Prof Jose Bengoechea (JB) PhD work in Spain focused on deciphering features of the outer membrane of Yersinia spp associated with virulence, leveraging biochemistry and biophysics approaches. This training was key for a successful postdoc under Prof Mikael Skurnik (University of Turku, Finland) where he provided novel mechanistic insights into the regulation of the Yersinia LPS O-polysaccharide biosynthesis, and the role of the LPS core in virulence. In 2002, Prof Bengoechea was awarded one of only fifty Spanish national biomedical research tenure-track positions, funded by the Spanish Ministry of Health, to set up his laboratory in a University Hospital (Son Dureta, Mallorca, Spain). He continued his research on Yersinia but focusing now on the lipid A, and he established a new research programme on Klebsiella pneumoniae pathogenesis. Despite the clinical relevance of this pathogen, it was understudied and most of the research was devoted to decipher the molecular basis of Klebsiella antibiotic resistance. While at Spain, JB took senior leadership positions as Director of Research of the Hospital (with more than 1000 hospital beds and 26 operating rooms), director of the Infection and Immunity programme of a new research centre on respiratory diseases funded by the Spanish and Balearic Islands governments, and as coordinator of the research programme on new therapeutics targets for infectious diseases (15 research groups across Spain) and member of the executive board of the Spanish national centre on respiratory diseases (more than 400 researchers). In 2007, JB secured the only tenure position in microbial pathogenesis offered that year at the Spanish Research Council. In 2013, he was recruited as Professor by Queen’s University Belfast (Northern Ireland) as strategic appointment to develop further the area of microbial pathogenesis within the School of Medicine. At Queen’s JB continued his research on K. pneumoniae infection biology, leveraging this knowledge platform to establish a host-directed therapeutics programme in collaboration with AstraZeneca. In 2016, he was appointed the founding director of the Wellcome-Wolfson Institute for Experimental Medicine; a £32M purpose build research centre housing 50 groups, basic and clinical, investigating respiratory disease, eye disease, and infectious diseases, and member of the Executive Board of the Faculty of Medicine, Health and Life Sciences (4 years) and of the School of Medicine, Dentistry, and Biomedical Sciences management board (7 years). In all this leadership positions, he has been responsible for research governance, budget control and allocation, responsible for multimillion pounds technology units, and to line manage academic, clerical and technical staff. In the role of Institute Director, JB set the vision, mission, and strategy for the Institute. The Institute focuses on eye disease, cardiovascular disease, respiratory disease and infectious diseases. Its standout performance, ranking 4th in the Biomedicine Unit of assessment in REF2021 from second the last in the previous REF, reflects JB's impact on the research culture, promoting health impact. Several quality indexes mark this success. In the last six years, WWIEM experienced a growth of 90% in research income reaching £52 M (a sustained annual income of £11 M with 27% increase in UKRI funding). The bespoke support to clinical studies resulted in a 40% increase in NIHR funding leading UK-wide clinical trials, and bridging clinical and basic researchers to apply successfully for MRC and NIHR EME funding. The Institute has increased significantly its collaborations with industrial stakeholders (£5M increase), and we have actively supported three spinouts (supported by Innovate UK and Invest NI). JB successfully led high-level alliances between universities and governmental stakeholders. This work is reflected by the development of a new £5 M pediatric cardiology academic unit (in 2023), funded by Northern Ireland Department of Health, between Queen’s University Belfast and Ulster University (three academic units). This academic unit has been done in partnership with the Republic of Ireland, resulting in a true transnational academic unit. He acted as external adviser (2021-2023) to the West African Centre for cell biology of infectious pathogens (WAACCBIP, University of Ghana) to set the research priorities and training opportunities to the centre.
JB was elected fellow of the American Academy of Microbiology (2023), demonstrating his originality and leadership in Microbiology.
Affiliations
Teaching
Currently, Prof Bengoechea has no teaching commitments due to his role as Dean of the Faculty. He previously tought at the undergraduate and postgraduate level on fundamenatl aspects of Microbiology, Microbial Pathogensis, Innate Immunity and defence against infections, AMR and new therapeutics.
