Hospital Acquired Bacterial Pathogens

Hospital Epidemiology

Immuno-compromised Hosts

Project leader: Prof Anton Peleg

Phone: +61 3 9076 8491

Email: anton.peleg@monash.edu

Overview

Our research program focuses on the mechanisms of pathogenesis of important hospital-acquired pathogens. More specifically, Acinetobacter baumannii, an emerging gram-negative bacterium, Staphylococcus aureus, a gram-positive bacterium, and Candida albicans, the most common human fungal pathogen. We combine bacterial and fungal genetic techniques with exciting in vivo infection model systems (mammalian and non-mammalian [Caenorhabditis elegans and Zebrafish]) to characterise the role of novel genes in virulence and antimicrobial resistance. Our over-arching goal is to identify new targets that may be amenable for future drug development, with a focus on microbial virulence, persistence, and adaptation.

Research

Our research focuses on hospital-acquired infections and their causative organisms. It is estimated that ~ 5% – 10% of all hospital admissions are complicated by a hospital-acquired infection. These types of infections also pose a significant risk to immunocompromised individuals. Unfortunately, these infections are often caused by organisms that are resistant to many antibiotics. The antibiotic development pipeline is very limited and now, more than ever, we need to identify new strategies and targets to prevent or treat hospital-acquired pathogens. Our research involves clinical, translational and basic science aspects of hospital-acquired infections.

Clinical and Translational

These research projects focus on the treatment and epidemiology of antibiotic-resistant organisms and specific patient groups at the Alfred hospital or its affiliated centers:

  1. Infections in patients with cystic fibrosis – we have a prospective clinical trial assessing the efficacy of continuous infusion ?-lactams compared to the current standard practice of intermittent bolus infusion. This study involves the collection of clinical data, as well as microbiological data.

  2. Infections in the Intensive Care Unit – this work focuses on the epidemiology of antibiotic resistance in this setting and transmission dynamics.

  3. Antibiotic use and resistance in long-term care facilities affiliated with the Alfred hospital

  4. Infections in patients with burns, stem cell transplantation, and lung transplantation


Laboratory Research

Our laboratory research is focused on three main hospital-acquired pathogens:

1) Acinetobacter

This is a gram-negative bacterium that has caused problems in hospitals throughout the world. It particularly causes pneumonia in patients on mechanical ventilation and bloodstream infection. Strains resistant to all currently available antibiotics have now been reported. We study the mechanisms Acinetobacter uses to make humans sick, and hope that by identifying these, we can target them to treat or prevent infection. We combine bacterial genetic techniques with dynamic infection models to characterise the role of specific genes.

2) Staphylococcus spp.

Methicillin-resistant S. aureus (MRSA) remains a major problem in the hospital setting and is emerging as a threat in the community setting as well. Our work focuses on mechanisms of antibiotic resistance in staphylococci and how this resistance impacts host-pathogen interactions. Resistance evolution is assessed using whole-genome sequencing and individual genes are then characterised using targeted mutagenesis and complementation. A range of virulence characteristics are assessed including virulence within a mouse bacteremia model.

3) Candida albicans

The most common human fungal pathogen and particularly infects the most vulnerable patients including those who are immunosuppressed and in intensive care unit environments. Mucosal disease is common but invasive disease such as bloodstream infection is the most lethal. A critical virulence determinant of Candida is its ability to transition from a round cell known as yeast to a long filament like cell known as hyphae. We use the non-mammalian model system, Caenorhabditis elegans to study the mechanisms of this important virulence attribute. We also study how Candida forms biofilms on medical devices and develop strategies for its treatment or prevention.

For information regarding research opportunities, please contact Professor Peleg

Contact person: Prof Anton Peleg

Phone: +61 3 9076 6076

Email: anton.peleg@monash.edu

All other student inquiries:
Please contact Brian Price (Business & Community Services Manager)

Email: brian.price@monash.edu

Other links:

Article: Infectious diseases researcher wins prestigious award