Yue Qu
Monash University, Microbiology, Adjunct
Ventricular assist device (VAD)-specific infections, in particular, driveline infections, are a concerning complication of VAD implantation that often results in significant morbidity and even mortality. The presence of a percutaneous... more
Ventricular assist device (VAD)-specific infections, in particular, driveline infections, are a concerning complication of VAD implantation that often results in significant morbidity and even mortality. The presence of a percutaneous driveline at the skin exit-site and in the subcutaneous tunnel allows biofilm formation and migration by many bacterial and fungal pathogens. Biofilm formation is an important microbial strategy, providing a shield against antimicrobial treatment and human immune responses; biofilm migration facilitates the extension of infection to deeper tissues such as the pump pocket and the bloodstream. Despite the introduction of multiple preventative strategies, driveline infections still occur with a high prevalence of ~10–20% per year and their treatment outcomes are frequently unsatisfactory. Clinical diagnosis, prevention and management of driveline infections are being targeted to specific microbial pathogens grown as biofilms at the driveline exit-site or ...
Research Interests:
Research Interests:
Research Interests: Engineering, Chemistry, Medicine, Biological Sciences, Humans, and 12 moreCandida albicans, Staphylococcus epidermidis, CHEMICAL SCIENCES, Anti-Bacterial Agents, Antifungal Agents, Microbial Sensitivity Tests, Guanidines, Structure activity Relationship, Erythrocytes, Biomacromolecules, Molecular Structure, and Hemolysis
Research Interests:
Macromolecular entities, such as polymers, peptides, proteins, and hybrid materials thereof, are herein reviewed as promising antibiofilm agents.
Research Interests:
Background Pre-administration of probiotic Lactobacilli attenuates ethanol-induced gastric mucosal injury (GMI). The underpinning mechanisms remain to be elucidated. We speculated that lactate, the main metabolite of Lactobacillus that... more
Background Pre-administration of probiotic Lactobacilli attenuates ethanol-induced gastric mucosal injury (GMI). The underpinning mechanisms remain to be elucidated. We speculated that lactate, the main metabolite of Lactobacillus that can be safely used as a common food additive, mediated the gastroprotective effect. This study aimed to gain experimental evidence to support our hypothesis and to shed lights on its underlying mechanisms. Methods Lactate was orally administrated to mice at different doses 30 min prior to the induction of GMI. Gastric tissue samples were collected and underwent histopathological and immunohistochemical assessments, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction (qPCR) and western blot analyses. Results Pretreatment with lactate at 1–3 g/kg significantly curtailed the severity of ethanol-induced GMI, as shown by morphological and histopathological examinations of gastric tissue samples. Significantly lower level of cytokines ...
Research Interests:
Background Pre-administration of probiotic Lactobacilli attenuates ethanol-induced gastric mucosal injury (GMI). The underpinning mechanisms remain to be elucidated. We speculated that lactate, the main metabolite of Lactobacillus that... more
Background Pre-administration of probiotic Lactobacilli attenuates ethanol-induced gastric mucosal injury (GMI). The underpinning mechanisms remain to be elucidated. We speculated that lactate, the main metabolite of Lactobacillus that can be safely used as a common food additive, mediated the gastroprotective effect. This study aimed to gain experimental evidence to support our hypothesis and to shed lights on its underlying mechanisms. Methods Lactate was orally administrated to mice at different doses 30 min prior to the induction of GMI. Gastric tissue samples were collected and underwent histopathological and immunohistochemical assessments, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction (qPCR) and western blot analyses. Results Pretreatment with lactate at 1–3 g/kg significantly curtailed the severity of ethanol-induced GMI, as shown by morphological and histopathological examinations of gastric tissue samples. Significantly lower level of cytokines ...
Research Interests:
Research Interests:
Objectives: In adult ventricular assist device (VAD) programs in Australian hospitals, Medihoney Antibacterial Wound Gel (MAWG) is routinely used at the skin exit-site of VAD drivelines to prevent infections; however, its effectiveness... more
Objectives: In adult ventricular assist device (VAD) programs in Australian hospitals, Medihoney Antibacterial Wound Gel (MAWG) is routinely used at the skin exit-site of VAD drivelines to prevent infections; however, its effectiveness remains unclear. Our aim was to assess antimicrobial activity of Medihoney wound gel, using in vitro models that mimic clinical biofilms grown at the driveline exit-site.Methods: Antimicrobial susceptibility testing of MAWG was performed for 24 clinical isolates grown under planktonic conditions, and four representative strains grown as biofilms. Different antimicrobial mechanisms of MAWG were assessed respectively for their relative contribution to its anti-biofilm activity. A colony biofilm assay and a drip-flow biofilm reactor assay mimicking the driveline exit-site environment were used to evaluate the activity of MAWG against biofilm growth at the driveline exit-site.Results: MAWG demonstrated species-specific activity against planktonic cultures...
Research Interests:
Research Interests:
OBJECTIVES Driveline infections remain an important complication of ventricular assist device therapy, with biofilm formation being a major contributor. This study aimed to elucidate factors that govern biofilm formation and migration on... more
OBJECTIVES Driveline infections remain an important complication of ventricular assist device therapy, with biofilm formation being a major contributor. This study aimed to elucidate factors that govern biofilm formation and migration on clinically relevant ventricular assist device drivelines. METHODS Experimental analyses were performed on HeartWare HVAD (HeartWare International Inc, Framingham, Mass) drivelines to assess surface chemistry and biofilm formation. To mimic the driveline exit site, a drip-flow biofilm reactor assay was used. To mimic a subcutaneous tissue environment, a tunnel-based interstitial biofilm assay was developed. Clinical HVAD drivelines explanted at the time of cardiac transplantation were also examined by scanning electron microscopy. RESULTS Common causative pathogens of driveline infections were able to adhere to the smooth and velour sections of the HVAD driveline and formed robust biofilms in the drip-flow biofilm reactor; however, Pseudomonas aeruginosa and Candida albicans had greater biomass. Biofilm migration within the interstitial driveline tunnel was evident for Staphylococcus epidermidis, Staphylococcus aureus, and C albicans, but not P aeruginosa. Biofilm formation by staphylococci was 500 to 10,000 times higher in the tunnel-based model compared with our exit site model. The 3-dimensional structure of the driveline velour and the use of silicone adhesive in driveline manufacturing were found to promote biofilm growth, and explanted patient drivelines demonstrated inadequate tissue in-growth along the entire velour with micro-gaps between velour fibers. CONCLUSIONS This work highlights the predilection of pathogens to different parts of the driveline, the importance of the subcutaneous tunnel to biofilm formation and migration, and the presence of micro-gaps in clinical drivelines that could facilitate invasive driveline infections.
Research Interests:
The Xpert MTB/RIF is recommended by the World Health Organization as a first line rapid test for the diagnosis of pulmonary tuberculosis (TB); however, China does not routinely use this test, partially due to the lack of a sufficient... more
The Xpert MTB/RIF is recommended by the World Health Organization as a first line rapid test for the diagnosis of pulmonary tuberculosis (TB); however, China does not routinely use this test, partially due to the lack of a sufficient number of systematic evaluations of this assay in local patients. The aims of this study were to comprehensively assess the diagnostic performance of Xpert MTB/RIF, either alone or in combination with conventional assays for the diagnosis of pulmonary TB in adult Chinese patients. Xpert MTB/RIF tests were performed in 190 adult patients with suspected pulmonary TB, using bronchoalveolar lavage fluid (BALF) as test specimens. In parallel, conventional tests were carried out using the same BALF samples. Using two different reference standards, the performance of Xpert MTB/RIF, conventional assays and their combinations were evaluated. Using mycobacterial culture as the reference comparator, Xpert MTB/RIF was found to be superior to smear-microscopy in det...
Research Interests:
An article by Buhmann et al. highlights the importance of integrating clinically relevant factors into in vitro biofilm models to predict the in vivo performance of anti-infective medical devices [1]. Biofilm formation is an important... more
An article by Buhmann et al. highlights the importance of integrating clinically relevant factors into in vitro biofilm models to predict the in vivo performance of anti-infective medical devices [1]. Biofilm formation is an important strategy for microorganisms in the pathogenesis of device-associated hospital-acquired infections (DA-HAIs) as it provides a shield against antimicrobial agents and human immune responses. While a broad range of anti-infective strategies have been developed for use on medical devices, the combination of multiple strategies, such as nonadhesive and antimicrobial coatings, has been considered only recently as an effective route to the prevention of biofilm-related DA-HAIs [2].
Research Interests:
Research Interests:
Inspired by the interesting natural antimicrobial properties of honey, biohybrid composite materials containing a low-fouling polymer hydrogel network and an encapsulated antimicrobial peroxide-producing enzyme have been developed. These... more
Inspired by the interesting natural antimicrobial properties of honey, biohybrid composite materials containing a low-fouling polymer hydrogel network and an encapsulated antimicrobial peroxide-producing enzyme have been developed. These synergistically combine both passive and active mechanisms for reducing microbial bacterial colonization. The mechanical properties of these materials were assessed using compressive mechanical analysis, which revealed these hydrogels possessed tunable mechanical properties with Young’s moduli ranging from 5 to 500 kPa. The long-term enzymatic activities of these materials were also assessed over a 1-month period using colorimetric assays. Finally, the passive low-fouling properties and active antimicrobial activity against a leading opportunistic pathogen, Staphylococcus epidermidis, were confirmed using bacterial cell counting and bacterial adhesion assays. This study resulted in non-adhesive substrate-permeable antimicrobial materials, which coul...
Recent studies indicate that mitochondrial functions impinge on cell wall integrity, drug tolerance, and virulence of human fungal pathogens. However, the mechanistic aspects of these processes are poorly understood. We focused on the... more
Recent studies indicate that mitochondrial functions impinge on cell wall integrity, drug tolerance, and virulence of human fungal pathogens. However, the mechanistic aspects of these processes are poorly understood. We focused on the mitochondrial outer membrane SAM ( S orting and A ssembly M achinery) complex subunit Sam37 in Candida albicans . Inactivation of SAM37 in C. albicans leads to a large reduction in fitness, a phenotype not conserved with the model yeast Saccharomyces cerevisiae . Our data indicate that slow growth of the sam37ΔΔ mutant results from mitochondrial DNA loss, a new function for Sam37 in C. albicans , and from reduced activity of the essential SAM complex subunit Sam35. The sam37ΔΔ mutant was hypersensitive to drugs that target the cell wall and displayed altered cell wall structure, supporting a role for Sam37 in cell wall integrity in C. albicans . The sensitivity of the mutant to membrane-targeting antifungals was not significantly altered. The sam37ΔΔ m...
Research Interests:
Research Interests: Microbiology, Biofilms, Medical Microbiology, Transcription Factors, Adhesion, and 18 moreExtracellular Matrix, Antibiotic Resistance, Growth, In Vitro, Humans, Biofilm, Biopolymers, Resistance, Cell, Bacteria, Antimicrobial chemotherapy, Staphylococcus epidermidis, Anti-Bacterial Agents, Microbial Sensitivity Tests, Monolayer, Microbial Viability, Bacterial Adhesion, and Persister Cells
Biofilm-related human infections have high mortality rates due to drug resistance. Cohabitation of diverse microbes in polymicrobial biofilms is common and these infections present additional challenges for treatment compared with... more
Biofilm-related human infections have high mortality rates due to drug resistance. Cohabitation of diverse microbes in polymicrobial biofilms is common and these infections present additional challenges for treatment compared with monomicrobial biofilms. Here, we address this therapeutic gap by assessing the potential of a new class of antimicrobial agents, guanylated polymethacrylates, in the treatment of polymicrobial biofilms built by two prominent human pathogens, the fungus Candida albicans and the bacterium Staphylococcus aureus. We used imaging and quantitative methods to test the antibiofilm efficacy of guanylated polymethacrylates, a new class of drugs that structurally mimic antimicrobial peptides. We further compared guanylated polymethacrylates with first-line antistaphylococcal and anti-Candida agents used as combinatorial therapy against polymicrobial biofilms. Guanylated polymethacrylates were highly effective as a sole agent, killing both C. albicans and S. aureus wh...
Research Interests:
Biofilm formation is a major pathogenicity strategy of Staphylococcus epidermidis causing various medical-device infections. Persister cells have been implicated in treatment failure of such infections. We sought to profile bacterial... more
Biofilm formation is a major pathogenicity strategy of Staphylococcus epidermidis causing various medical-device infections. Persister cells have been implicated in treatment failure of such infections. We sought to profile bacterial subpopulations residing in S. epidermidis biofilms, and to establish persister-targeting treatment strategies to eradicate biofilms. Population analysis was performed by challenging single biofilm cells with antibiotics at increasing concentrations ranging from planktonic minimum bactericidal concentrations (MBCs) to biofilm MBCs (MBCbiofilm). Two populations of "persister cells" were observed: bacteria that survived antibiotics at MBCbiofilm for 24/48 hours were referred to as dormant cells; those selected with antibiotics at 8 X MICs for 3 hours (excluding dormant cells) were defined as tolerant-but-killable (TBK) cells. Antibiotic regimens targeting dormant cells were tested in vitro for their efficacies in eradicating persister cells and intact biofilms. This study confirmed that there are at least three subpopulations within a S. epidermidis biofilm: normal cells, dormant cells, and TBK cells. Biofilms comprise more TBK cells and dormant cells than their log-planktonic counterparts. Using antibiotic regimens targeting dormant cells, i.e. effective antibiotics at MBCbiofilm for an extended period, might eradicate S. epidermidis biofilms. Potential uses for this strategy are in antibiotic lock techniques and inhaled aerosolized antibiotics.
Research Interests:
The yeast Candida albicans is a human commensal and opportunistic pathogen. Although both commensalism and pathogenesis depend on metabolic adaptation, the regulatory pathways that mediate metabolic processes in C. albicans are... more
The yeast Candida albicans is a human commensal and opportunistic pathogen. Although both commensalism and pathogenesis depend on metabolic adaptation, the regulatory pathways that mediate metabolic processes in C. albicans are incompletely defined. For example, metabolic change is a major feature that distinguishes community growth of C. albicans in biofilms compared to suspension cultures, but how metabolic adaptation is functionally interfaced with the structural and gene regulatory changes that drive biofilm maturation remains to be fully understood. We show here that the RNA binding protein Puf3 regulates a posttranscriptional mRNA network in C. albicans that impacts on mitochondrial biogenesis, and provide the first functional data suggesting evolutionary rewiring of posttranscriptional gene regulation between the model yeast Saccharomyces cerevisiae and C. albicans. A proportion of the Puf3 mRNA network is differentially expressed in biofilms, and by using a mutant in the mRN...
Research Interests:
Sirtuins are an ancient family of NAD(+)-dependent deacylases connected with the regulation of fundamental cellular processes including metabolic homeostasis and genome integrity. We show the existence of a hitherto unrecognized class of... more
Sirtuins are an ancient family of NAD(+)-dependent deacylases connected with the regulation of fundamental cellular processes including metabolic homeostasis and genome integrity. We show the existence of a hitherto unrecognized class of sirtuins, found predominantly in microbial pathogens. In contrast to earlier described classes, these sirtuins exhibit robust protein ADP-ribosylation activity. In our model organisms, Staphylococcus aureus and Streptococcus pyogenes, the activity is dependent on prior lipoylation of the target protein and can be reversed by a sirtuin-associated macrodomain protein. Together, our data describe a sirtuin-dependent reversible protein ADP-ribosylation system and establish a crosstalk between lipoylation and mono-ADP-ribosylation. We propose that these posttranslational modifications modulate microbial virulence by regulating the response to host-derived reactive oxygen species.
Research Interests:
Axons act like cables, electrically wiring the nervous system. Polar bundles of microtubules (MTs) form their backbones and drive their growth. Plus-end tracking proteins (+TIPs) regulate MT growth dynamics and directionality at their... more
Axons act like cables, electrically wiring the nervous system. Polar bundles of microtubules (MTs) form their backbones and drive their growth. Plus-end tracking proteins (+TIPs) regulate MT growth dynamics and directionality at their plus ends. However, current knowledge about +TIP functions, mostly derived from work in vitro and in non-neuronal cells, may not necessarily apply to the very different context of axonal MTs. For example, the CLIP family of +TIPs are known MT polymerization promoters in non-neuronal cells. However, we show here that neither Drosophila CLIP-190 nor mammalian CLIP-170 are prominent MT plus end trackers in neurons, which we propose is due to low plus end affinity of the CAP-Gly domain-containing N-terminus and intramolecular inhibition through the C-terminus. Instead, both CLIP-190 and CLIP-170 form F-actin-dependent patches in growth cones, mediated by binding of the coiled-coil domain to Myosin-VI. Since our loss-of-function analyses in vivo and in cult...
Research Interests:
The identification of genes that improve the salt tolerance of crops is essential for the effective utilization of saline soils for agriculture. Here, we use fine mapping in a soybean (Glycine max (L.) Merr.) population derived from the... more
The identification of genes that improve the salt tolerance of crops is essential for the effective utilization of saline soils for agriculture. Here, we use fine mapping in a soybean (Glycine max (L.) Merr.) population derived from the commercial cultivars Tiefeng 8 and 85-140 to identify GmSALT3 (salt tolerance-associated gene on chromosome 3), a dominant gene associated with limiting the accumulation of sodium ions (Na+) in shoots and a substantial enhancement in salt tolerance in soybean. GmSALT3 encodes a protein from the cation/H+ exchanger family that we localized to the endoplasmic reticulum and which is preferentially expressed in the salt-tolerant parent Tiefeng 8 within root cells associated with phloem and xylem. We identified in the salt-sensitive parent, 85-140, a 3.78-kb copia retrotransposon insertion in exon 3 of Gmsalt3 that truncates the transcript. By sequencing 31 soybean landraces and 22 wild soybean (Glycine soja) a total of nine haplotypes including two salt-...
Research Interests:
The genetic study of mycobacteria, such as Mycobacterium tuberculosis and Mycobacterium ulcerans, is hampered heavily by their slow growth. We have developed efficient, versatile, and improved genetic tools for constructing unmarked... more
The genetic study of mycobacteria, such as Mycobacterium tuberculosis and Mycobacterium ulcerans, is hampered heavily by their slow growth. We have developed efficient, versatile, and improved genetic tools for constructing unmarked recombinant mycobacteria more rapidly including generating multiple mutants using the same antibiotic marker in both fast- and slow-growing mycobacteria.
Research Interests:
Antimicrobial polymers as mimics of natural antimicrobial peptides are emerging as an alternative to classic antibiotics due to their potency, selectivity and lower susceptibility to resistance. The key chemical aspects necessary to... more
Antimicrobial polymers as mimics of natural antimicrobial peptides are emerging as an alternative to classic antibiotics due to their potency, selectivity and lower susceptibility to resistance. The key chemical aspects necessary to confer high activity and selectivity to the polymer chain composition are largely known. However, little attention has been paid to how end-groups affect the overall biological activity. Here we report the use of RAFT polymerization to obtain eight well-defined cationic methacrylate polymers which bear either amine (PA1–4) or guanidine (PG1–4) pendant groups, while systematically varying the R- and Z-RAFT end-groups. These polymers were assessed in haemotoxicity assays as well as antimicrobial testing against clinically relevant pathogens; such as a vigorously biofilm forming strain of Staphylococcus epidermidis (S. epidermidis) and a vancomycin and methicillin resistant strain of Staphylococcus aureus (VISA) as well as the opportunistic fungus Candida albicans (C. albicans). The R-group was found to dominate the measured toxicity of polymers. Replacement of the anionic cyanovaleric acid R-group (PA1) with the neutral isobutyronitrile (PA3) led to over a 20 fold increase in the haemolytic activity of the polymers. The Z-group, however, was found to have more influence on the antimicrobial activity of the polymers against both VISA and C. albicans, whereby polymers with a long, lipophilic dodecylsulfanyl Z-group (PA1) were found to be more potent than those with either an ethylsulfanyl or no ZCS2-group. These results indicate that chemical control over the end-groups is a key element for achieving the desired high biological activity and selectivity, particularly when low molecular weights are required for maximum antibacterial activity.
Research Interests:
In order to colonize abiotic surfaces, bacteria and fungi undergo a profound change in their biology to form biofilms: communities of microbes embedded into a matrix of secreted macromolecules. Despite strict hygiene standards,... more
In order to colonize abiotic surfaces, bacteria and fungi undergo a profound change in their biology to form biofilms: communities of microbes embedded into a matrix of secreted macromolecules. Despite strict hygiene standards, biofilm-related infections associated with implantable devices remain a common complication in the clinic. Here, the application of highly dosed antibiotics is problematic in that the biofilm (i) provides a protective environment for microbes to evade antibiotics and/or (ii) can provide selective pressure for the evolution of antibiotic-resistant microbes. However, recent research suggests that effective prevention of biofilm formation may be achieved by multifunctional surface coatings that provide both non-adhesive and antimicrobial properties imparted by antimicrobial peptides. Such coatings are the subject of this review.
Research Interests:
Research Interests: Computational Biology, Mitochondria, Multidisciplinary, Saccharomyces cerevisiae, Phylogeny, and 9 moreMarkov chains, Cluster Analysis, Candida albicans, Biological evolution, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis, Species Specificity, Oxygen Consumption, Protein Transport, and Mitochondrial Proteins
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Microbiology, Biofilms, Medical Microbiology, Transcription Factors, Adhesion, and 18 moreExtracellular Matrix, Antibiotic Resistance, Growth, In Vitro, Humans, Biofilm, Biopolymers, Resistance, Cell, Bacteria, Antimicrobial chemotherapy, Staphylococcus epidermidis, Anti-Bacterial Agents, Microbial Sensitivity Tests, Monolayer, Microbial Viability, Bacterial Adhesion, and Persister Cells
Research Interests:
This work reports the self-assembly of a sparingly soluble antibiotic (ciprofloxacin) and a hydrophobic tripeptide ((D)Leu-Phe-Phe) into supramolecular nanostructures that yield a macroscopic hydrogel at physiological pH. Drug... more
This work reports the self-assembly of a sparingly soluble antibiotic (ciprofloxacin) and a hydrophobic tripeptide ((D)Leu-Phe-Phe) into supramolecular nanostructures that yield a macroscopic hydrogel at physiological pH. Drug incorporation results in modified morphology and rheological properties of the self-assembled hydrogel. These changes can be correlated with intermolecular interactions between the drug and the peptide, as confirmed by spectroscopic analysis (fluorescence, circular dichroism, IR). The drug appears bound within the hydrogel by non-covalent interactions, and retains its activity over a prolonged release timescale. Antimicrobial activity of the ciprofloxacin-peptide self-assembled hydrogel was evaluated against Staphylococcus aureus, Escherichia coli, and a clinical strain of Klebsiella pneumoniae. Interestingly, the peptide hydrogel alone exhibited a mild anti-bacterial activity against Gram-negative bacteria. While toxic to bacteria, no major cytotoxicity was seen in haemolysis assays of human red blood cells or in mouse fibroblast cell cultures. This new approach of drug incorporation into the nanostructure of a simple tripeptide hydrogel by self-assembly may have important applications for cost-effective wound dressings and novel antimicrobial formulations.