Written by Mateusz Faltyn, Honours Bachelor of Arts & Science, Mathematics and Statistics Candidate, McArthur Lab
The Whitney Lab is interested in discovering the mode of action of protein toxins delivered between bacterial cells during interbacterial competition. By defining the mechanisms bacteria employ to kill one another, they aim to uncover new targets in the bacterial cell that can be exploited for the development of novel antimicrobials to help combat the ever-increasing problem of antibiotic resistance.
Many scientific investigators affiliated with the Institute for Infectious Disease Research (IIDR) at McMaster University are focused on uncovering the molecular mechanisms that underlie microbial interactions. While this research field is extremely broad and interdisciplinary, it can be organized into two types of interactions: microbe-host interactions and microbe-microbe interactions. Both of these interactions include chemotaxis, signaling, and genetic exchanges. Furthermore, both play a vital role in niche microbial colonization and nutrient acquisition.
Members of the Whitney Lab, led by Dr. John Whitney, Assistant Professor in the Department of Biochemistry and Biomedical Sciences, are primarily interested in better understanding the molecular mechanisms of microbe-microbe interactions. They believe that a greater comprehension of these mechanisms will allow scientists to discover how pathways involved in interbacterial interactions impact human health and the environment. Currently, work conducted in the Whitney lab can be separated into two categories: (1) interbacterial competition by the type VI Secretion System of Gram-negative bacteria, and (2) interbacterial competition by the type VII secretion system of Gram-positive bacteria. This newsletter will explore the history of the type VII secretion system, as well as relevant work done in the Whitney lab by Ph.D candidate Tim Klein.
Most bacteria are classified as either Gram-negative or Gram-positive. Bacteria within these two groups have many similarities; for example, they each have a bacterial cell wall that is made out of peptidoglycan and they both produce exotoxins. However, they differ in the thickness of their cell wall and by the number of cellular membranes they possess. This difference influences how they appear when subjected to a Gram staining procedure. Gram-positive bacteria have thick layers of peptidoglycan and stain purple; Gram-negative bacteria have a thin layer of peptidoglycan with an outer membrane and stain pink.
One of the interesting differences between Gram-negative and Gram-positive bacteria is the challenge of exporting proteins from the cell. This process is more complicated in Gram-negatives because of the outer membrane and thus requires the use of specialized secretion machines that exist in the cell envelope. A significant amount of research has been carried out on the specific secretion systems (numbered I through VI) employed by Gram-negative bacteria to secrete proteins across their inner and outer membranes. In contrast, it was long thought that because Gram-positive bacteria only possess a single membrane, they could rely on the ubiquitous general protein secretory pathway found in all domains of life. This paradigm continued to dominate the literature until 1996 when it was found that a new specialized secretion system, ESX-1, existed in the bacterium Mycobacterium tuberculosis. Further studies revealed that the ESX-1 system plays a critical role in M. tuberculosis virulence, as a number of ESX-1 exported proteins interfere with host immune responses and functions. In order to align this newly discovered secretion system with the nomenclature used to describe Gram-negative secretion systems, the ESX-1 system was renamed to the type VII secretion system. It is now known that the type VII secretion system exists more broadly throughout Gram-positive bacteria including in clinically relevant pathogens such as Staphylococcus aureus.
Recent work in the Whitney lab has found that in addition to its role in virulence, the type VII secretion system exports antibacterial proteins that mediate interbacterial competition. Furthermore, they found that bacteria produce immunity proteins that protect themselves and their sister cells from the activities of their own toxins. Their 2018 publication titled Molecular Basis for Immunity Protein Recognition of a Type VII Secretion System Exported Antibacterial Toxin explores the interaction between one of these toxins and its cognate immunity protein. In addition to understanding the mechanisms of microbe-microbe interactions, the Whitney Lab hopes that defining the mode of action of antibacterial toxins will lead to the identification of new vulnerabilities in Gram-positive cells that can be exploited for the development of new antibiotics. For more information on the current research conducted in the Whitney Lab, please visit their website.
About the Author
Mateusz Faltyn, Honours Bachelor of Arts & Science, Mathematics and Statistics Candidate
Mateusz is entering his third year in the Honours Bachelor of Arts and Science Undergraduate program at McMaster University. Currently, he is a member of Dr. Andrew McArthur’s lab. Mateusz enjoys reading and coding, as well as watching Game of Thrones.