ORCID Profile
0000-0002-6845-9702
Current Organisations
University of California Santa Barbara
,
Penn State
,
Tasmanian Department of Health
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Publisher: Cold Spring Harbor Laboratory
Date: 03-01-2020
DOI: 10.1101/2020.01.02.893487
Abstract: Non-typeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic respiratory tract infections, including otitis media and acute exacerbations of chronic obstructive pulmonary disease. Despite the enormous disease burden associated with NTHi infections, there are currently no effective prevention strategies, and the rapid development of antibiotic resistance is compromising treatment. We previously discovered Haemophilus haemolyticus (Hh) strains capable of producing haemophilin (HPL), a heme-binding protein that restricts NTHi growth by limiting its access to an essential growth factor, heme. Thus, these strains may have utility as a probiotic therapy against NTHi infection by limiting colonization, migration and subsequent infection in susceptible in iduals. Here, we have assessed the feasibility of this approach by in vitro competition assays between NTHi and Hh strains with varying capacity to produce HPL. HPL-producing strains of Hh exhibited enhanced growth and consistently outcompeted NTHi compared to Hh strains unable to produce the protein. This competitive advantage was maintained over a period of six days, culminating in the complete eradication of NTHi. Expression analysis of HPL during competition coincided with the NTHi-inhibitory capacity of HPL-producers, confirming that inhibition was mediated by the presence of HPL. Together, results suggest that natural levels of HPL production by Hh are sufficient to limit NTHi’s access to heme, even under excess heme conditions unlikely to be encountered in vivo. Further investigation is required to determine the protective capacity of HPL-producers in vivo and their ability to interrupt NTHi colonization of host cells.
Publisher: Oxford University Press (OUP)
Date: 22-06-2023
Abstract: We measure precise orbits and dynamical masses and derive age constraints for six confirmed and one candidate Sirius-like systems, including the Hyades member HD 27483. Our orbital analysis incorporates radial velocities, relative astrometry, and Hipparcos–Gaia astrometric accelerations. We constrain the main-sequence lifetime of a white dwarf’s progenitor from the remnant’s dynamical mass and semi-empirical initial–final mass relations and infer the cooling age from mass and effective temperature. We present new relative astrometry of HD 27483 B from Keck/NIRC2 observations and archival Hubble Space Telescope data, and obtain the first dynamical mass of ${0.798}_{-0.041}^{+0.10}$ M⊙, and an age of ${450}_{-180}^{+570}$ Myr, consistent with previous age estimates of Hyades. We also measure precise dynamical masses for HD 114174 B (0.591 ± 0.011 M⊙) and HD 169889 B (${0.526}_{-0.037}^{+0.039}$ M⊙), but their age precisions are limited by their uncertain temperatures. For HD 27786 B, the unusually small mass of 0.443 ± 0.012 M⊙ suggests a history of rapid mass-loss, possibly due to binary interaction in its progenitor’s asymtotic giant branch phase. The orbits of HD 118475 and HD 136138 from our radial velocity fitting are overall in good agreement with Gaia DR3 astrometric two-body solutions, despite moderate differences in the eccentricity and period of HD 136138. The mass of ${0.580}_{-0.039}^{+0.052}$ M⊙ for HD 118475 B and a speckle imaging non-detection confirms that the companion is a white dwarf. Our analysis shows ex les of a rich number of precise WD dynamical mass measurements enabled by Gaia DR3 and later releases, which will improve empirical calibrations of the white dwarf initial–final mass relation.
