Unlocking Bacterial Hibernation: A New Frontier in Antibiotic Discovery

Researchers earlier this month may have scratched the surface of another weapon in the superbug arsenal of resistance mechanisms.

Drug-resistant superbugs are a major problem in hospitals where immunocompromised individuals are often the target of opportunistic pathogens like Enterococcus faecium. Efforts to curb their transmission have relied on the use of alcohol-based disinfectants but now researchers from Melbourne, Australia have uncovered alcohol-tolerant E. faecium strains, isolated from two hospitals in Australia.

A collection of 139 E. faecium strains collected over almost 19 years from two Australian hospitals showed a temporal increase in isopropanol resistance, the active ingredient in alcohol based hand rubs. More specifically strains collected after 2010 showed a 10-fold greater resistance to bacterial killing by isopropanol compared to strains collected before 2010. A population analysis of the collection using single nucleotide polymorphism-based phylogeny uncovered clonal groups that emerged in the hospitals over time exhibiting increasing alcohol tolerance. ST796, the most recent clonal group isolated in 2012, showed the highest isopropanol tolerance, and also exhibited cross-resistance to ethanol.

The authors show these alcohol tolerant strains had greater transmission from “disinfected” abiotic surfaces to the guts of mice. Strains of E. faecium were coated in mice cages followed by a standardized cleaning protocol using 70% isopropanol. After mice were exposed to the cleaned surfaces, colonization was allowed to occur for 7 days. A significantly greater number of mice were colonized by alcohol tolerant strains compared to susceptible strains. This revealed how alcohol cleaned surfaces could still contain enough CFU for colonization, and additionally that transmission and colonization of an animal could be achieved by alcohol tolerant bacteria, despite a standard disinfection procedure.

Efforts by the authors to identify a genetic link to alcohol tolerance led to whole genome sequencing. In their study mutations were found in the rpoB gene as well as a putative galactoside symporter and a putative phage region. Additionally, insertion elements were found upstream of a prophage region and on an endogenous plasmid containing a cell wall protein and two carbohydrate phosphotransferase proteins. The role of these proteins in alcohol tolerance remains to be determined but complementation of the galactoside symporter mutation and plasmid mutations significantly reduced doubling time in presence of isopropanol (doubling times of complimented strains were similar to wild type growth levels).

In Australia following deployment of alcohol-based hand rubs studies by the same group showed a decline in rates of hospital acquired MRSA and Gram-negative infections. Follow up studies by the Australian National Hand Hygiene program showed high compliance rates in health care facilities, >80% across the country. However, this study reveals a coinciding increase in the number of E. faecium tolerant isolates. Around the world alcohol-based disinfectants are pivotal to many hand hygiene programs in health care facilities. It will be important for future studies to be carried out globally especially in North America where hand hygiene programs have been well developed for many years. These studies will help to clearly define if this is a trend that is emerging globally. 

“Increasing tolerance of hospital Enterococcus faecium to hand-wash alcohols”

Science Translational Medicine 01 Aug 2018:

Vol. 10, Issue 452, eaar6115

DOI: 10.1126/scitranslmed.aar6115

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