Professor Aras Kadioglu

Professor of Bacterial Pathogenesis Clinical Infection, Microbiology & Immunology

Research

Research Overview

I head the Bacterial Pathogenesis and Immunity Group in the Institute of Infection & Global Health. My area of expertise is in host pathogen interactions, in particular cellular immunity to respiratory bacterial infections. My training is in bacteriology and immunology (infection immunology), and in vivo infection modeling. My research group uses these multifaceted approaches to investigate how pathogens such as Streptococcus pneumoniae, Streptococcus pyogenes, GBS, and Pseudomonas aeruginosa cause disease and interact with host cellular immunity, in particular in regulation of infection and inflammation. To this end, we have developed clinically relevant mouse models of respiratory and systemic infection to elucidate mechanistic understanding of the disease processes involved and the host immune responses to infection.

As part of these efforts, we also work on the development of novel anti-bacterial therapeutics such as phage therapy, bacterial toxin inhibitors, phagocyte activators and the development of new vaccines through the Liverpool Centre for Global Vaccine Research. My most recent publications in these fields have been in Nature Microbiology, Nature Biotechnology, Nature Communications, the AJRCCM and JACI amongst others. My research group currently consists of 8 PhD students, 4 postdocs and 2 Fellows. Our research is funded by MRC Programme and project grants, JPI-AMR funding, the Wellcome Trust, Meningitis Now, BBSRC, Innovate UK and most recently by the European Commission Horizon 2020 programme as well as by industrial partners including GSK and Roche.

Bacterial vaccines

My group works on developing new vaccines to pathogens such as the pneumococcus, GAS and GBS. We have recently developed (after 8 years of funded research) a novel and cost-effective protein-based vaccine against pneumococcal disease. This vaccine was developed by the reverse vaccinology approach, using genomics, computational analysis, antigen discovery/selection and in vitro and in vivo functional assays and protection/immunisation models. Our work has led to a tripartite pneumococcal vaccine that provides universal coverage through antibody and cell mediated immune responses. This vaccine is now being taken forward by ReNewVax Ltd, a University of Liverpool spin-out company co-founded by myself and my postdoctoral scientist (Dr. Marie Yang), now CSO of ReNewVax. The company was created through seed funding awarded by Innovate ICURe and funding from the University of Liverpool’s Enterprise Investment Fund. We anticipate Phase 1 immunogenicity, safety and tolerability results in adults by end of 2025. In my group, we have ongoing vaccine work on GAS and GBS taking the same reverse vaccinology approach.

AMR - novel alternatives to antibiotics

We have clinically relevant and reproducible in vivo disease models to test for new treatments against AMR infections. Importantly, our models can also be used for pre-clinical testing of drug dosing strategies coupled to monitoring for resistance development and elucidation of the factors which may drive it i.e. improved efficacy of drug delivery to maximise the dose to infected cells while minimising exposure and thereby the development of AMR. Finally, our models can also be used to test novel antimicrobials in combination with existing antibiotics in dual therapy strategies to minimise the risks of AMR development. The models we have are unique and offer significant added value to our understanding of the development and treatment of AMR.

We currently use our clinically relevant models to test for novel alternatives to antibiotics, such as P4 peptide immunotherapy, phage therapy and liposome toxin sequestration therapy. Our work on toxin sequestration for example, has recently been published in Nature Biotechnology, our work on Pseudomonas aeruginosa adaptation and persistence during chronic lung infection in Nature Communications and our work on phage therapy against chronic lung infections in Thorax.

Finally, our work in this area is funded by the MRC, JPI-AMR, Horizon 2020 and industrial collaborators such as GSK, Roche, Grifols, and Neem Biotech.

Research Group Membership

Research Grants

The evolutionary ecology of bacterial immune mechanisms

EUROPEAN COMMISSION

July 2021 - December 2022

Bench Fees - Fahad Mashwal

ROYAL EMBASSY OF SAUDI ARABIA CULTURAL BUREAU IN LONDON (UK)

July 2021 - September 2024

The impact of thermally-regulated cell wall modifications on Streptococcus pneumoniae pathogenesis

MEDICAL RESEARCH COUNCIL

July 2023 - July 2026

Noor Allehyani - Bench Fees

SHAQRA UNIVERSITY (SAUDI ARABIA)

June 2021 - September 2024

SPOR-COV: Prophylaxis of COVID-19 using Innate Immunity

INNOVATE UK (UK)

September 2020 - May 2022

Understanding host interactions with high consequence pathogens using super resolution light microscopy in biocontainment

BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL

August 2022 - July 2023

An evidence-based preclinical framework development antimicrobial therapeutics cystic fibrosis

CYSTIC FIBROSIS TRUST (UK)

October 2021 - September 2025

Does CRISPR-Cas imunity limit the efficacy of phage therapy

BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL

February 2021 - January 2024

Inhalable Aerosol Light Source for Controlling Drug-Resistant Bacterial Lung Infections - Light4Lungs

EUROPEAN COMMISSION

December 2019 - May 2024

Bench fees Hajar Ahmed AlQadeeb

ROYAL EMBASSY OF SAUDI ARABIA CULTURAL BUREAU IN LONDON (UK)

January 2018 - January 2021

EEID travel grant: Environmental determinants of pneumococcal transmission and evolution

BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL

September 2019 - October 2019

Bench Fees for Tarfah Abdulrahman A Alshuhaytan

ROYAL EMBASSY OF SAUDI ARABIA CULTURAL BUREAU IN LONDON (UK)

June 2019 - May 2023

The role of immune tolerance and regulation in pneumococcal carriage and invasive disease

