Today, many disease-causing bacteria acquire resistance genes, which make antibiotic treatment ineffective. Especially, one gene, CTX-M-15, encoding an extended spectrum beta-lactamase (ESBL) can lead to resistance in E. coli causing urinary tract infections.
The team of researchers have shown that a cocktail of two common antibiotics, mecillinam and cefotaxime, can make these specific multi-resistant E. coli (extended spectrum beta-lactamase, ESBL) sensitive to treatment again.
The development of resistance towards either mecillinam or cefotaxime leads to concurrent sensitivity to the other drug - a phenomenon called collateral sensitivity. The study has been published in Nature Communications.
The CTX-M-15 gene is widely distributed globally and limits doctors' ability to effectively treat urinary tract infections.
"We need to take precautionary measures to avoid resistance, because it is very likely that this mutation will occur at some point. By giving both mecillinam and cefotaxime at the same time, the CTX-M-15 mutation works like a switch, and the bacteria become sensitive to treatment again," says first-author.
Another advantage using mecillinam and cefotaxime as a drug combination is that both drugs can be administered orally - as pills. Thereby doctors could use these two already approved drugs to treat multi-drug resistant E. coli (ESBL) infections.
An estimated 50 percent of women report having had urinary tract infection at some point in their lives, according to WHO. Thus, this new finding could be very relevant in treating this infection. Moreover, new antibiotics are fairly rare on the market, which forces doctors to find new uses of existing drugs.
The switch only works with this specific strain of ESBL E. coli. Hence, it is crucial to know the profile of the disease-causing bacteria in order to choose the right combination strategy.
"This could make it possible to sequence samples from patients in the clinic and tailor the antibiotic treatment based on the mutational landscape in the test," says the senior author.
In this new study, the researchers used adaptive laboratory evolution combined with a random mutagenesis approach to find E. coli mutants resistant to mecillinam and cefotaxime. Using this method, they could mimic the natural evolutionary process in the lab. The team looked at the CTX-M-15 beta-lactamase gene, which is highly transferable in nature and thus has a high risk of spreading between disease-causing bacteria.
The results showed that bacteria, which had become resistant to mecillinam, were now sensitive to the drug cefotaxime. At the same time, bacteria that had become resistant to cefotaxime were now sensitive towards mecillinam.
"The results are interesting because we showed that bacteria simply can't survive both drugs. Also, the same gene with only one mutation shows this switch-function. Normally, you will find multiple mutations in multiple resistance genes, controlling different mechanisms," author says.
Thus, this proof-of-concept method will allow others to study other resistance genes to find new drug combinations with collateral sensitivity. This will hopefully prolong the fast development of antibiotic resistance seen today.
http://www.biosustain.dtu.dk/nyhedsbase/nyhed?id=06D4F29B-F7AA-41D1-9D69-D331EC57B341
https://www.nature.com/articles/s41467-019-08529-y
Cocktail of common antibiotics can fight resistant E. coli
- 1,220 views
- Added
Edited
Latest News
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Mapping microbiome in metas…
By newseditor
Posted 22 Apr
Other Top Stories
Liver damage mechanism in malaria
Read more
Targeting gut microbes for treating atherosclerosis?
Read more
Bacteria battle: How one changes appearance, moves away to resist t…
Read more
Mechanism of viral activation following neural stress
Read more
'Mykrobe Predictor' software for quick and accurate prediction of a…
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Neuronal activity rapidly r…
By newseditor
Posted 22 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar