Dr Karl Hassan

Dr Karl Hassan

Senior Lecturer

School of Environmental and Life Sciences

Career Summary

Biography

Dr Karl Hassan applies cutting edge tools in molecular microbiology, genomics, and biochemistry to study our bacterial friends and foes. Karl completed his PhD at the University of Sydney, and held Research Fellowships at Macquarie University, and the University of Leeds, UK, before joining the University of Newcastle as a Senior Lecturer. Karl’s research fits into three general themes.

Antimicrobial drug resistance in hospital acquired bacteria

Hospital-acquired infections caused by pathogenic bacteria cost billions of dollars each year and increase patient pain and morbidity. These infections are becoming increasingly difficult to treat due to rising levels of drug resistance in the pathogens. The threat caused by drug resistant pathogens is recognised by the WHO as one of the major challenges facing humanity. A large part of Karl’s research is focused on understanding the mechanisms of antimicrobial resistance and virulence in human bacterial pathogens, and on antimicrobial drug discovery. 

Karl applies comparative and functional genomic technologies to identify key drug resistance factors in pathogens, and to map out the regulatory circuits that control their expression. Using transcriptomics to monitor bacterial responses to common antimicrobials, Karl identified a completely new class of multidrug resistance determinant that is broadly conserved in Gram-negative bacterial pathogens (PNAS 2013; mBio 2015). Karl has several current research projects investigating these novel resistance determinants. In recent research Karl has pioneered the use of next-generation transposon sequencing methods in combination with flow-sorting to identify the genetic factors that control the concentration of antimicrobials in bacteria (mBio 2016). Low accumulation of drugs into many serious pathogens is a primary cause of treatment failure and a major road block in our development of new drugs. The new method Karl developed has a broad range of important future applications in areas of antimicrobial resistance, drug development and synthetic biology.


Membrane transport systems

Biological membranes are fundamental to cellular life. These thin layers of lipids provide permeability barriers that help to prevent the entry of toxins and the exit of nutrients from cells. Membrane transport systems are proteins that sit in biological membranes and facilitate the movement of ions or molecules from one side to another. 

Karl developed an interest in transport proteins during his PhD where he investigated the molecular transport mechanisms of multidrug efflux systems in the hospital pathogen Staphylococcus aureus. Karl now studies membrane transport systems on a genome-wide level, and is a member of the TransportDB database development team. This interactive database lists complete sets of transporters identified in fully sequenced organisms using a tailored bioinformatic prediction pipeline. Using functional genomics Karl identified a new family of multidrug efflux systems, the first new family of microbial drug efflux pumps to be identified in 15 years (PNAS 2013; mBio 2015). Karl is applying sophisticated biochemical and biophysical methods to characterise the molecular mechanism(s) of transport operating in these pumps, determine their potential roles in the bacterial virulence, and identify potential small molecule inhibitors for these pumps.


Plant commensal biocontrol bacteria

Food security is an issue of increasing importance due to unpredictable climate trends and increasing global population growth. The capacity to control plant diseases is of paramount importance to reliable crop production. Natural plant-colonising bacteria represent a powerful tool for the protection of crops from disease, which would alleviate the need for harmful agrochemicals. Karl has an ongoing interest in examining mechanisms of plant pathogen suppression by biocontrol bacteria. 

Karl has current research projects investigating plant commensal biocontrol strains of Bacillus and Pseudomonas. Using comparative and functional genomics Karl has identified several novel gene clusters that encode biocontrol factors, such as secreted secondary metabolites, and determined environmental conditions that promote their expression. Karl led the comparative genomics components of one the most comprehensive analysis of plant associated biocontrol Pseudomonas strains conducted to date (PLoS Genetics 2012), and some of the first transcriptomic analyses to be conducted in a biocontrol bacteria (Environmental Microbiology 2010). Karl is currently expanding this work to examine the molecular determinants of plant colonisation, using transcriptomic and transposon sequencing approaches.

