Researchers at the University of Edinburgh have shown that Listeria responds to an antibiotic, despite the pathogen carrying genes that should make it highly resistant.
Their study report, published in the journal PLOS Genetics, reports that the susceptibility of the bacterium Listeria monocytogenes to the antibiotic is complex and involves interactions between resistance and virulence genes and the environment.
Early lab tests indicated that the antibiotic fosftomycin could not kill Listeria because the bacteria carries a gene that enables it to break down the drug. However, further studies found the drug was effective at killing Listeria in infected cells in the lab and in mice.
Researchers said the antibiotic should be reconsidered as a treatment for life-threatening Listeria infections.
“Our study focused on Listeria, but this important discovery may be relevant for other species of bacteria too. It is encouraging that we may be able to repurpose existing drugs in the race against antibiotic resistance,” said professor Jose Vazquez-Boland of the division of Infection Medicine and The Roslin Institute, University of Edinburgh.
Listeria infection, known as listeriosis, is a foodborne disease caused by eating contaminated beverages or foods, which include soft cheeses, smoked fish, pates, meats, salads, fresh and frozen produce, and other frozen foods such as ice cream. The study was funded by the Wellcome Trust and by Biotechnology and Biological Sciences Research Council (BBSRC) funding from the Roslin Institute Strategic Programme.
Researchers from the university in Scotland said genes that are only activated when the bacteria infect the body cancel out the effects of the drug-destroying gene.
“We found that a FosX (fosftomycin) enzyme encoded in the Listerial core genome confers intrinsic fosfomycin resistance to both pathogenic and non-pathogenic Listeria spp,” they said.
“However, in the genomic context of the pathogenic Listeria monocytogenes, FosX-mediated resistance is epistatically suppressed by two members of the PrfA virulence regulon, hpt and prfA, which upon activation by host signals induce increased fosfomycin influx into the bacterial cell.”
A group led by Professor Vazquez-Boland had previously shown that fosfomycin can treat Listeria in the body, despite it being ineffective in laboratory conditions. Because it was not effective in the lab, it was not considered for treatment of listeriosis.
The currently recommended treatment for listeriosis usually consists of a prolonged course of amoxicillin or ampicillin at high doses, often in combination with gentamicin.
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