rRNA Operon Copy Number Can Explain the Distinct Epidemiology of Hospital-Associated Methicillin-Resistant...

Area of Science:

• Microbiology
• Molecular Biology
• Epidemiology

Background:

• The differing spread of hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) and community-associated MRSA (CA-MRSA) is not well understood.
• Staphylococcus aureus possesses either five or six rRNA operon copies.

Purpose of the Study:

• To investigate the role of rRNA operon copy number in the adaptation and epidemiology of MRSA strains.
• To determine the impact of antibiotic pressure on rRNA operon copy number and bacterial fitness.

Main Methods:

• Comparative analysis of rRNA operon copy numbers in HA-MRSA, CA-MRSA, methicillin-susceptible S. aureus (MSSA), and MSSA from cystic fibrosis patients.
• In vitro experiments to assess the effect of antibiotic pressure on rRNA operon copy loss.
• Correlation analysis between rRNA copy number, resistance profiles, and bacterial fitness.

Main Results:

• A significantly higher proportion of HA-MRSA (67.5%) and cystic fibrosis MSSA (32.4%) isolates had five rRNA operon copies compared to CA-MRSA (23.2%) and general MSSA (7.7%) isolates.
• Antibiotic pressure in vitro induced rRNA operon copy loss.
• Isolates with six rRNA copies demonstrated greater fitness than those with five copies in the absence of antibiotic pressure.

Conclusions:

• HA-MRSA and cystic fibrosis-associated S. aureus likely adapted to high antibiotic environments through rRNA operon loss, facilitating resistance.
• This adaptation, however, reduced strain fitness, explaining their limited community success.
• CA-MRSA, retaining six rRNA operons, exhibited higher fitness, enabling community survival and spread.