Qualifications

  • Doctor of Philosophy, University of Sydney
  • Bachelor of Biotechnology (Honours), University of Wollongong

Keywords

  • antimicrobial resistance
  • membrane transport
  • microbial genomics

Fields of Research

Code Description Percentage
060599 Microbiology not elsewhere classified 35
060199 Biochemistry and Cell Biology not elsewhere classified 30
060408 Genomics 35

Professional Experience

UON Appointment

Title Organisation / Department
Senior Lecturer University of Newcastle
School of Environmental and Life Sciences
Australia
Edit

Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Chapter (3 outputs)

Year Citation Altmetrics Link
2017 Li L, Tetu SG, Paulsen IT, Hassan KA, 'A transcriptomic approach to identify novel drug efflux pumps in bacteria', Bacterial Multidrug Exporters: Methods and Protocols, Methods in Molecular Biology, Springer, Berlin (2017)
DOI 10.1007/978-1-4939-7454-2_12
2013 Eijkelkamp BA, Hassan KA, Paulsen IT, Brown MH, 'The Role of Efflux Pumps in the Nosocomial Pathogens Staphylococcus aureus and Acinetobacter baumannii', Microbial Efflux Pumps: Current Research, Horizon Scientific Press, Norfolk, UK 123-143 (2013)
2011 Hassan KA, Paulsen IT, 'Clostridium perfringens', Genomes of Foodborne and Waterborne Pathogens, American Society of Microbiology, Washington, DC 213-221 (2011)

Journal article (51 outputs)

Year Citation Altmetrics Link
2017 Paulsen IT, Cain AK, Hassan KA, 'Physical enrichment of transposon mutants from saturation mutant libraries using the TraDISort approach', Mobile Genetic Elements, 7 1-7 (2017)
DOI 10.1080/2159256X.2017.1313805
2017 Elbourne LDH, Tetu SG, Hassan KA, Paulsen IT, 'TransportDB 2.0: a database for exploring membrane transporters in sequenced genomes from all domains of life', NUCLEIC ACIDS RESEARCH, 45 D320-D324 (2017)
DOI 10.1093/nar/gkw1068
Citations Scopus - 4Web of Science - 5
2017 Hassan KA, Pederick VG, Elbourne LDH, Paulsen IT, Paton JC, McDevitt CA, Eijkelkamp BA, 'Zinc stress induces copper depletion in Acinetobacter baumannii', BMC MICROBIOLOGY, 17 (2017)
DOI 10.1186/s12866-017-0965-y
2017 Hassan KA, Fagerlund A, Elbourne LDH, Voros A, Kroeger JK, Simm R, et al., 'The putative drug efflux systems of the Bacillus cereus group', PLOS ONE, 12 (2017)
DOI 10.1371/journal.pone.0176188
2016 Li L, Hassan KA, Brown MH, Paulsen IT, 'Rapid multiplexed phenotypic screening identifies drug resistance functions for three novel efflux pumps in Acinetobacter baumannii', Journal of Antimicrobial Chemotherapy, dkv460-dkv460 (2016)
2016 Lim CK, Penesyan A, Hassan KA, Loper JE, Paulsen IT, 'Disruption of transporters affiliated with enantio-pyochelin biosynthesis gene cluster of Pseudomonas protegens Pf-5 has pleiotropic effects', PLoS One, 11 (2016) [C1]
DOI 10.1371/journal.pone.0159884
Citations Scopus - 2Web of Science - 2
2016 Hassan KA, Cain AK, Huang T, Liu Q, Elbourne LDH, Boinett CJ, et al., 'Fluorescence-Based Flow Sorting in Parallel with Transposon Insertion Site Sequencing Identifies Multidrug Efflux Systems in Acinetobacter baumannii', mBio, 7 (2016) [C1]
DOI 10.1128/mBio.01200-16
2015 Kroeger JK, Hassan K, Voeroes A, Simm R, Saidijam M, Bettaney KE, et al., 'Bacillus cereus efflux protein BC3310-a multidrug transporter of the unknown major facilitator family, UMF-2', FRONTIERS IN MICROBIOLOGY, 6 (2015) [C1]
DOI 10.3389/fmicb.2015.01063
Citations Scopus - 1Web of Science - 1
2015 Hassan KA, Elbourne LDH, Tetu SG, Melville SB, Rood JI, Paulsen IT, 'Genomic analyses of Clostridium perfringens isolates from five toxinotypes', RESEARCH IN MICROBIOLOGY, 166 255-263 (2015) [C1]
DOI 10.1016/j.resmic.2014.10.003
Citations Scopus - 9Web of Science - 10
2015 Hassan KA, Elbourne LDH, Li L, Gamage HKAH, Liu Q, Jackson SM, et al., 'An ace up their sleeve: a transcriptomic approach exposes the Acel efflux protein of Acinetobacter baumannii and reveals the drug efflux potential hidden in many microbial pathogens', FRONTIERS IN MICROBIOLOGY, 6 (2015) [C1]
DOI 10.3389/fmicb.2015.00333
Citations Scopus - 3Web of Science - 2
2015 Song C, van der Voort M, van de Mortel J, Hassan KA, Elbourne LDH, Paulsen IT, et al., 'The Rsm regulon of plant growth-promoting Pseudomonas fluorescens SS101: role of small RNAs in regulation of lipopeptide biosynthesis', MICROBIAL BIOTECHNOLOGY, 8 296-310 (2015) [C1]
DOI 10.1111/1751-7915.12190
Citations Scopus - 5Web of Science - 3
2015 Hassan KA, Liu Q, Henderson PJF, Paulsena IT, 'Homologs of the Acinetobacter baumannii AceI Transporter Represent a New Family of Bacterial Multidrug Efflux Systems', MBIO, 6 (2015) [C1]
DOI 10.1128/mBio.01982-14
Citations Scopus - 24Web of Science - 18
2015 Cameron DR, Jiang JH, Hassan KA, Elbourne LDH, Tuck KL, Paulsen IT, Peleg AY, 'Insights on virulence from the complete genome of staphylococcus capitis', Frontiers in Microbiology, 6 (2015) [C1]

