A race against time: flesh-eating bacteria
The broad spectrum of causative bacteria complicates accurate diagnosis and appropriate treatment of necrotizing soft tissue infections (NSTIs). Our work aims to reduce time from hospital admission to microbial diagnosis by generating new insights into the molecular pathophysiology of NSTIs.
‘Leg amputated after contracting flesh-eating bacteria’
‘Patient dies after battling infection with flesh-eating bacteria’
Headlines like these have become increasingly common in recent years. Clinicians attribute the increase of such news stories to the effects of global warming, as one of the bacterial species causing these infections (Vibrio vulnificus) is commonly contracted during bathing in tempered waters. With increasing water temperatures, ‘flesh-eating’ bacteria are spreading to new areas.
The pathology behind the headlines is called necrotizing soft tissue infections (NSTIs). These rare, but devastating infections are most notable for their rapid progression, high mortality and widespread tissue destruction, often necessitating rapid surgical intervention and amputation. While NSTIs can occur in healthy individuals of all age groups, they are most common in patients with recent surgical interventions, immunodeficiencies or other medical conditions. Frequent causes for NSTIs are therefore not water-borne Vibrio, but clinically well-known pathogens like Streptococcus pyogenes. Importantly, NSTIs are associated with a spectrum of different bacteria, including complex polymicrobial communities, which complicates microbial diagnosis. Rapid diagnosis, however, is critical for the implementation of appropriate treatment that can minimize patient mortality, particularly in an age where bacteria are becoming increasingly resistant to antibiotics. Moreover, the lack of knowledge about how NSTIs caused by different bacteria differ poses a major obstacle for the development of novel strategies to bear down on these vicious infections.
Recognizing these deficiencies, the EU funded the ‘INFECT’ project under the FP7-Health program to improve knowledge of pathophysiology, prognosis and diagnosis of NSTIs. In this project, a multi-disciplinary team of researchers, clinicians, biotech companies, and patient organizations from across Europe, Israel and the US came together to improve diagnosis and therapeutic strategies to achieve better patient outcomes. In this unique collaborative effort, clinicians and researchers were able to not only generate novel insights into the disease, but also established the world’s largest NSTI patient cohort and sample collection.
Leveraging this unique resource, our work focused on generating a knowledge base on bacteria involved in NSTIs and a better understanding of the subtle differences of NSTIs caused by different bacteria to enable clinicians to promptly and correctly diagnose and treat these infections. We were able to show that cooperating communities of bacteria that are common inhabitants of the healthy human intestine, skin and oral microbiota (called ‘pathobionts’) can cause infections that are of similar mortality and destructive potential as those caused by ‘professional pathogens’ like Streptococcus pyogenes. The molecular mechanisms that cause the widespread tissue destruction, however, varied substantially between polymicrobial infections associated with pathobionts and those caused by pathogenic Streptococci. While Streptococciproduced high levels of cytotoxic factors, division of labor between pathobionts in polymicrobial infections enabled these communities to colonize and trigger a destructive inflammatory immune response within the infected tissue. These observations create a new understanding of the complex inter-bacterial interactions that enable communities of benign bacteria to cause devastating necrotic infections.
Importantly, we show that these unique properties of streptococcal and polymicrobial infections could be exploited to derive rapid, accurate bacterial diagnosis. The unique characteristics of the colonizing bacterial communities elicit different responses within the infected tissue that are also detectable in blood serum. These signatures could be used to, within hours, inform clinicians about the identity of the the infecting bacteria, a process that could otherwise take days as microbial diagnosis is still reliant on the results of slow growing bacterial cultures. In the age of antibiotic resistance, expediated diagnosis is more important than ever. We hope that our work can inform the search for a set of clinically reliant biomarkers that will help to improve rapid microbial diagnosis of NSTIs and ultimately reduce the mortality of these traumatic infections.
Link to paper: https://rdcu.be/bPyHp