At the One Health Phage and Antimicrobial Resistance Laboratory (OHPAL) we investigate the interactions between bacterial pathogens and diverse antimicrobials including bacteriophages to improve therapeutic strategies for better health outcomes for animals and humans.
Antimicrobial resistance (AMR)Â develops and rapidly spreads in all settings due to antimicrobial use, making traditional antimicrobials less effective, thus threatening human and animal health, food production, and the environment.
Failure of antimicrobial therapy in human infections is projected to lead to more than 10 million deaths per year by 2050. AMR is a problem that requires coordinated action across all sectors (One Health approach) where antimicrobials are used.
The OHAPL aims to contribute to a better understanding of AMR, particularly the role of mobile genetic elements in AMR transmission across veterinary and human settings, and to the development of novel, ecological antimicrobial approaches.
Our work focuses on primary pathogens, mainly emerging opportunistic species (StaphylococcusÌý²õ±è±è,ÌýEscherichia coli,Ìý°±ô±ð²ú²õ¾±±ð±ô±ô²¹Ìýspp.,ÌýVibrio spp.), emerging virulent subtypes (ExPEC, AIEC, UPEC), virulent Rhodococcus equi, non-typhoidal Salmonella). By collating and curating diverse banks of bacteria and bacteriophages, we are also striving to develop and test novel phage-based antibacterials as alternatives or adjuncts to traditional therapies.
Our research addresses the global critical challenge of AMR, focusing on AMR mechanisms, bacterial adaptation under selective pressure, and developing novel antibacterial interventions, with real-world impact for sustainable food production and better health outcomes for all.
Our projects are funded by the NHMRC, Sydney Infectious Diseases Institute (Sydney ID), Australian Companion Animal Health Foundation, Canine Research Foundation, DAAD, Morris Animal Foundation and Sydney School of Veterinary Science Bequests. In Sydney ID, OHPAL contributes to the AMR and novel therapies theme.
This research area defines the molecular mechanisms allowing bacteria to evade antimicrobials and phages (their natural viral predators).
Key researchers: ¶Ù°ùÌýCarola Venturini, Professor , ¶Ù°ùÌýAlicia Fajardo Lubian
Bacteriophages are natural predators of bacteria that can be safely used to treat serious multidrug resistant infections when antibiotics fail. This project aims at identifying the molecular mechanisms that lead to bacterial resistance to phage attack and reduced clearance during therapy, to define key requirements for selection of bacteriophages for successful treatment of life-threatening multidrug resistant infections caused by the high priority pathogen Klebsiella pneumoniae.
Key researchers: ¶Ù°ùÌýVictoria Brookes,Ìý¶Ù°ùÌýCarola Venturini
Animal carcasses represent a critical but underexplored interface for infectious disease surveillance, particularly in low- and middle-income countries like India. This pilot project investigates livestock and wildlife carcasses in urban and rural Karnataka (India) to address gaps in zoonotic pathogen detection, antimicrobial resistance mapping, and necrobiome dynamics, exploring the feasibility of using carcasses for infectious disease surveillance and using metagenomics to characterise carcass-associated microbial communities.
Key researchers:Ìý¶Ù°ùÌýKate Worthing,Ìý¶Ù°ùÌýCarola Venturini,ÌýAssociate Professor Mary Thompson
This project aims to use phenotypic antimicrobial susceptibility testing, whole genome sequencing and bioinformatic analysis to elucidate within-host evolutionary signatures in a collection of longitudinally collected Escherichia coli and methicillin resistant Staphylococcus pseudintermedius isolates from dogs and cats with persistent infections.
Key researchers:Ìý¶Ù°ùÌýCarola Venturini,ÌýProfessorÂ
This joint Australian-German project focuses on the study of outer membrane vesicles (OMVs) from non-typhoidal Salmonella (NTS) and how these may impact antimicrobial therapy against this top-priority pathogen, main contributor to food-borne disease worldwide. Antibiotics are not commonly used in the treatment of salmonellosis. Phages natural predators of bacteria could provide a solution. However, bacteria can produce OMVs that can hinder bacterial killing by phages. This work will generate important data on bacterial phage-defence mechanisms to better develop phage-based applications against these pathogens.
This research area focuses on antimicrobial solutions for skin infections, gut dysbiosis, and recurrent urinary tract infections.
Key researchers: ¶Ù°ùÌýKate Worthing,Ìý¶Ù°ùÌýCarola Venturini,Ìý¶Ù°ùÌý, Associate Professor Mary Thompson
±«°ù´Ç±è²¹³Ù³ó´Ç²µ±ð²Ô¾±³¦ÌýEscherichia coli (UPEC) is the most common causative agent of feline urinary tract infections (UTI). UTIs are the most common reason for antimicrobial use in cats, but rising antimicrobial resistance rates mean that some UTIs in cats are increasingly difficult to treat. Even in the absence of antimicrobial resistance, treatment of UPEC can be hindered by biofilm formation. This pilot study aims to optimise a model for E. coli biofilm production on catheters in feline urine and then test the activity of a bacteriophage cocktail and antimicrobial peptides against feline UPEC and their biofilms.
