Tuesday, December 10, 2013

How Staphylococcus Aureus Evades and Undermines the Immune Response

Staphylococcus aureus is a bacterial pathogen that is largely responsible for human infections that impact the skin and soft tissue.   These kinds of infections can be serious enough to lead to life threatening conditions such as sepsis (blood poisoning as a result of microorganisms or the toxins they produce), endocarditis (inflammation of the interior lining of the chambers of the heart) and bacteremia (bacteria in the blood).  A distinctive characteristic of a staphylococcal infection is the formation of abscesses that are comprised of bacterial colonies surrounded by fibrin – a structural protein.  The severity of infections with this organism has been attributed to its ability to evade and undermine the immune response.   It is, therefore, essential to understand the nature of its mechanism of action in regard to defending itself from the immune system.

Human immunity can be delineated into two distinct responses.  The first if referred to as the “innate” response and the second as the “adaptive” response.  The former is designed to respond immediately to an invasion by deleterious organisms such as bacteria.   The adaptive response is typically secondary and engages the T and B lymphocyte populations that are in constant circulation within the blood and lymph systems.  This response affords more enduring and long term immunity to the insulting microorganism(s).
As part of the innate response to Staphylococcus aureus infection, neutrophils – white blood cells that move to the site of infection – release their DNA in the a form that is referred to as neutrophil extracellular traps (NETs).   The intrinsic purpose of these NETs is to immobilize the pathogen and enhance the activity of peptides – small proteins – that possess anti-bacterial activity.  However, Staphylococcus aureus effectively undermines this immune response.

The mechanism of action that the pathogen employs to counteract the role of neutrophils has been characterized through the efforts of Dr. Vilasack Thammavongsa and his colleagues at the Department of Microbiology of the University of Chicago.   As a result of their research efforts, they discovered that staphylococcus aureus sidesteps the innate immune response by effectively converting NETs to deoxyadenosine.   This modification is a product of two enzymes – nuclease and adenosine synthase – secreted by the pathogen.  This action triggers the destruction of immune cells and also prevents macrophages – white cells whose role is to ingest invading organisms - from entering the staphylococcal abscesses.

This finding is of great value; for, it helps elucidates the mechanism through which staphylococcus successfully evades the human immune system.