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.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1898455 Studentship BB/M01116X/1 02/10/2017 30/09/2021 Ilyas Alav
 
Description Society Conference Grant
Amount £240 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 04/2020 
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