Key researchers:Ìý¶Ù°ùÌýCarola Venturini, ¶Ù°ùÌýKate Worthing,ÌýProfessor Kim Chan,Ìý
The aetiological agents of hard-to-treat multidrug resistant (MDR) infections in dogs comprise both Gram-negative (e.g. Enterobacterales, particularly MDR Escherichia coli) and Gram-positive species (e.g. methicillin resistant Staphylococcus pseudintermedius or MRSP). This project will test phages with the best therapeutic potential against these primary pathogens, singly and in combination, in hydrogel, spray, shampoo and tablet formulations, and provide pilot data on the in vitro efficacy and in vivo safety of these novel phage formulations for control of canine skin infections.
Key researchers:Ìý¶Ù°ùÌýKate Worthing, ¶Ù°ùÌýCarola Venturini
Escherichia coliÌý²¹²Ô»åÌýStaphylococcus pseudintermedius are the most common bacterial pathogens of dogs, causing both urinary tract and skin and soft tissue infections. In-vivo biofilm production in canine infections has been seldom studied, but the presence of biofilm is presumed to be a complicating factor in refractory UTI and surgical implant infections in dogs, as it is in humans. Two potential novel solutions against biofilm-associated infections are antimicrobial peptides (AMPs) and bacteriophages. The objectives of this study are to optimise in-vitro models of E. coli urinary catheter and S. pseudintermedius implant infections, and to determine the efficacy of bacteriophages and AMPs as anti-biofilm agents.
Defining AMR incidence and developing alternatives to antimicrobials for the treatment and prevention of mastitis, diarrhea, and other bacterial infections.
Key researchers:Ìý¶Ù°ùÌýCarola Venturini,ÌýProfessor Ruth Zadoks,ÌýAssociate Professor Sally Partridge,ÌýDr
The World Health Organization lists Klebsiella pneumoniae among a handful of bacterial species that are major public health threats. K. pneumoniae can not only cause disease in people and animals, but is also a major antimicrobial resistance (AMR) trafficker.
We aim to determine whether humans and animals share their Klebsiella infections, and/or the drug resistance genes of their Klebsiella isolates. This One Health approach will inform best practice for the control of this key pathogen.
Key researchers: Associate Professor Roslyn Bathgate,Ìý¶Ù°ùÌýCarola Venturini
Worldwide, antibiotics are routinely added to boar semen extender to limit microbial growth during storage, as bacteria can impair sperm function and reduce fertility outcomes. This routine practice needs to be re-evaluated in light of antibiotic stewardship guidelines from the FAO, developed as a means to control the rise of antimicrobial resistance. The objectives of this study are to define the bacterial profile of commercially available boar semen in Australia and to establish the viability of antibiotic-free storage on sperm quality.
Key researchers:Ìý¶Ù°ùÌýJosé A Quinteros, ¶Ù°ùÌýKate Worthing, ¶Ù°ùÌýCarola Venturini
Since its first isolation as a pathogen in 2006 from broilers exhibiting severe lameness and locomotor problems,ÌýEnterococcus caecurmÌý(EC) has steadily gained importance in the poultry industry. This project aims to isolate and characterise EC strains circulating in NSW using the Nanopore platform, with the goal of designing better diagnostic tools.
Investigating respiratory disease such as rhodococcal pneumonia in foals.
Key researchers:Ìý¶Ù°ùÌýCarola Venturini, ¶Ù°ùÌýGary Muscatello, Professor Kim Chan,Ìý
The soil saprophyte virulent Rhodococcus equiÌý(RE), when inhaled, causes severe bronchopneumonia in foals (and occasionally in humans), costing the equine industry millions of dollars annually. Bacteriophages offer a promising opportunity for RE control. This project will provide optimised protocols for the preparation of phage sprays and powders effective against RE, as a crucial step in the development of ready-to-use phage-based products for intervention on equine breeding farms for soil decontamination or treatment of foals.
Key researchers:Ìý¶Ù°ùÌýGary Muscatello,Ìý¶Ù°ùÌýMark Westman
There is limited data on antimicrobial resistance in Australian Rhodococcus equi. Given the widespread use of antimicrobials for subclinical respiratory disease in foals, it's crucial to understand if these practices drive resistance. The lack of standard protocols and breakpoints for evaluating R. equi susceptibility is a significant challenge. This project will use modern microdilution antimicrobial sensitivity testing platforms to assess susceptibility patterns, develop breakpoints, and correlate with commonly used methods to advocate for standardised testing regimes.
Characterising emerging opportunistic pathogens associated with increased AMR and climate change.
Key researchers:Ìý¶Ù°ùÌýFrancisca Samsing Pedrals, ¶Ù°ùÌýCarola Venturini,Ìý,ÌýProfessor Joy Becker,ÌýE Turton, R Sullivan, J Sutton
The increasing production demands on aquaculture combined with the effects of climate change on marine ecosystems are primary forces driving the emergence of marine opportunistic pathogens belonging to the Vibrio genus, often carrying multidrug resistance, and source of outbreaks of disease in both seafood and humans. In this study, we explore the use of phages as new ‘ecological’ solutions to pathogen management in aquaculture settings.
Honours
Contributing students and volunteers
For information about opportunities to work or collaborate with OHPAL, please contact ohpal@sydney.edu.au.
