The Integrative Conjugative Element ICESpyM92 Contributes to Pathogenicity of Emergent Antimicrobial-Resistant emm92...

Area of Science:

• Microbiology
• Genetics
• Infectious Diseases

Background:

• Antimicrobial resistance-encoding mobile genetic elements (MGEs) can increase bacterial pathogen virulence.
• Group A Streptococcus (GAS) from invasive infections shows increasing antimicrobial resistance (AMR).
• A specific 65-kb MGE, ICESpyM92, is conserved in emergent invasive emm92 GAS strains.

Purpose of the Study:

• To investigate if the ICESpyM92 MGE contributes to the disease potential of emergent emm92 GAS.
• To determine the role of ICESpyM92 and differential gene expression (DGE) in GAS invasive phenotypes.

Main Methods:

• Generated isogenic ICESpyM92 mutants in different emm92 GAS genomic backgrounds.
• Assessed GAS virulence using a mouse subcutaneous infection model.
• Measured in vitro and ex vivo DGE to understand ICESpyM92's impact on global gene expression.

Main Results:

• The presence of ICESpyM92 significantly enhanced GAS virulence in the mouse model.
• ICESpyM92 influenced GAS global gene expression in a manner dependent on the bacterial genomic background.
• MGE-associated DGE was linked to enhanced pathogenicity.

Conclusions:

• A combination of ICESpyM92 and core genome-dependent DGE contributes to invasive disease phenotypes in emergent emm92 GAS.
• This study demonstrates a link between AMR-encoding MGEs and bacterial pathogenicity through MGE-mediated DGE.
• Investigating the association between AMR-encoding MGEs and pathogenicity is crucial for understanding bacterial disease potential.