Biography

Areas of specialism

Infectious diseases, AMR, molecular microbiology, in vitro animal models and diagnostics

University roles and responsibilities

  • SVM ECR representative
  • FHMS ECR representative

    Affiliations and memberships

    Microbiology Society
    Champion
    Society for Applied Microbiology
    Member
    The Australian Society for Microbiology
    Communication ambassador alumni
    European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
    Member

    Research

    Research interests

    My publications

    Publications

    MARWA M. HASSAN, Niamh E Harrington, Esther Sweeney, Freya Harrison (2021)Predicting Antibiotic-Associated Virulence of Pseudomonas aeruginosa Using an ex vivo Lung Biofilm Model, In: Frontiers in microbiology11568510 Frontiers Media

    Bacterial biofilms are known to have high antibiotic tolerance which directly affects clearance of bacterial infections in people with cystic fibrosis (CF). Current antibiotic susceptibility testing methods are either based on planktonic cells or do not reflect the complexity of biofilms . Consequently, inaccurate diagnostics affect treatment choice, preventing bacterial clearance and potentially selecting for antibiotic resistance. This leads to prolonged, ineffective treatment. In this study, we use an lung biofilm model to study antibiotic tolerance and virulence of . Sections of pig bronchiole were dissected, prepared and infected with clinical isolates of and incubated in artificial sputum media to form biofilms, as previously described. Then, lung-associated biofilms were challenged with antibiotics, at therapeutically relevant concentrations, before their bacterial load and virulence were quantified and detected, respectively. The results demonstrated minimal effect on the bacterial load with therapeutically relevant concentrations of ciprofloxacin and meropenem, with the latter causing an increased production of proteases and pyocyanin. A combination of meropenem and tobramycin did not show any additional decrease in bacterial load but demonstrated a slight decrease in total proteases and pyocyanin production. In this initial study of six clinical isolates of showed high levels of antibiotic tolerance, with minimal effect on bacterial load and increased proteases production, which could negatively affect lung function. Thus, the lung model has the potential to be effectively used in larger studies of antibiotic tolerance in -like biofilms, and show how sub optimal antibiotic treatment of biofilms may potentially contribute to exacerbations and eventual lung failure. We demonstrate a realistic model for understanding antibiotic resistance and tolerance in biofilms clinically and for molecules screening in anti-biofilm drug development.

    Esther Sweeney, Niamh E Harrington, Alicia G Harley Henriques, MARWA M. HASSAN, Branagh Crealock-Ashurst, Alan R Smyth, Matthew N Hurley, María Ángeles Tormo-Mas, Freya Harrison (2020)An ex vivo cystic fibrosis model recapitulates key clinical aspects of chronic Staphylococcus aureus infection, In: Microbiology (Society for General Microbiology)167(1)pp. 1-15

    Staphylococcus aureus is the most prevalent organism isolated from the airways of people with cystic fibrosis (CF), predominantly early in life. Yet its role in the pathology of lung disease is poorly understood. In mice, and many experiments using cell lines, the bacterium invades cells or interstitium, and forms abscesses. This is at odds with the limited available clinical data: interstitial bacteria are rare in CF biopsies and abscesses are highly unusual. Bacteria instead appear to localize in mucus plugs in the lumens of bronchioles. We show that, in an established ex vivo model of CF infection comprising porcine bronchiolar tissue and synthetic mucus, S. aureus demonstrates clinically significant characteristics including colonization of the airway lumen, with preferential localization as multicellular aggregates in mucus, initiation of a small colony variant phenotype and increased antibiotic tolerance of tissue-associated aggregates. Tissue invasion and abscesses were not observed. Our results may inform ongoing debates relating to clinical responses to S. aureus in people with CF.

