Effect of clinically relevant antibiotics on bacterial extracellular vesicle release from Escherichia coli

Abstract

Sepsis, a leading cause of death in hospitals, can be defined as a dysregulated host inflammatory response to infection, which can lead to tissue damage, organ failure and cardiovascular complications. Although there is no cure for sepsis, the condition is typically managed with broad-spectrum antibiotics to eliminate any potential bacterial source of infection. However, a potential side effect of antibiotic treatment is the enhanced release of bacterial extracellular vesicles (BEVs), membrane-bound nanoparticles containing proteins and other biological molecules from their parent bacterium. Some of the Gram-negative extracellular vesicle (EV) cargo, including peptidoglycan associated lipoprotein and outer membrane protein A, have been shown to induce both acute and chronic inflammation in host tissue. It was hypothesized that the antibiotic concentration and mechanism of action may affect the amount of released BEVs, which could potentially exacerbate the host inflammatory response. This study evaluated nine clinically relevant antibiotics for their effect on EV release from Escherichia coli. Several beta-lactam antibiotics caused significantly more EV release, while quinolone and aminoglycoside antibiotics caused less vesiculation. Further study is warranted to corroborate the correlation between an antibiotic's mechanism of action and its effect on EV release, but these results underline the importance of antibiotic choice when treating patients with sepsis.

Keywords: Aminoglycoside; Antibiotics; Bacterial pathogenesis; Beta-lactam; Extracellular vesicles; Gram-negative bacteria; Outer membrane protein A; Peptidoglycan associated lipoprotein; Quinolone; Sepsis.