Publisher: MDPI AG
Date: 10-05-2021
DOI: 10.3390/PATHOGENS10050577
Abstract: Nontypeable Haemophilus influenzae (NTHi) is a major respiratory pathogen that initiates infection by colonising the upper airways. Strategies that interfere with this interaction may therefore have a clinically significant impact on the ability of NTHi to cause disease. We have previously shown that strains of the commensal bacterium Haemophilus haemolyticus (Hh) that produce a novel haem-binding protein, haemophilin, can prevent NTHi growth and interactions with host cells in vitro. We hypothesized that natural pharyngeal carriage of Hh strains with the hpl open reading frame (Hh-hpl+) would be associated with a lower prevalence and/or density of NTHi colonisation in healthy in iduals. Oropharyngeal swabs were collected from 257 healthy adults in Australia between 2018 and 2019. Real-time PCR was used to quantitatively compare the oropharyngeal carriage load of NTHi and Hh populations with the Hh-hpl+ or Hh-hpl− genotype. The likelihood of acquiring/maintaining NTHi colonisation status over a two- to six-month period was assessed in in iduals that carried either Hh-hpl− (n = 25) or Hh-hpl+ (n = 25). Compared to carriage of Hh-hpl− strains, adult (18–65 years) and elderly ( years) participants that were colonised with Hh-hpl+ were 2.43 or 2.67 times less likely to carry NTHi in their oropharynx, respectively. Colonisation with high densities of Hh-hpl+ correlated with a low NTHi carriage load and a 2.63 times lower likelihood of acquiring/maintaining NTHi colonisation status between visits. Together with supporting in vitro studies, these results encourage further investigation into the potential use of Hh-hpl+ as a respiratory probiotic candidate for the prevention of NTHi infection.
Publisher: Portland Press Ltd.
Date: 07-2019
DOI: 10.1042/CS20181009
Abstract: Chronic respiratory diseases are among the leading causes of mortality worldwide, with the major contributor, chronic obstructive pulmonary disease (COPD) accounting for approximately 3 million deaths annually. Frequent acute exacerbations (AEs) of COPD (AECOPD) drive clinical and functional decline in COPD and are associated with accelerated loss of lung function, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEs and consequently constitute a significant comorbidity in COPD. However, current pharmacological interventions are ineffective in preventing infectious exacerbations and their treatment is compromised by the rapid development of antibiotic resistance. Thus, alternative preventative therapies need to be considered. Pathogen adherence to the pulmonary epithelium through host receptors is the prerequisite step for invasion and subsequent infection of surrounding structures. Thus, disruption of bacterial–host cell interactions with receptor antagonists or modulation of the ensuing inflammatory profile present attractive avenues for therapeutic development. This review explores key mediators of pathogen–host interactions that may offer new therapeutic targets with the potential to prevent viral/bacterial-mediated AECOPD. There are several conceptual and methodological hurdles h ering the development of new therapies that require further research and resolution.
Publisher: MDPI AG
Date: 25-03-2020
Abstract: Nontypeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic respiratory tract infections. However, there are currently no effective vaccination strategies, and existing treatments are compromised by antibiotic resistance. We previously characterized Haemophilus haemolyticus (Hh) strains capable of producing haemophilin (HPL), a heme-binding protein that restricts NTHi growth by limiting its access to an essential growth factor, heme. Thus, these strains may have utility as a probiotic therapy against NTHi infection by limiting colonization, migration and subsequent infection in susceptible in iduals. Here, we assess the preliminary feasibility of this approach by direct in vitro competition assays between NTHi and Hh strains with varying capacity to produce HPL. Subsequent changes in NTHi growth rate and fitness, in conjunction with HPL expression analysis, were employed to assess the NTHi-inhibitory capacity of Hh strains. HPL-producing strains of Hh not only outcompeted NTHi during short-term and extended co-culture, but also demonstrated a growth advantage compared with Hh strains unable to produce the protein. Additionally, HPL expression levels during competition correlated with the NTHi-inhibitory phenotype. HPL-producing strains of Hh demonstrate significant probiotic potential against NTHi colonization in the upper respiratory tract, however, further investigations are warranted to demonstrate a range of other characteristics that would support the eventual development of a probiotic.
