Thesis title: Establishing the mechanistic basis of the transcriptional regulators (RamA, RarA, MarA and SoxS) in the evolution of antibiotic susceptibility and pathogenicity in K. pneumoniae


I was born and raised in Greece in the city of Athens. Due to some eventful events in my life, I decided at the age of 13 to devote my life in research centred around medicine. Upon the completion of school I decided at the age of 17 that the UK was the best place to carry forward my purpose. During my bachelors degree in Biomedical Sciences I was inspired by Dr. Thamarai Dorai-Schneiders and decided to focus on antimicrobial resistance (AMR). Since then I have been investigating multiple mechanisms in K.pneumoniae to shine light on the threat it will certainly impose on public health. 


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Undergraduate teaching

Active demonstrator in courses of the Biomedical Sciences degree organized by UoE. 

Research summary

Elucidating the intrinsic resistance mechanisms that K.pneumoniae employs, and their importance in generating an AMR phenotype, is essential to developing a comprehensive and effective antimicrobial strategy. Furthermore, identifying the pathways of specific resistance mechanisms contributing to AMR, presents potential targets for inhibitory drugs in combination with existing antimicrobial giving rise to novel treatment regimes. 

Current research interests

To survive in changing environments, bacteria have evolved mechanisms to adapt through the expression of appropeiate gene. Antimicrobial agent and stressor exposure of Enterobavteriacea causes the activation of the AraC/XylS type of transcriptional regulators , including RamA, RarA, MarA and SoxS. These act as global regulators to alter gene expression allowing for favourable fitness in the presence of bacteriocidal substances. Increased expression of marA, rarA, ramA, and soxS up-regulates efflux channel expression to allow detoxification of the cell. Moreover, this expression has been linked to clinically significant strains of K.pneumoniae.

Past research interests

Lay summary of thesis on CrrAB TCS in Klebsiella pneumoniae- Bacterial infections have been a major threat to humanity for centuries. Upon the introduction of antibiotic treatment regimes in the 20th century the threat was alleviated. In the past decade, the extensive use of antibiotics resulted in the emergence of resistance to virtually all of them, the effect of which will result to an exponential rise in mortality and morbidity. It is essential to characterize the underlying mechanism of resistance to counter its effect through the development of novel treatments. In the present research, the pathway of resistant, and secondary effects arising from its activation, to the last resort antibiotic (colistin) were analyzed. One of the most clinically significant bacteria, namely Klebsiella pneumoniae was used as the vector to analyze the interplay between colistin resistant and secondary effects. It is known that regulatory proteins harboring mutations can extensively decorate a molecule (LPS) located in the outer membrane of K.pneumoniae resulting in colistin resistance. The major altered proteins are PhoPQ and PmrAB and the recently identified CrrAB which is now believed to play a major role. The understudied CrrAB protein is of the same nature as PhoPQ and PmrAB, but in a previous publication there where faint evidence for the cooccurrence of other effects arising in combination with colistin resistance in the presence of CrrAB mutations. To investigate the nature of these effects, five distinct mutations in CrrAB were recreated. Three of these mutations exhibited a novel effect in K.pneumoniae, the formation of an external layer of sugars in combination with colistin resistance. This external layer, namely capsule, is important in the protection of bacteria from multiple external stressors. These stressors include antibiotics and functions of the immune system of humans. The formation of capsule in K.pneumoniae expressing a mutated CrrAB protein was then attributed to the upregulation of three proteins participating in the carbon cycle. It is not yet known if these proteins are directly or indirectly controlled by the mutated CrrAB. Moreover, the major PhoPQ protein appears to play no part in the formation of the outer layer but is crucial in the rise of colistin resistance. Since, alterations in the PhoPQ pathway are the leading cause for colistin resistance it is essential to describe its interaction with the CrrAB protein. Through deletion of the PhoPQ protein and overproduction of the altered CrrAB protein known to cause capsule production it was found that capsule production is solely an effect of CrrAB. On the other hand, colistin resistance was abolished