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Peleg Lab research

CollaborationsStudent research projects | Publications

About Professor Anton Peleg

Anton Peleg is Professor of Infectious Diseases and Microbiology and Director of the Department of Infectious Diseases at the Alfred Hospital and Monash University. He is also the Infection and Inflammation theme leader for Monash Partners, and a research group leader in the Department of Microbiology, Monash University. His research spans clinical to basic research, with a focus on hospital-acquired infections, antimicrobial resistance, infections in immunocompromised hosts and understanding mechanisms of disease caused by hospital pathogens. He has a particular clinical interest in complex infections in highly vulnerable patient groups, including patients with cystic fibrosis, lung and stem cell transplant recipients, and infections in patients with burns or in intensive care.

MBBS (Hons), 1998 Monash University
PhD (Deans Award), Microbiology and Infectious Diseases, 2010, External PhD at Harvard University through University of Queensland
MPH, 2009, Harvard School of Public Health, Boston, MA USA
FRACP, 2005, Royal Australian College of Physicians


Our research

Current projects

1. Impact of antimicrobial resistance on immune recognition of Staphylococcus aureus
2. Impact of antimicrobial resistance upon virulence and persistence in Staphylococcus aureus
3. Understanding the biology of Acinetobacter baumannii including;

- characterisation of small rnas and novel virulence factors

- defining the drivers of innate immune responses

4. Deciphering the contribution of different metabolic pathways to bacterial survival
5. Understanding the genetic and phenotypic drivers of lateral gene transfer in clinical isolates

Visit Professor Peleg's Monash research profile to see a full listing of current projects.

Research activities

Our research focuses on antimicrobial-resistant (AMR) and hospital-acquired infections and their causative organisms. The antibiotic development pipeline is very limited and now, more than ever, we need to identify new strategies and targets to prevent or treat AMR and hospital-acquired pathogens. Our research involves clinical, translational and basic science aspects of hospital-acquired infections.

Our laboratory research is focused on three main hospital-acquired pathogens, and we also focus on microbial biofilms and medical device infections.

1. Acinetobacter baumannii

A. baumannii is an opportunistic human pathogen causing both hospital and community acquired infections, responsible for a range of disease types including wound infections, pneumonia and bacteraemia. Ranked by the World Health Organisation as the most critical pathogenic threat to the future of human health, due to rampant levels of antibiotic resistance in many hospital-acquired A. baumannii strains, and their propensity to develop resistance to current therapeutics. There is currently only a limited understanding of the virulence factors responsible for the success of A. baumannii as a pathogen. The Peleg laboratory focus on not only elucidating the molecular mechanisms responsible for A. baumannii pathogenesis, but also understanding the host factors that contribute to its success. By enhancing our understanding of these unique host-pathogen interactions we aim to lead the development of novel therapies and assist in the prevention of these infections.

Our current research couples genetics, bioinformatics and phenotypic assays (including in vivo models) to elucidate the differences observed between clinical isolates responsible for hospital and community acquired infections, characterise putative virulence factors, understand the contribution of environmental factors, and the molecular mechanisms regulating gene expression both in vitro and in vivo, and examining how the host immune responses can modulate bacterial gene expression.

This figure shows histopathological section taken at 2 h through a localized somatic muscle infection with A. baumannii–GFP. Neutrophils are red fluorescent with DAP counterstain (white arrow indicates phagocytosed bacteria).

2. Staphylococcus aureus

S. aureus is one of the most common human bacterial pathogens, and is able to cause a wide range of life-threatening infections in the community and hospital setting. As a consequence of the rising rates of methicillin- resistant S. aureus (MRSA), agents such as vancomycin and daptomycin have been increasingly relied upon. Unfortunately, reduced susceptibility to these agents has now emerged. By using large-scale, whole-genome sequencing of clinical S. aureus isolates, whereby the first isolate is susceptible and the paired isolate is non-susceptible, we focus on describing the genetic evolution of antibiotic resistance in patients. Interestingly, we have also identified, using both mammalian and non-mammalian infection model systems, that these resistant strains are attenuated in virulence when compared to their susceptible progenitors but appear more persistent in vivo, mimicking what is observed clinically. We have identified a novel metabolic adaptation strategy used by S. aureus to simultaneously circumvent killing by daptomycin and attacks from host innate immune cells, which enhance bacterial survival during infection. Understanding the relationship between antibiotic resistance and host-pathogen interaction gives us insight into new strategies to prevent and treat infections caused by this organism.

This figure shows antibiotic resistant S. aureus cells (A23V, T33N, L52F) compromised recruitments of fluorescent innate immune cells to the infection sites (rectangule).