MEDICAL RESEARCH COUNCIL

June 2017 - August 2023

Mechanisms for acquisition and transmission of successful antibiotic resistant pneumococcal clones pre- and post-vaccination

MEDICAL RESEARCH COUNCIL

July 2017 - September 2021

Identifying new members of virulence signalling networks: three new sensor kinases in the GacS network of Pseudomonas aeruginosa

MEDICAL RESEARCH COUNCIL

November 2015 - October 2018

Preclinical development and evaluation of a mucosal protein-based adjuvanted vaccine against pneumococcal meningitis and sepsis

MENINGITIS NOW (UK)

September 2016 - August 2019

Bench fees for SHAMSUL BAHRIN BIN GULAM ALI

MALAYSIAN GOVERNMENT (MALAYSIA)

January 2016 - June 2019

Biofilm Disruption: Proof of Concept Study.

HOFFMANN-LA ROCHE, F, LTD (SWITZERLAND)

July 2015 - April 2017

Bench fees for Alessandra Romero Ramirez

PRESIDENCIA DEL CONSEJO DE MINISTROS (PERU)

September 2016 - September 2020

Discovery of Pseudomonas aeruginosa mutations associated with chronic lung infection in children with CF.

ACTION MEDICAL RESEARCH (UK)

August 2017 - September 2021

2014 allocation - Wellcome ISSF non clinical fellowships

WELLCOME TRUST (UK)

May 2015 - October 2018

Development of a novel nasal therapy containing antimicrobial peptides to treat MRSA carriage

SISAF LTD (UK)

October 2016 - April 2018

Bench Fees (Hind Jaber Al Thagafi)

ROYAL EMBASSY OF SAUDI ARABIA, ROYAL EMBASSY OF SAUDI ARABIA CULTURAL BUREAU IN LONDON (UK)

October 2015 - September 2018

Personalising sepsis therapy in children through improved mechanistic understanding of phagocytic killing

ALDER HEY CHILDREN'S CHARITY (UK), ALDER HEY CHILDREN'S NHS FOUNDATION TRUST (UK)

September 2016 - March 2020

The Role Of The Blood-Brain Barrier During Pneumococcal Meningitis

THE TERESA ROSENBAUM GOLDEN CHARITABLE TRUST (THE ROSETREES TRUST) (UK)

January 2017 - December 2017

Commonwealth Scholarship UK: Bench Fees (Shadia)

COMMONWEALTH SCHOLARSHIP COMMISSION (UK)

March 2015 - February 2018

P4-IVIG immunotherapy for adjunct treatment of severe respiratory infection with sepsis.

MEDICAL RESEARCH COUNCIL

April 2015 - May 2017

Warwick Studentship

UNIVERSITY OF WARWICK (UK)

October 2013 - March 2017

Mansoor Alsahag - Bench fees

ROYAL EMBASSY OF SAUDI ARABIA

October 2014 - September 2015

Virulence adaptations within sequential cystic fibrosis isolates of Burkholderia cenocepacia

UNIVERSITY OF EXETER (UK)

July 2013 - December 2014

How do interactions between S. pneumoniae and NT H. influenzae influence upper respiratory tract carriage density and duration?

GLAXOSMITHKLINE BIOLOGICALS S.A. (BELGIUM)

April 2014 - August 2016

Hesham Malak Bench Fees

ROYAL EMBASSY OF SAUDI ARABIA

October 2012 - February 2015

Tackling superbugs by targeting their decision making networks during infection.

THE TERESA ROSENBAUM GOLDEN CHARITABLE TRUST (THE ROSETREES TRUST) (UK)

March 2014 - February 2015

Bridging and accelerating the translation of novel scientific findings for health and wealth gain

MEDICAL RESEARCH COUNCIL

March 2014 - August 2015

Understanding the epidemiology of life threatening invasive Group A Streptococcal infections in Merseyside.

LIVERPOOL HEALTH PARTNERS (UK)

March 2013 - April 2013

The fast track development of novel therapeutics and vaccine candidates against pneumococcal meningitis

MENINGITIS UK

July 2013 - December 2015

Zuliza Mohamed - bench fees

MINISTRY OF HEALTH MALAYSIA (MALAYSIA)

December 2014 - November 2017

Breno Salgado - bench fees

COORDENACAO DE APERFEICOAMENTO DE PESSOAL DE NIVEL SUPERIOR (CAPES) (BRAZIL)

August 2014 - September 2016

Candida-Bacteria Communication in Oral Biofilms

NATIONAL INSTITUTES OF HEALTH (USA)

July 2013 - July 2016

Reham Omar Hassan Yahya (Bench Fees)

ROYAL EMBASSY OF SAUDI ARABIA

October 2012 - January 2015

Research Collaborations

Dr. Dan Neill

External: University of Dundee

Pneumococcal immunity/virulence/genomics

Prof. Jo Fothergill

Internal

Pseudomonas aeruginosa, Phage therapy, AMR

Prof. Jim O'Gara

External: University of Galway

Staph. aureus pathogenesis, MRSA infections

Prof. Jay Hinton

Internal

Bacterial RNAseq

Prof. Neil French

Internal

Group A Streptococcus, Streptococcus pneumonaie, vaccine development

Prof. Stephen Gordon

External: LSTM

Streptococcus pneumoniae, experimental human challenge model, carriage

Dr. Steve Porter

External: University of Exeter

Pseudomonas aeruginosa signalling pathways

Dr. Martin Antonio

External: MRC Gambia

Streptococcus pneumoniae, vaccine development

Dr. Ed Lavelle

External: Trinity College Dublin

Novel vaccine development