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Roizman, D.

Publications and source records attributed to Roizman, D..

2 recordsLinked to original sources

Cross-linked agarose-gelatine beads as a substrate for investigating biofilms of bacterial pathogens

Treating chronic bacterial infections is challenging due to the formation of biofilms, making bacteria less susceptible to antimicrobials. In vitro models have limitations in replicating biofilm physiology. To address this problem, we have created a hydrogel substrate that combines crosslinked agarose and gelatine presented as beads, providing stability and resistance to autoclaving. Bacterial pathogens rapidly colonise these biogel beads when submerged in liquid culture. The substrate was tested with Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, showing more robust biofilm growth than its glass bead counterpart. Additionally, this led to increased virulence factor production and served as a reservoir for biofilm quorum sensing molecules. These features closely resemble clinical situations, suggesting a more accurate representation of biofilm-associated infections than current approaches. This new substrate offers a practical and convenient model for studying biofilms of bacterial pathogens, providing an efficient solution to the research community and holding promise for future breakthroughs.

microbiology↗

Antibiotic-induced recombination in Gram-negative bacteria requires the formation of double-strand breaks

Recombination is an essential process in bacterial drug resistance evolution. Fluoroquinolones, an important class of antibiotics, are known to stimulate recombination in Escherichia coli. When bacteria are exposed to antibiotics other than fluoroquinolones, including strong up-regulators of recombination pathways, there is no detectable change in the recombination level. Here we explore why fluoroquinolones, but not other antimicrobials, increase recombination rates. Fluoroquinolones, in contrast to other antibiotics, generate DNA double-strand breaks (DSBs). We tested whether other drugs that also cause double-strand breaks, such as mitomycin C and bleomycin, also affect bacterial recombination rates with consistent increases in recombination. A positive correlation between the number of DSBs and the recombination frequency was found. The manipulation of the level of DSBs directly impacted the recombination frequency. Our results highlight that only antibiotics that induce DNA double-strand breaks are more probable to increase genetic diversity via recombination. The stimulation of recombination by DSB-causing antimicrobials is an additional factor leading to the risk of antibiotic resistance evolution.

microbiology↗