    TJ O'Brien, MARWA M. HASSAN, Freya Harrison, Martin Welch (2021)An in vitro model for the cultivation of polymicrobial biofilms under continuous-flow conditions, In: F1000 research10

    The airways of people with cystic fibrosis (CF) are often chronically colonised with a diverse array of bacterial and fungal species. However, little is known about the relative partitioning of species between the planktonic and biofilm modes of growth in the airways. Existing in vivo and in vitro models of CF airway infection are ill-suited for the long-term recapitulation of mixed microbial communities. Here we describe a simple, in vitro continuous-flow model for the cultivation of polymicrobial biofilms and planktonic cultures on different substrata. Our data provide evidence for inter-species antagonism and synergism in biofilm ecology. We further show that the type of substratum on which the biofilms grow has a profound influence on their species composition. This happens without any major alteration in the composition of the surrounding steady-state planktonic community. Our experimentally-tractable model enables the systematic study of planktonic and biofilm communities under conditions that are nutritionally reminiscent of the CF airway microenvironment, something not possible using any existing in vivo models of CF airway infection.

    MARWA M. HASSAN, Tamer M Samir, Hassan M.E Azzazy (2013)Unmodified gold nanoparticles for direct and rapid detection of Mycobacterium tuberculosis complex, In: Clinical biochemistry46(7-8)pp. 633-637 Elsevier Inc

    This work aims to develop rapid nano-gold assay prototypes for specific detection of Mycobacterium tuberculosis complex (MTBC). Spherical gold nanoparticles (AuNPs, 14nm) were synthesized by citrate reduction method and characterized by spectrophotometry and SEM. MTB 16s rDNA regions were amplified by PCR and amplicons were detected using genus- and species-specific oligotargeters and AuNPs. In a second prototype, MTBC unamplified genomic DNA was directly detected using species-specific oligo-targeters and AuNPs. Detection limits were 1ng for PCR product and 40ng for genomic DNA. The nano-gold prototype detected 45 positive genomic DNA samples which were also positive with automated liquid culture system (BACTEC™ MGIT™) and semi-nested PCR (100% concordance). Following DNA extraction, using standard procedures, the TB nano-gold prototype turnaround time is about 1h. We have developed nano-gold assay prototype for direct and inexpensive detection of MTBC. The developed prototypes are simple, sensitive, rapid and can substitute PCR-based detection. The developed assay may show potential in the clinical diagnosis of TB especially in developing countries. [Display omitted] ► Unmodified spherical AuNPs were used for detection of MTBC DNA. ► The AuNP TB assay generated results concordant to bacterial culture. ► TB assay turnaround time was about 1h after DNA extraction. ► The detection limit was 1ng for PCR product and 40ng for genomic DNA. ► TB AuNP prototypes were simple, sensitive, rapid, and inexpensive.

    MARWA MOHSEN HUSSAIN ALI HASSAN, Andrea Ranzoni, Matthew Cooper (2018)A nanoparticle-based method for culture-free bacterial DNA enrichment from whole blood, In: Biosensors & bioelectronics99pp. 150-155

    Point-of-care (POC) diagnostics are one of the quick and sensitive detection approaches used in current clinical applications, but always face a performance tradeoff between time-to-result and assay sensitivity. One critical setting where these limitations are evident is the detection of sepsis, where 6-10mL of whole blood may contain as little as one bacterial colony forming unit (cfu). The large sample volume, complex nature of the sample and low analyte concentration necessitates signal enhancement using culture-based or molecular amplification techniques. In the time-critical diagnosis of sepsis, waiting for up to 24h to produce sufficient DNA for analysis is not possible. As a consequence, there is a need for integrated sample preparation methods that could enable shorter detection times, whilst maintaining high analytical performance. We report the development of a culture-free bacterial enrichment method to concentrate bacteria from whole blood in less than 3h. The method relies on triple-enrichment steps to magnetically concentrate bacterial cells and their DNA with a 500-fold reduction in sample volume (from 10 to 0.02mL). Using this sample preparation method, sensitive qPCR detection of the extracted S. aureus bacterial DNA was achieved with a detection limit of 5±0.58cfu/mL within a total elapsed time of 4h; much faster than conventional culture-based approaches. The method could be fully automated for integration into clinical practice for point-of-care or molecular detection of bacterial DNA from whole blood.

