative locations. Using deep sequencing, we show that after initial integration at secondary sites, Sa3int phages adapt through nucleotide changes in their attachment sequences to increase homology with alternative bacterial attachment sites. Importantly, this homology significantly enhances integrations in new rounds of infections. We propose that promiscuity of the phageencoded tyrosine recombinase is responsible for establishment of Sa3int phages in LAMRSA. Our results demonstrate that phages can adopt extensive population heterogeneity, leading to establishment in strains lacking bona fide integration sites. Ultimately, their presence may increase virulence and zoonotic potential of pathogens with major implications for human health.

KW - AttP

KW - CC398

KW - Excision

KW - F 13

KW - Integrase

KW - Integration

KW - Livestock MRSA

KW - Phage

KW - Prophage

KW - Recombinase

KW - S. aureus

KW - Sa3int

U2 - 10.1128/mBio.02259-21

DO - 10.1128/mBio.02259-21

M3 - Journal article

C2 - 34872344

AN - SCOPUS:85121984752

VL - 12

JO - mBio

JF - mBio

SN - 2161-2129

IS - 6

M1 - e02259-21

ER -