3. Emerging antibiotic resistance and lateral gene transfer

The rapid dissemination of antibiotic resistance determinants across bacterial and fungal species threatens to return modern medicine to a pre-antibiotic era. As the levels of multi and pan drug resistance has continued to grow over recent years, so has our surveillance of hospital environments and specifically the appearance and transmission of bacterial strains harbouring genes responsible for antibiotic resistance. Worryingly, during the last decade we have increasingly observed the lateral transfer of genes promoting antibiotic resistance across not only different species but also different genera of Gram negative bacteria.

Using a combination of next generation sequencing paired with in vitro assessment of contemporary and historical clinical isolates, the Peleg lab aims to uncover the mechanisms responsible for this lateral transfer of antibiotic resistance genes, to understand not only the genetic context in which they are encoded, but also the ‘signals and triggers’ that promote their dissemination and the mechanisms by which they are mobilised from one genera to another.

By elucidating the drivers of these processes we can advise and direct clinicians and hospital practises, respectively, to minimise the potential for these ‘gene outbreaks’ and  the dissemination of these dangerous genetic determinants.

The figure denotes the genetic conservation between plasmids isolated from different Serratia marcescens isolates taken from patients and the hospital environment. The regions highlighted in grey indicate greater than 90% sequence homology between the samples. The bioinformatics assessment confirms these plasmids encoded conserved loci responsible for their mobilisation (conjugation loci) and antibiotic resistance capacity (class I intergron and β–lactamase genes).

4. Microbial biofilms and medical device infections

Another research interest of our group is to understand the role of biofilms in the pathogenesis of many hospital acquired infections: how bacteria and fungi adhere to medical devices and form biofilms, how this planktonic-biofilm phenotypic change leads to high resistance to antimicrobials and human defences, and what external factors (environmental aspect) and internal factors (cellular aspect) regulate biofilm formation of the microorganisms. Our current biofilm research has a very broad pathogen coverage, including the fungal pathogen C. albicans, gram-negative bacteria Klebsiella pneumoniae, A. baumannii and P. aeruginosa and gram-positive bacteria Staphylococcus epidermidis and S. aureus. We are currently studying biofilm formation and migration on ventricular assist device (VAD) drivelines, from both in vitro and in vivo aspects. Ventricular assist devices have been successfully used to manage acute and chronic end stage cardiac disease. Long-term VAD success is limited predominantly by the occurrence of exit-site infections and pocket infections, due to microbial biofilms formed on implanted drivelines. The specific biofilm growth mode equips the pathogens extreme resistance to conventional antimicrobial treatments and the human immune system, and is believed to be the cause of persistent infections. We work closely with engineers from Commonwealth Scientific and Industrial Research Organisation (CSIRO), and cardiac surgeons from the Alfred hospital, aiming to develop new antimicrobial strategies to prevent biofilm-related infections.

This scanning electron microscopy image shows microbial biofilm formation on the ventricular assist device driveline smooth (left panels) and velour sections (right panels) using a drip-flow biofilm reactor.

Techniques/expertise

Antimicrobial resistance
Hospital acquired infections
Molecular genetics of bacterial and fungal pathogens
Host-pathogen interactions
Genomic, transcriptomic and metabolomic analyses of AMR bacteria

Disease models

Zebrafish and murine models for the study of host-pathogen interactions, for S. aureus and A. baumannii, with models mimicking pneumonia and bacteraemia.

The roundworm (C. elegans) to assess virulence and to identify novel factors.


Collaborations

We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

Prof Graham Lieschke (Australian Regenerative Medicine Institute, Monash University)
- Study of host-pathogen interactions using Zebrafish

Prof Ben Howden (Microbiological Diagnostic Unit, the University of Melbourne)
- Pathogenic and resistance mechanisms of Staphylococcus aureus

A/Prof Meredith O’Keeffe (Biochemistry & Molecular Biology)
-Dendritic cell response toward antibiotic resistant S. aureus

A/Prof Max Cryle (Biochemistry & Molecular Biology)
-Novel glycopeptides antibiotic development

Dr. Hsin-Hui Shen (Faculty of Engineering and  Dept of Molecular Biology and Biochemistry)
-Novel antimicrobial nanoparticles formulation

Dr. Jeremy Barr (School of Biological Sciences)
-Bacteriophage therapy

Prof Malcolm McConville (Bio21 Molecular Science & Biotechnology Institute)
-Metabolomic analysis of antibiotic resistant bacteria

A/Prof. Ana Traven (Dept of Molecular Biology and Biochemistry)
- Candida albicans virulence

A/Prof. John Boyce (Dep. Microbiology)
-Genetic regulation of A. baumannii pathogenesis

Prof. Dena Lyras (Dept. Microbiology)
- Gene transfer of antibiotic resistance determinants in clinical isolates

Prof. Ian Paulsen (Macquarie University)
-Genomics and application of next gen sequencing

Prof. Bayden Wood and Philip Heraud (Centre for Biospectroscopy)
-New, rapid sepsis diagnostics


Student research projects

The Peleg Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Supervisor Connect to explore the projects currently available in our Lab.