    Arnoud H M van Vliet, MARWA M. HASSAN, Owen Higgins, LA Burke, Louise O'Connor, D Morris, ROBERTO MARCELLO LA RAGIONE, TC Smith (2020)WorldCOM Deliverable 1: Prevalence of ESBL subtypes in bacterial pathogens and a sequence database of selected alleles Zenodo

    OHEJP Project: WorldCOM, Deliverable 1, Work Package 1. This dataset is connected to Work Package 1, Task1 of the WorldCOM consortium grant within the One Health EJP group. The aim was to analyse publicly available sequences for antimicrobial resistance genes associated with Salmonella, Campylobacter and E. coli. For the initial phase of this work package, we have focused on ESBL-related AMR genes. As these genes are absent from Campylobacter, we have not included this bacterium in these analyses, and have used the important pathogens Klebsiella and Acinetobacter. All types and subtypes of Extended Spectrum β-Lactamases (ESBLs) and plasmid-mediated colistin resistance genes have been analysed for frequency among reported and extracted sequences. High frequency resistant genes subtypes have been highlighted for further sequence analysis to illustrate geographic distribution and geographic-specific single nucleotide polymorphisms (SNPs). The data shown are work in progress.

    Mark Blaskovich, Matthew Cooper, Andrea Ranzoni, Wanida Phetsang, MARWA M. HASSAN (2020)Glycopeptide antibiotic constructs

    A construct comprising: (i) an optionally derivatized glycopeptide antibiotic; (ii) a nanoparticle; and (iii) a first linker connecting (i) and (ii) is provided. The construct may further comprise a second linker located between the first linker and (ii). The nanoparticle may be a separation nanoparticle, such as a magnetic separation nanoparticle. The glycopeptide antibiotic may be selected from the group consisting: of vancomycin; teicoplanin; oritavancin; telavancin; chloroeremomycin; and balhimycin. Also provided are related methods of producing and using the construct, such as methods of separation of bacteria from a sample by binding the bacteria to the construct.

    MARWA M. HASSAN, Andrea Ranzoni, Wanida Phetsang, Mark A T Blaskovich, Matthew Cooper (2017)Surface Ligand Density of Antibiotic-Nanoparticle Conjugates Enhances Target Avidity and Membrane Permeabilization of Vancomycin-Resistant Bacteria, In: Bioconjugate chemistry28(2)pp. 353-361

    Many bacterial pathogens have now acquired resistance toward commonly used antibiotics, such as the glycopeptide antibiotic vancomycin. In this study, we show that immobilization of vancomycin onto a nanometer-scale solid surface with controlled local density can potentiate antibiotic action and increase target affinity of the drug. Magnetic nanoparticles were conjugated with vancomycin and used as a model system to investigate the relationship between surface density and drug potency. We showed remarkable improvement in minimum inhibitory concentration against vancomycin-resistant strains with values of 13-28 μg/mL for conjugated vancomycin compared to 250-4000 μg/mL for unconjugated vancomycin. Higher surface densities resulted in enhanced affinity toward the bacterial target compared to that of unconjugated vancomycin, as measured by a competition experiment using a surrogate ligand for bacterial Lipid II, N-Acetyl-l-Lys-d-Ala-d-Ala. High density vancomycin nanoparticles required >64 times molar excess of ligand (relative to the vancomycin surface density) to abrogate antibacterial activity compared to only 2 molar excess for unconjugated vancomycin. Further, the drug-nanoparticle conjugates caused rapid permeabilization of the bacterial cell wall within 2 h, whereas no effect was seen with unconjugated vancomycin, suggesting additional modes of action for the nanoparticle-conjugated drug. Hence, immobilization of readily available antibiotics on nanocarriers may present a general strategy for repotentiating drugs that act on bacterial membranes or membrane-bound targets but have lost effectiveness against resistant bacterial strains.