© 2015 Cameron, Jiang, Hassan, Elbourne, Tuck, Paulsen and Peleg. Staphylococcus capitis is an opportunistic pathogen of the coagulase negative staphylococci (CoNS). Functional g... [more]

© 2015 Cameron, Jiang, Hassan, Elbourne, Tuck, Paulsen and Peleg. Staphylococcus capitis is an opportunistic pathogen of the coagulase negative staphylococci (CoNS). Functional genomic studies of S. capitis have thus far been limited by a lack of available complete genome sequences. Here, we determined the closed S. capitis genome and methylome using Single Molecule Real Time (SMRT) sequencing. The strain, AYP1020, harbors a single circular chromosome of 2.44 Mb encoding 2304 predicted proteins, which is the smallest of all complete staphylococcal genomes sequenced to date. AYP1020 harbors two large mobile genetic elements; a plasmid designated pAYP1020 (59.6 Kb) and a prophage, FAYP1020 (48.5 Kb). Methylome analysis identified significant adenine methylation across the genome involving two distinct methylation motifs (1972 putative 6-methyladenine (m6A) residues identified). Putative adenine methyltransferases were also identified. Comparative analysis of AYP1020 and the closely related CoNS, S. epidermidis RP62a, revealed a host of virulence factors that likely contribute to S. capitis pathogenicity, most notably genes important for biofilm formation and a suite of phenol soluble modulins (PSMs); the expression/production of these factors were corroborated by functional assays. The complete S. capitis genome will aid future studies on the evolution and pathogenesis of the coagulase negative staphylococci.

DOI 10.3389/fmicb.2015.00980
Citations Scopus - 6Web of Science - 6
2015 Timms VJ, Hassan KA, Mitchell HM, Neilan BA, 'Comparative genomics between human and animal associated subspecies of the Mycobacterium avium complex: a basis for pathogenicity', BMC GENOMICS, 16 (2015) [C1]
DOI 10.1186/s12864-015-1889-2
Citations Scopus - 4Web of Science - 3
Co-authors Brett Neilan
2014 Hassan KA, Paulsen IT, Elbourne LD, Ren Q, Cameron AD, Henderson PJ, others, 'Microbial solute transporters (2014)
2014 Mackie AM, Hassan KA, Paulsen IT, Tetu SG, 'Biolog phenotype microarrays for phenotypic characterization of microbial cells', Methods in Molecular Biology, 1096 123-130 (2014)

Biolog Phenotype MicroArrays for microorganisms provide a high-throughput method for the global analysis of microbial growth phenotypes. Using a colorimetric reaction that is indi... [more]

Biolog Phenotype MicroArrays for microorganisms provide a high-throughput method for the global analysis of microbial growth phenotypes. Using a colorimetric reaction that is indicative of respiration, these microplate assays measure the response of an individual strain or microbial community to a large and diverse range of nutrients and chemicals. Phenotype MicroArrays have been used to study gene function and to improve genome annotation in single microorganisms and for physiological profiling of bacterial communities. The microplate system can be used to obtain a comprehensive overview of metabolic capability, or it can be tailored, through the use of subsets of plates, to address specific research needs. © 2014 Springer Science+Business Media, LLC.

DOI 10.1007/978-1-62703-712-9_10
Citations Scopus - 8
2014 Brzoska AJ, Hassan KA, 'Quantitative PCR for detection of mRNA and gDNA in environmental isolates', Methods in Molecular Biology, 1096 25-42 (2014)

Quantitative PCR is used to gauge the abundance of specific nucleic acid species within purified samples. Due to its high sensitivity and minimal operation costs, this method is r... [more]

Quantitative PCR is used to gauge the abundance of specific nucleic acid species within purified samples. Due to its high sensitivity and minimal operation costs, this method is routinely applied in modern molecular bioscience laboratories. Nonetheless, all quantitative PCR experiments must include several carefully designed, yet simple, controls to ensure the reliability of the analyses. The aim of this chapter is to provide basic quantitative PCR methods, from primer design through data analysis, that are generally applicable to studies in microbiology. These methods allow the abundance of targeted RNA or DNA molecules to be determined in nucleic acid samples purified from a variety of biological sources. © 2014 Springer Science+Business Media, LLC.

DOI 10.1007/978-1-62703-712-9_3
Citations Scopus - 2
2014 Eijkelkamp BA, Stroeher UH, Hassan KA, Paulsen IT, Brown MH, 'Comparative analysis of surface-exposed virulence factors of Acinetobacter baumannii', BMC GENOMICS, 15 (2014) [C1]
DOI 10.1186/1471-2164-15-1020
Citations Scopus - 19Web of Science - 18
2014 Voros A, Simm R, Slamti L, Mckay MJ, Hegna IK, Nielsen-LeRoux C, et al., 'SecDF as Part of the Sec-Translocase Facilitates Efficient Secretion of Bacillus cereus Toxins and Cell Wall-Associated Proteins', PLOS ONE, 9 (2014) [C1]
DOI 10.1371/journal.pone.0103326
Citations Scopus - 8Web of Science - 9
2014 Hassan KA, Elbourne LDH, Tetu SG, Johnson EA, Paulsen IT, 'Genome sequence of the neurotoxigenic Clostridium butyricum strain 5521', Genome Announcements, 2 (2014) [C1]

© 2014 Hassan et al. Clostridium strains from six phylogenetic groups, C. botulinum groups I to IV, C. baratii, and C. butyricum, display the capacity to produce botulinum neurot... [more]

© 2014 Hassan et al. Clostridium strains from six phylogenetic groups, C. botulinum groups I to IV, C. baratii, and C. butyricum, display the capacity to produce botulinum neurotoxin. Here, we present the genome sequence of a C. butyricum isolate, the neurotoxigenic strain 5521, which encodes the type E botulinum neurotoxin.

DOI 10.1128/genomeA.00632-14
Citations Scopus - 3
2013 Eijkelkamp BA, Stroeher UH, Hassan KA, Elbourne LDH, Paulsen IT, Brown MH, 'H-NS Plays a Role in Expression of Acinetobacter baumannii Virulence Features', INFECTION AND IMMUNITY, 81 2574-2583 (2013) [C1]
DOI 10.1128/IAI.00065-13
Citations Scopus - 26Web of Science - 25
2013 Hassan KA, Jackson SM, Penesyan A, Patching SG, Tetu SG, Eijkelkamp BA, et al., 'Transcriptomic and biochemical analyses identify a family of chlorhexidine efflux proteins', PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110 20254-20259 (2013) [C1]
DOI 10.1073/pnas.1317052110
Citations Scopus - 32Web of Science - 32
2013 Lim CK, Penesyan A, Hassan KA, Loper JE, Paulsen IT, 'Effect of Tannic Acid on the Transcriptome of the Soil Bacterium Pseudomonas protegens Pf-5', APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 79 3141-3145 (2013) [C1]
DOI 10.1128/AEM.03101-12
Citations Scopus - 4Web of Science - 3
2013 Stockwell VO, Davis EW, Carey A, Shaffer BT, Mavrodi DV, Hassan KA, et al., 'pA506, a Conjugative Plasmid of the Plant Epiphyte Pseudomonas fluorescens A506', APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 79 5272-5282 (2013) [C1]
DOI 10.1128/AEM.01354-13
Citations Scopus - 7Web of Science - 5
2013 Lim CK, Hassan KA, Penesyan A, Loper JE, Paulsen IT, 'The effect of zinc limitation on the transcriptome of Pseudomonas protegens Pf-5', ENVIRONMENTAL MICROBIOLOGY, 15 702-715 (2013) [C1]
DOI 10.1111/j.1462-2920.2012.02849.x
Citations Scopus - 23Web of Science - 23
2013 Tetu SG, Johnson DA, Varkey D, Phillippy K, Stuart RK, Dupont CL, et al., 'Impact of DNA damaging agents on genome-wide transcriptional profiles in two marine Synechococcus species', FRONTIERS IN MICROBIOLOGY, 4 (2013) [C1]
DOI 10.3389/fmicb.2013.00232
Citations Scopus - 10Web of Science - 7
2013 Farrugia DN, Elbourne LDH, Hassan KA, Eijkelkamp BA, Tetu SG, Brown MH, et al., 'The Complete Genome and Phenome of a Community-Acquired Acinetobacter baumannii', PLOS ONE, 8 (2013) [C1]
DOI 10.1371/journal.pone.0058628
Citations Scopus - 29Web of Science - 26
2013 Venturini C, Hassan KA, Chowdhury PR, Paulsen IT, Walker MJ, Djordjevic SP, 'Sequences of Two Related Multiple Antibiotic Resistance Virulence Plasmids Sharing a Unique IS26-Related Molecular Signature Isolated from Different Escherichia coli Pathotypes from Different Hosts', PLOS ONE, 8 (2013) [C1]
DOI 10.1371/journal.pone.0078862
Citations Scopus - 10Web of Science - 9
2013 Hassan KA, Tetu SG, Elbourne LDH, Johnson EA, Paulsen IT, 'Genome sequence of the group III Clostridium botulinum strain Eklund-C', Genome Announcements, 1 (2013) [C1]

© 2013 Hassan et al. The neurotoxins produced by Clostridium botulinum strains are among the world's most potent toxins and are the causative agents of paralytic botulism. H... [more]

© 2013 Hassan et al. The neurotoxins produced by Clostridium botulinum strains are among the world's most potent toxins and are the causative agents of paralytic botulism. Here, we present the draft genome sequence of the group III C. botulinum strain Eklund-C, including a pseudolysogen-like bacteriophage that harbors the type C neurotoxin operon.

DOI 10.1128/genomeA.00044-13
Citations Scopus - 5
2013 Brzoska AJ, Hassan KA, de Leon EJ, Paulsen IT, Lewis PJ, 'Single-Step Selection of Drug Resistant Acinetobacter baylyi ADP1 Mutants Reveals a Functional Redundancy in the Recruitment of Multidrug Efflux Systems', PLOS ONE, 8 (2013) [C1]
DOI 10.1371/journal.pone.0056090
Citations Scopus - 11Web of Science - 10
Co-authors Peter Lewis
2012 Loper JE, Hassan KA, Mavrodi DV, Davis EW, Lim CK, Shaffer BT, et al., 'Comparative Genomics of Plant-Associated Pseudomonas spp.: Insights into Diversity and Inheritance of Traits Involved in Multitrophic Interactions', PLOS GENETICS, 8 (2012) [C1]
DOI 10.1371/journal.pgen.1002784
Citations Scopus - 227Web of Science - 180
2012 Lim CK, Hassan KA, Tetu SG, Loper JE, Paulsen IT, 'The Effect of Iron Limitation on the Transcriptome and Proteome of Pseudomonas fluorescens Pf-5', PLOS ONE, 7 (2012) [C1]
DOI 10.1371/journal.pone.0039139
Citations Scopus - 32Web of Science - 42
2011 Ostrowski M, Tetu S, Hassan K, Penesyan A, Lim K, Elbourne L, et al., 'From omics to systems biology: Exploring the mystery box of microbial life', Microbiology Australia, 32 147-150 (2011) [C1]
2011 Mavrodi DV, Joe A, Mavrodi OV, Hassan KA, Weller DM, Paulsen IT, et al., 'Structural and Functional Analysis of the Type III Secretion System from Pseudomonas fluorescens Q8r1-96', JOURNAL OF BACTERIOLOGY, 193 177-189 (2011) [C1]
DOI 10.1128/JB.00895-10
Citations Scopus - 22Web of Science - 20
2011 Chowdhury PR, Boucher Y, Hassan KA, Paulsen IT, Stokes HW, Labbate M, 'Genome Sequence of Vibrio rotiferianus Strain DAT722', JOURNAL OF BACTERIOLOGY, 193 3381-3382 (2011) [C1]
DOI 10.1128/JB.05089-11
Citations Scopus - 10Web of Science - 7
2011 Eijkelkamp BA, Stroeher UH, Hassan KA, Papadimitrious MS, Paulsen IT, Brown MH, 'Adherence and motility characteristics of clinical Acinetobacter baumannii isolates', FEMS MICROBIOLOGY LETTERS, 323 44-51 (2011) [C1]
DOI 10.1111/j.1574-6968.2011.02362.x
Citations Scopus - 52Web of Science - 48
2011 Janto B, Ahmed A, Ito M, Liu J, Hicks DB, Pagni S, et al., 'Genome of alkaliphilic Bacillus pseudofirmus OF4 reveals adaptations that support the ability to grow in an external pH range from 7.5 to 11.4', ENVIRONMENTAL MICROBIOLOGY, 13 3289-3309 (2011) [C1]
DOI 10.1111/j.1462-2920.2011.02591.x
Citations Scopus - 31Web of Science - 27
2011 Hassan KA, Brzoska AJ, Wilson NL, Eijkelkamp BA, Brown MH, Paulsen IT, 'Roles of DHA2 Family Transporters in Drug Resistance and Iron Homeostasis in Acinetobacter spp.', JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY, 20 116-124 (2011) [C1]
DOI 10.1159/000325367
Citations Scopus - 10Web of Science - 11
2011 Eijkelkamp BA, Hassan KA, Paulsen IT, Brown MH, 'Development of a High-Throughput Cloning Strategy for Characterization of Acinetobacter baumannii Drug Transporter Proteins', JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY, 20 211-219 (2011) [C1]
DOI 10.1159/000329836
Citations Scopus - 4Web of Science - 3
2011 Eijkelkamp BA, Hassan KA, Paulsen IT, Brown MH, 'Investigation of the human pathogen Acinetobacter baumannii under iron limiting conditions', BMC GENOMICS, 12 (2011) [C1]
DOI 10.1186/1471-2164-12-126
Citations Scopus - 72Web of Science - 69
2011 Deshpande CN, Harrop SJ, Boucher Y, Hassan KA, Di Leo R, Xu X, et al., 'Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module', PLOS ONE, 6 (2011) [C1]
DOI 10.1371/journal.pone.0016934
Citations Scopus - 8Web of Science - 8
2010 Hassan KA, Baltzer S, Paulsen I, Brown M, 'Pumping out biocides¿cause for concern', Microbiology Australia, 31 178-181 (2010)
2010 Hassan KA, Johnson A, Shaffer BT, Ren Q, Kidarsa TA, Elbourne LDH, et al., 'Inactivation of the GacA response regulator in Pseudomonas fluorescens Pf-5 has far-reaching transcriptomic consequences', ENVIRONMENTAL MICROBIOLOGY, 12 899-915 (2010)
DOI 10.1111/j.1462-2920.2009.02134.x
Citations Scopus - 85Web of Science - 76
2009 Hassan KA, Xu Z, Watkins RE, Brennan RG, Skurray RA, Brown MH, 'Optimized production and analysis of the staphylococcal multidrug efflux protein QacA', PROTEIN EXPRESSION AND PURIFICATION, 64 118-124 (2009)
DOI 10.1016/j.pep.2008.11.009
Citations Scopus - 9Web of Science - 7
2009 Tsolis RM, Seshadri R, Santos RL, Sangari FJ, García Lobo JM, de Jong MF, et al., 'Genome degradation in Brucella ovis corresponds with narrowing of its host range and tissue tropism', PLoS ONE, 4 (2009)

Brucella ovis is a veterinary pathogen associated with epididymitis in sheep. Despite its genetic similarity to the zoonotic pathogens B. abortus, B. melitensis and B. suis, B. ov... [more]

Brucella ovis is a veterinary pathogen associated with epididymitis in sheep. Despite its genetic similarity to the zoonotic pathogens B. abortus, B. melitensis and B. suis, B. ovis does not cause zoonotic disease. Genomic analysis of the type strain ATCC25840 revealed a high percentage of pseudogenes and increased numbers of transposable elements compared to the zoonotic Brucella species, suggesting that genome degradation has occurred concomitant with narrowing of the host range of B. ovis. The absence of genomic island 2, encoding functions required for lipopolysaccharide biosynthesis, as well as inactivation of genes encoding urease, nutrient uptake and utilization, and outer membrane proteins may be factors contributing to the avirulence of B. ovis for humans. A 26.5 kb region of B. ovis ATCC25840 Chromosome II was absent from all the sequenced human pathogenic Brucella genomes, but was present in all of 17 B. ovis isolates tested and in three B. ceti isolates, suggesting that this DNA region may be of use for differentiating B. ovis from other Brucella spp. This is the first genomic analysis of a non-zoonotic Brucella species. The results suggest that inactivation of genes involved in nutrient acquisition and utilization, cell envelope structure and urease may have played a role in narrowing of the tissue tropism and host range of B. ovis. © 2009 Tsolis et al.

DOI 10.1371/journal.pone.0005519
Citations Scopus - 60
2008 Hassan KA, Souhani T, Skurray RA, Brown MH, 'Analysis of tryptophan residues in the staphylococcal multidrug transporter QacA reveals long-distance functional associations of residues on opposite sides of the membrane', JOURNAL OF BACTERIOLOGY, 190 2441-2449 (2008)
DOI 10.1128/JB.01864-07
Citations Scopus - 13Web of Science - 12
2008 Wu J, Hassan KA, Skurray RA, Brown MH, 'Functional analyses reveal an important role for tyrosine residues in the staphylococcal multidrug efflux protein QacA', BMC Microbiology, 8 (2008)

Background. The staphylococcal QacA multidrug efflux protein confers resistance to an exceptional number of structurally unrelated antimicrobial compounds. Aromatic amino acid res... [more]

Background. The staphylococcal QacA multidrug efflux protein confers resistance to an exceptional number of structurally unrelated antimicrobial compounds. Aromatic amino acid residues have been shown to be highly important for the transport function of several multidrug transporters and are intimately involved in multidrug binding. This study investigated the structural and functional importance of the seven tyrosine residues in QacA by examining the phenotypic effect of incorporating conservative (aromatic) and non-conservative (non-aromatic) substitutions for these residues. Results. Determination of the resistance profiles and analysis of drug transport assays revealed that non-conservative substitutions for most tyrosine residues influenced the QacA drug recognition spectrum. However, an aromatic residue at three tyrosine positions, 63, 410 and 429, was of importance for QacA-mediated transport and resistance to the majority of substrates tested. Conclusion. A tyrosine or phenylalanine residue at amino acid positions corresponding to 63 of QacA in related drug efflux proteins is found to be highly conserved. Therefore, an aromatic side chain at this position is likely to partake in a function common to these drug transporters, such as proton translocation or essential intramolecular contacts, whereas aromatic residues at the non-conserved 410 and 429 positions are expected to mediate a QacA-specific function, possibly forming or stabilising part of the QacA drug binding region. © 2008 Wu et al; licensee BioMed Central Ltd.

DOI 10.1186/1471-2180-8-147
Citations Scopus - 5Web of Science - 5
2007 Hassan KA, Skurray RA, Brown MH, 'Transmembrane helix 12 of the Staphylococcus aureus multidrug transporter QacA lines the bivalent cationic drug binding pocket', JOURNAL OF BACTERIOLOGY, 189 9131-9134 (2007)
DOI 10.1128/JB.01492-07
Citations Scopus - 10Web of Science - 9
2007 Hassan KA, Skurray RA, Brown MH, 'Active export proteins mediating drug resistance in staphylococci', JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY, 12 180-196 (2007)
DOI 10.1159/000099640
Citations Scopus - 33Web of Science - 31
2006 Hassan KA, Galea M, Wu J, Mitchell BA, Skurray RA, Brown MH, 'Functional effects of intramembranous proline substitutions in the staphylococcal multidrug transporter QacA', FEMS Microbiology Letters, 263 76-85 (2006)

The QacA multidrug transporter is encoded on Staphylococcus aureus multidrug resistance plasmids and confers broad-range antimicrobial resistance to more than 30 monovalent and bi... [more]

The QacA multidrug transporter is encoded on Staphylococcus aureus multidrug resistance plasmids and confers broad-range antimicrobial resistance to more than 30 monovalent and bivalent lipophilic, cationic compounds from at least 12 different chemical classes. QacA contains 10 proline residues predicted to be within transmembrane regions, several of which are conserved in related export proteins. Proline residues are classically known as helix-breakers and are highly represented within the transmembrane helices of membrane transport proteins, where they can mediate the formation of structures essential for protein stability and transport function. The importance of these 10 intramembranous proline residues for QacA-mediated transport function was determined by examining the functional effect of substituting these residues with glycine, alanine or serine. Several proline-substituted QacA mutants failed to confer high-level resistance to selected QacA substrates. However, no single proline mutation, including those at conserved positions, significantly disrupted QacA protein expression or QacA-mediated resistance to all representative substrates, suggesting that these residues are not essential for the formation of structures requisite to the QacA substrate transport mechanism. © 2006 Federation of European Microbiological Societies Published by Blackwell Publishing Ltd. All rights reserved.

DOI 10.1111/j.1574-6968.2006.00411.x
Citations Scopus - 17Web of Science - 16
2006 Hassan KA, Robinson KL, Smith AN, Gibson JH, Skurray RA, Brown MH, 'Glycine-rich transmembrane helix 10 in the staphylococcal tetracycline transporter TetA(K) lines a solvent-accessible channel', BIOCHEMISTRY, 45 15661-15669 (2006)
DOI 10.1021/bi0614380
Citations Scopus - 4Web of Science - 4
Show 48 more journal articles

Review (1 outputs)

Year Citation Altmetrics Link
2014 Jackson SM, Patching SG, Hassan KA, Sharples D, Paulsen IT, Hussain R, et al., 'Tackling bacterial resistance to antiseptics (2014)
Edit

Grants and Funding

Summary

Number of grants 5
Total funding $2,253,058

Click on a grant title below to expand the full details for that specific grant.


20172 grants / $1,156,058

Pacing across the membrane: Characterising the PACE family of multidrug efflux systems$640,815

Funding body: National Health and Medical Research Council

Funding body National Health and Medical Research Council
Project Team

Ian T. Paulsen, Karl A. Hassan, Peter JF. Henderson

Scheme Project Grant
Role Investigator
Funding Start 2017
Funding Finish 2020
GNo
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON N

Circuit breaker: Investigating the regulatory circuits controlling expression of drug efflux pumps in the nosocomial pathogen Acinetobacter baumannii$515,243

Funding body: National Health & Medical Research Council

Funding body National Health & Medical Research Council
Project Team

Ian T. Paulsen, Karl A. Hassan

Scheme Project Grant
Role Investigator
Funding Start 2017
Funding Finish 2019
GNo
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON N

20161 grants / $410,000

What genetic factors are involved in colonisation of plant surfaces by Pseudomonas biocontrol strains?$410,000

Funding body: ARC (Australian Research Council)

Funding body ARC (Australian Research Council)
Project Team

Ian T. Paulsen, Karl A. Hassan, Sasha G. Tetu, Joyce E. Loper

Scheme Discovery Project
Role Investigator
Funding Start 2016
Funding Finish 2018
GNo
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON N

20141 grants / $387,000

An ace up their sleeve: characterisation of a novel family of drug efflux systems represented by the Acinetobacter AceI exporter$387,000

Funding body: National Health and Medical Research Council

Funding body National Health and Medical Research Council
Project Team

Ian T. Paulsen, Karl A. Hassan, Peter JF. Henderson

Scheme Project Grant
Role Investigator
Funding Start 2014
Funding Finish 2017
GNo
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON N

20111 grants / $300,000

Commensal benefits: genomic basis for suppressing plant pathogens with Pseudomonas biocontrol species$300,000

Funding body: ARC (Australian Research Council)

Funding body ARC (Australian Research Council)
Project Team

Ian T. Paulsen, Karl A. Hassan

Scheme Discovery Project
Role Investigator
Funding Start 2011
Funding Finish 2014
GNo
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON N
Edit

Research Collaborations

The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.

Country Count of Publications
Australia 47
United States 18
United Kingdom 7
Norway 5
France 3
More...
Edit

Dr Karl Hassan

Position

Senior Lecturer
School of Environmental and Life Sciences
Faculty of Science

Contact Details

Email karl.hassan@newcastle.edu.au
Phone (02) 4921 7236

Office

Room LS-246
Building Life Sciences Building
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
Edit