Each year, Americans develop over 1.5 million cases of sepsis as a result of bacterial infections. More than a quarter of a million of these cases prove fatal. Now, a powerful new diagnostic system could radically improve these statistics, with a first-of-its-kind test that can simultaneously screen for all known human pathogenic bacteria while identifying the genes that give rise to antibiotic resistance. The platform, called BacCapSeq, was designed by researchers at Columbia University, who say it has the potential to significantly accelerate the diagnosis of lethal bacterial infections, ultimately helping to save thousands of lives annually. “Once approved for clinical use, BacCapSeq will give physicians a powerful tool to quickly and precisely screen for all known pathogenic bacteria, including those that cause sepsis, the third leading cause of death in the United States,” says geneticist Orchid M. Allicock from the university’s Centre for Infection and Immunity (CII). “This platform is 1,000 times more sensitive than traditional unbiased testing, at a level comparable to tests that screen one bacterium at a time.” At present, the most common form of sepsis diagnosis involves cultivating bacteria in culture, which can commonly take between two to several days to perform, if not longer for difficult-to-cultivate species. Right now, BacCapSeq delivers results in 70 hours a time-frame that won’t always be faster but the researchers say the lag will reduce with expected advances in computing power. Before that happens, though, the system has other advantages to consider. BacCapSeq follows the lead of a similar tool for all known viral infections, called VirCapSeq-VERT, developed by some of same researchers in 2015. While VirCapSeq-VERT can identify the 207 viral taxa known to infect vertebrates, BacCapSeq goes further, and is capable of detecting the signature DNA of the 307 different kinds of known pathogenic bacteria, while also simultaneously assessing their virulence and antimicrobial resistance. Considering the next most-advanced pathogen identification tool multiplexed polymerase chain reaction (PCR) systems can only screen for up to 19 pathogenic bacteria, it’s a huge leap forward, and a paradigm shift for those in health. “Microbiological intelligence must be an integral component of precision medicine,” says CII director and senior researcher W. Ian Lipkin. “Accurate, early differential diagnosis of infectious diseases and knowledge of drug sensitivity profiles will reduce mortality, morbidity, and health care costs.” BacCapSeq works by using 4.2 million molecules called oligonucleotides that work as genetic probes by binding to sequences of DNA in bacteria lurking in blood samples. The same trick doesn’t just detect bacteria, but also any markers of known antimicrobial genes. To test the diagnostic tool, the team ran it on blood samples ‘spiked’ with nasties like several bacterial payloads including Escherichia coli, Neisseria meningitidis, Salmonella enterica and more, and in each case the platform’s sensitivity saw it outperform conventional pathogen tests such as ultra-high-throughput screening. The researchers acknowledge some limitations to the new system. Because the test is qualitative, not quantitative, in terms of bacterial identification, it can’t replace PCR assays in scenarios where knowing the amount of bacteria is important. Furthermore, it’s only as good as our genetic knowledge of existing pathogens a novel bacterium that differs from known pathogens by more than 40 percent of its coding sequence would go undetected. So, there’s room still for improvement, not that the team being BacCapSeq are exactly taking it easy. Having already transformed the future landscape of bacterial and viral diagnosis, the researchers are now working on a third system one that can do the same thing for fungal infections. Fungus, it’s been real. The findings are reported in mBio.
Science Alert, 28 October 2018 ; http://www.sciencealert.com.au