There is a multitude of microbes that the human body can encounter on a daily basis. Normally, the body’s immune system recognizes an infection of foreign microbes and works to remove them so they don’t cause further harm. However, the body can sometimes begin to turn on itself and attack its own tissues instead of the infectious invaders. This results in a disease commonly known as sepsis. 

Sepsis is an extreme bodily response to an infection that can be life-threatening if not properly diagnosed and treated. Later stages of sepsis can result in excessive blood clotting and permanent organ damage. It is estimated that around 30% of patients diagnosed with severe sepsis do not survive and up to 50% suffer from a condition known as post-sepsis syndrome. Recovery is often predicated on the stage at which sepsis is identified and treated by antibiotics, with earlier detection providing more successful recovery outcomes. 

A clinical diagnosis of sepsis currently relies on the presence of specific symptoms, such as decreased oxygen saturation levels and decreased systolic blood pressure. Sepsis can be confirmed by a positive body fluid test, but this typically occurs at a later stage of the disease, if it even occurs at all. Research into early detection and treatment of sepsis is an unmet need that the Mahan Lab at UC Santa Barbara has attempted to address in a research study of over 10 years. The Mahan Lab is headed by professor Michael Mahan and explores various areas of microbial pathogenesis. A team of collaborators spanning multiple universities, including UCSB, UC San Diego and UC Davis, investigated the potential of molecular diagnostic testing in recognizing the early stages of sepsis.

The researchers examined altered blood proteomics in mice after infection from various types of bacteria that are known to cause sepsis. Bacteria from strains of Salmonella enterica, Escherichia coli and Staphylococcus aureus were used, among others. The findings showed a significant change in blood proteins related to septic responses that occurred quickly after a bacterial infection and well before severe symptoms, such as blood clotting and organ failure, were exhibited. Douglas Heithoff, who is one of the lead researchers on the paper and is a part of the Mahan Lab, said the “early detection allowed early antibiotic administration, resulting in markedly increased survival rates.” 

A deep understanding of the altered blood proteomics caused by bacterial infections can help in the development of rapid and easy-to-perform tests to indicate whether a patient is in the early stages of sepsis. Even though the benefits of early administration of antibiotics are well documented, it is ill-advised to administer antibiotics to a patient without a confirmed diagnosis of sepsis. Thus, the findings provide a framework for early-detection molecular sepsis tests to accurately diagnose sepsis in the early stages of the disease. Prospective research will continue to improve the speed at which the disease is recognized and can subsequently be treated by antibiotics. 

In the future, Heithoff said he hopes “to identify a bio-panel of early sepsis blood proteins for incorporation into existing blood tests,” such that patients can be accurately tested for sepsis “in a doctor’s office when they are feeling unwell but are unsure of the cause.”

The goal is that the patient is examined, properly diagnosed and treated with the correct antibiotics well before severe sepsis can occur. Additionally, Heithoff said that “future research will also focus on understanding the mechanism of sepsis caused by different infecting pathogens,” with the hope that significant progress will be made in curtailing the effects of and promoting full recoveries from all potential causes of this serious illness. 

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