Publisher: CSIRO Publishing
Date: 06-09-2021
DOI: 10.1071/MA21032
Abstract: Over the past decade, nontypeable Haemophilus influenzae (NTHi) has gained recognition as a major opportunistic pathogen of the respiratory tract that imposes a substantial global burden of disease, owing to a high rate of morbidity and ensuing complications. Further lifying the global impact of NTHi infections is the increasing spectrum and prevalence of antibiotic resistance, leading to higher rates of treatment failure with first- and second-line antibiotics regimes. The threat of antibiotic resistance was recognised by the World Health Organization in 2017, listing NTHi as a priority pathogen for which new therapies are urgently needed. Despite significant efforts, there are currently no effective vaccine strategies available that can slow the growing burden of NTHi disease. Consequently, alternative preventative or therapeutic approaches that do not rely on antibiotic susceptibility or stable vaccine targets are becoming more attractive. The nutritional dependency for haem at all stages of NTHi pathogenesis exposes a vulnerability that may be exploited for the development of such therapies. This article will discuss the therapeutic potential of strategies that limit NTHi access to this vital nutrient, with particular focus on a novel bacteriotherapeutic approach under development.
Publisher: MDPI AG
Date: 2021
DOI: 10.3390/PATHOGENS10010029
Abstract: Nontypeable Haemophilus influenzae (NTHi) is a significant respiratory tract pathogen responsible for infections that collectively pose a substantial health and socioeconomic burden. The clinical course of these infections is largely dictated by NTHi interactions with host respiratory epithelia, and thus, approaches that disrupt colonisation and invasion may have significant therapeutic potential. Survival, successful host–cell interactions, and pathogenesis are reliant on NTHi’s ability to sequester host-derived haem. Previously, we demonstrated the therapeutic potential of exploiting this haem-dependence using a closely related competitor bacterium, Haemophilus haemolyticus (Hh). Hh strains capable of producing the novel haem-binding protein haemophilin (Hpl) possessed potent inhibitory activity by restricting NTHi access to haem in a broth co-culture environment. Here, we extend this work to cell culture models that more closely represent the human respiratory epithelium and show that Hh strains with high levels of hpl expression protect epithelial cell line monolayers against adhesion and invasion by NTHi. Inhibitory activity was dependent on the level of Hpl production, which was stimulated by NTHi challenge and nasopharyngeal cell exposure. Provided these protective benefits translate to in vivo applications, Hpl-producing Hh may have probiotic utility against NTHi infections by inhibiting requisite nasopharyngeal colonisation.
Publisher: American Astronomical Society
Date: 12-10-2022
Abstract: Gliese 86 is a nearby K dwarf hosting a giant planet on a ≈16 day orbit and an outer white dwarf companion on a ≈century-long orbit. In this study we combine radial velocity data (including new measurements spanning more than a decade) with high angular resolution imaging and absolute astrometry from Hipparcos and Gaia to measure the current orbits and masses of both companions. We then simulate the evolution of the Gl 86 system to constrain its primordial orbit when both stars were on the main sequence the closest approach between the two stars was then about 9 au. Such a close separation limited the size of the protoplanetary disk of Gl 86 A and dynamically hindered the formation of the giant planet around it. Our measurements of Gl 86 B and Gl 86 Ab’s orbits reveal Gl 86 as a system in which giant planet formation took place in a disk truncated at ≈2 au. Such a disk would be just big enough to harbor the dust mass and total mass needed to assemble Gl 86 Ab’s core and envelope, assuming a high disk accretion rate and a low viscosity. Inefficient accretion of the disk onto Gl 86 Ab, however, would require a disk massive enough to approach the Toomre stability limit at its outer truncation radius. The orbital architecture of the Gl 86 system shows that giant planets can form even in severely truncated disks and provides an important benchmark for planet formation theory.
Publisher: SPIE
Date: 09-08-2016
DOI: 10.1117/12.2233443
Location: United States of America
Start Date: 2019
End Date: 2021
Funder: Clifford Craig Foundation
View Funded ActivityStart Date: 2017
End Date: 2021
Funder: University of Tasmania
View Funded Activity