Research
Bengoechea’s independent research career covers two phases. As an early-career PI, his focus was on the biosynthesis of lipopolysaccharides (LPS), and their contribution to virulence, immune evasion, and antibiotic resistance His record in this area contains several important “firsts”. He delineated the role of the LPS polysaccharide sections in Yersinia enterocolitica virulence. Y. enterocolitica was the first pathogen for which the contribution of the LPS core to virulence was rigorously proven, fulfilling Koch’s molecular postulates. This pioneering work catalyzed similar studies in other pathogens including Brucella, Salmonella typhimurium, and K. pneumoniae. He has contributed to dissect the impact of lipid A structural changes on the recognition of the LPS pattern by the host by demonstrating the effect of Yersinia LpxR deacylase to remodel the lipid A to limit inflammation, and the LpxO-controlled lipid A hydroxylation in K. pneumoniae and Acinetobacter baumannii interactions with the immune system. His work established lipid A hydroxylation as new immune evasion mechanism. In another breakthrough study, his team reported for the first time the lipid A produced by any pathogen in vivo. His findings demonstrated Klebsiella remodels its lipid A in a tissue-dependent manner. The in vivo lipid A pattern reduces the activation of inflammatory responses and mediates resistance to antimicrobial peptides. His work has also provided mechanistic insights into the antimicrobial resistance to polymyxins, last-line antibiotics to treat multidrug resistant infections. His team reported that the addition of phosphoethanolamine to the hepta-acylated lipid A confers colistin resistance in polymyxin B resistant isolates of A. baumannii. He determined for the first time the extensive lipid A remodeling triggered by the mutation of the mgrB regulator. More than 50% of K. pneumoniae isolates resistant to colistin harbour mgrB mutations. MgrB-governed lipid A remodeling results in an increase in the virulence of K. pneumoniae. This finding is supporting further the notion that antibiotic resistance is not inexorably linked with subdued virulence.
In the second phase of his career, Bengoechea established a program investigating the biology and host-pathogen interactions of the global threat Klebsiella and much of his current focus lies in this topic. His work has led to a paradigm shift by demonstrating that the pathogen has evolved to suppress innate immunity. This strategy complements the widely accepted stealth behavior of Klebsiella based on avoiding the recognition by innate receptors and effectors in a capsule-dependent manner. His work uncovered novel non-redundant anti-immunology factors including the classical pullulanase type II secretion system for which its role in virulence was unknown, and OmpA. At the cellular level, his findings have demonstrated Klebsiella has evolved to hijack host proteins, deubiquinases, phosphatases and desumoylases, to control signaling pathways to damplen inflammation. His research has illustrated how bacteria can manipulate innate receptors to promote infection. In vivo, his research has illustrated a hitherto unknown way to polarize lung macrophages to overcome host restriction during pneumonia. Recently, he has embarked on the characterization of the role of the type VI secretion system on Klebsiella pathogenesis. His group provided the first characterization of the system, and discovered the antimicrobial functions of the system in vitro and in vivo, and illustrated its anti-host functions including mitochondria fragmentation and induction of immune checkpoint inhibitor PD-L1 to promote infection. He has developed innovative research models, including the Galleria mellonella insect infection model, the porcine and human ex vivo lung infection model, and a mouse model to investigate Klebsiella gut colonization in immunocompetent mice without need of perturbing the microbiome. He has pioneered the use of single cell approaches, scRNA-seq and mass cytometry, to study the infection biology of antibiotic-resistant infections. Bengoechea has published more than 100 articles in top journals, being the corresponding author in most of them. Bengoechea is highly regarded as a world-renowned authority in Klebsiella pathogenesis. This two decades knowledge platform has resulted in collaborations with AstraZeneca to develop the first host-directed therapeutics against Klebsiella funded by the MRC, with GSK to develop new antibody-based therapeutics against Klebsiella, and with VaxDyn to trial a Klebsiella vaccine funded by Carb-X. His work is supported by BBSRC and MRC (£6,4 M since 2013). JB has also attracted substantial EU funding as consortium leader in excess of £5 M. This work was lauded by the EU Commission in a report translated to five languages