New publication :
Bacterial cell wall peptidoglycan is essential, maintaining both cellular integrity and morphology, in the face of internal turgor pressure. Peptidoglycan synthesis is important, as it is targeted by cell wall antibiotics, including methicillin and vancomycin. Here, we have used the major human pathogen Staphylococcus aureus to elucidate both the cell wall dynamic processes essential for growth (life) and the bactericidal effects of cell wall antibiotics (death) based on the principle of coordinated peptidoglycan synthesis and hydrolysis. The death of S. aureus due to depletion of the essential, two-component and positive regulatory system for peptidoglycan hydrolase activity (WalKR) is prevented by addition of otherwise bactericidal cell wall antibiotics, resulting in stasis. In contrast, cell wall antibiotics kill via the activity of peptidoglycan hydrolases in the absence of concomitant synthesis. Both methicillin and vancomycin treatment lead to the appearance of perforating holes throughout the cell wall due to peptidoglycan hydrolases. Methicillin alone also results in plasmolysis and misshapen septa with the involvement of the major peptidoglycan hydrolase Atl, a process that is inhibited by vancomycin. The bactericidal effect of vancomycin involves the peptidoglycan hydrolase SagB. In the presence of cell wall antibiotics, the inhibition of peptidoglycan hydrolase activity using the inhibitor complestatin results in reduced killing, while, conversely, the deregulation of hydrolase activity via loss of wall teichoic acids increases the death rate. For S. aureus, the independent regulation of cell wall synthesis and hydrolysis can lead to cell growth, death, or stasis, with implications for the development of new control regimes for this important pathogen.
You can read our new publication Demonstration of the role of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics in PNAS.
The effect of cell wall antibiotics on PG architecture.
New publication :
S. aureus is a commensal inhabitant of the human skin and nares. However, it can cause serious diseases if it is able to breach our protective barriers such as the skin, often via wounds or surgery. If infection occurs via a wound, this initial inoculum contains both the pathogen, other members of the microflora and also wider environmental microbes. We have previously described “augmentation”, whereby this other non-pathogenic material can enhance the ability of S. aureus to lead to a serious disease outcome. Here we have determined the breadth of augmenting material and elucidated the cellular and molecular basis for its activity. Augmentation occurs via shielding of S. aureus from the direct bactericidal effects of reactive oxygen species produced by macrophages. This initial protection enables the effective establishment of S. aureus infection. Understanding augmentation not only explains an important facet of the interaction of S. aureus with our innate immune system, but also provides a platform for the development of novel prophylaxis approaches.
You can read our new publication Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species in PLOS Pathogens.
21st May 2021
Lab social... finally!
After a long wait we finally got to have a covid-safe lab trip to the University Arms - great fun, even if it was a bit rainy!
Sutton JAF, Carnell OT, Lafage L, Gray J, Biboy J, Gibson JF, et al. (2021) Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction. PLoS Pathog 17(3): e1009468.
31st March 2021
New publication :
Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction
Methicillin resistant Staphylococcus aureus (MRSA) is a great threat to human healthcare. To discover new control regimes, it is important to understand how the pathogen behaves within the host environment. Here, we initially developed methods to isolate S. aureus from an infected host for biochemical and morphological analyses. This revealed host associated adaptations which in turn suggested the role of specific cell wall homeostatic mechanisms during infection. We tested the role of several components in disease, demonstrating a crucial function for cell wall dynamics during the complex interaction with the host, giving novel avenues to explore for future prophylaxis and therapy.
You can read our new publication Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction in PLOS Pathogens.
19th January 2021
New publication :
The Role of Macrophages in Staphylococcus aureus Infection
In this review we examine macrophage-S. aureus interactions through early and late stages of infection. The important role of macrophages in controlling S. aureus infection is highlighted, including the mechanisms used to kill invading bacteria. We also discuss strategies used by S. aureus to evade or subvert macrophage functions to promote infections.
You can read our new publication The Role of Macrophages in Staphylococcus aureus Infection in Frontiers in Immunology.
11th December 2020
F18's Virtual Xmas party
Had a great Christmas party with an awesome festive quiz from Bartek and Josh!
26th November 2020
New PhD Opportunity :
To kill and cure: Understanding antibiotic action to enhance activity
Antibiotics are at the core of modern medicine, but they are under threat due to the spread of resistance. Antibiotics either kill (bactericidal) or stop bacteria growing (bacteriostatic). Extraordinarily we still do not know why only some antibiotics kill or what mechanism(s) lead to death.
4th November 2020
Viva congratulations to Laia!
Massive congrats to Dr. Laia Pasquina-Lemonch on passing her viva!
The Foster lab are looking forward to continuing work together in the future
Evolution of Beta-Lactam resistance in MRSA
The model system constructed in this work mimics the naturally occurring MRSA, to understand the underpinning mechanisms of S. aureus which develop high-level resistance. Our study reveals a novel effect of mecA acquisition and compensatory mutations on central metabolism and sheds light on potential pathways essential for high-level resistance.
You can read our new Publication Evolution of Beta-lactam resistance in MRSA in PLOS Pathogens.
26th June 2020
Congratulations Dr. Sutton
A huge congratulations to Josh for passing his viva! Well deserved Prosecco in the park.
All of the Foster lab wish you the best of luck in the future!
The architecture of the Gram-positive bacterial cell wall
New research, published in Nature, revealed a new and unexpected structure of the outer bacterial layers of the bacterium Staphylococcus aureus. Click here to read
Scientists from the Hobbs and Foster Labs at the University of Sheffield have produced the first high-resolution images of the structure of the cell wall of bacteria using Atomic Force Microscopy (AFM), in a study that could further understanding of antimicrobial resistance.
The findings set a new framework for understanding how bacteria grow and how antibiotics work, overturning previous theories about the structure of the outer bacterial layers.
Simon's Virtual seminar
Simon delivered a talk titled Bacterial Cell Wall Architecture and Dynamics: A Matter of Life and Death as part of the virtual S.aureus seminar series.
F18 Christmas 2019
Awesome F18 Christmas social featuring
mince pies, a winter walk, dinner,
drinks and the Turkey hat!