Targeting Efflux Pumps to Combat Antimicrobial Resistance
Lead Research Organisation:
University of Birmingham
Department Name: Institute of Microbiology and Infection
Abstract
Antibiotic resistance is currently one of the gravest threats to global public health and economic development, estimated to cause an additional 10 million deaths per year and a loss of up to US$100 trillion from the global economy by 2050. Bacteria can become resistant to antibiotics in many ways but one important mechanism is through the action of multi-drug efflux pumps. These pumps are located in the bacterial cell membrane and function to pump antibiotics out of cells. This reduces intracellular concentration of drug within bacteria allowing them to survive at higher drug concentrations and therefore, conferring antibiotic resistance. Many efflux pumps can export multiple classes of antibiotic so the bacteria are resistant to many drugs at the same time, known as multi-drug resistance (MDR).
The resistance-nodulation-division (RND) family of efflux pumps confer antibiotic resistance to many human and animal pathogens, including the foodborne pathogen Salmonella. In Salmonella, the major efflux pump of this family, AcrB, confers antibiotic resistance and is commonly over-expressed in multi-drug resistant (MDR) clinical and veterinary isolates. RND pumps, including AcrB, are organized as tri-partite systems, consisting of an inner membrane efflux transporter, a periplasmic adaptor protein (PAP) and an outer membrane channel.
Previous studies have shown that PAPs are a good target for development of efflux inhibitors. If an appropriate inhibitor of PAPs was identified, it could be employed in tandem with an existing antibiotic to restore susceptibility to that antibiotic and prevent the recurrence of resistance. Therefore, this project will aim to develop/identify potential inhibitor molecules of the PAPs.
The resistance-nodulation-division (RND) family of efflux pumps confer antibiotic resistance to many human and animal pathogens, including the foodborne pathogen Salmonella. In Salmonella, the major efflux pump of this family, AcrB, confers antibiotic resistance and is commonly over-expressed in multi-drug resistant (MDR) clinical and veterinary isolates. RND pumps, including AcrB, are organized as tri-partite systems, consisting of an inner membrane efflux transporter, a periplasmic adaptor protein (PAP) and an outer membrane channel.
Previous studies have shown that PAPs are a good target for development of efflux inhibitors. If an appropriate inhibitor of PAPs was identified, it could be employed in tandem with an existing antibiotic to restore susceptibility to that antibiotic and prevent the recurrence of resistance. Therefore, this project will aim to develop/identify potential inhibitor molecules of the PAPs.
Organisations
People |
ORCID iD |
Jessica Blair (Primary Supervisor) | |
Ilyas Alav (Student) |
Publications
Colclough AL
(2020)
RND efflux pumps in Gram-negative bacteria; regulation, structure and role in antibiotic resistance.
in Future microbiology
Whittle EE
(2019)
Flow Cytometric Analysis of Efflux by Dye Accumulation.
in Frontiers in microbiology
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/M01116X/1 | 30/09/2015 | 31/03/2024 | |||
1898455 | Studentship | BB/M01116X/1 | 01/10/2017 | 24/03/2022 | Ilyas Alav |
Description | Society Conference Grant |
Amount | £240 (GBP) |
Organisation | Microbiology Society |
Sector | Learned Society |
Country | United Kingdom |
Start | 03/2020 |
End | 04/2020 |
Description | Helping out with the IMI Summer School |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | A group of A-level students from a local school were invited to the Institute of Microbiology and Infection for an open day. The students took part in small basic microbiology demonstrations and experiments to get a taste of practical experiments at university. |
Year(s) Of Engagement Activity | 2019 |
Description | Presentation at M4 2019 conference |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Attended the 2019 M4 Microbiology Conference at Nottingham, where I presented a research poster on my latest research. I had the opportunity to discuss my work with other researchers and receive feedback. |
Year(s) Of Engagement Activity | 2018,2019 |