Research on and analysis of bacteria is ceaseless, since understanding the pathogens that infect us is the first step to finding effective ways to stop them. An international team of scientists got us one step closer to new preventative approaches and treatment options with a comprehensive, cross-species genomic comparison of leptospira, a complicated bacteria that can cause death and disease in many types of mammals, including humans.

The lengthy analysis revealed leptospira possesses novel adaptations and traits in infectious strains of the bacteria, which can not only help illuminate its evolutionary history, but also aid researchers in coming up with new ways to deal with leptospira. Involving researchers from institutions including Yale, Cornell, UCLA, and various other countries, the study utilized data from for international labs.

“Leptospira is the most complex genus of bacteria that infects humans,” said Dr. Joseph M. Vinetz, a professor of medicine and director of the UC San Diego Center for tropical Medicine and Travelers Health, in a statement. “This work compares the complete genome sequences of all known species of Leptospira to discover which genes make this bacterium a pathogen. It provides a roadmap for future research, including finding new ways to diagnose infection and vaccine development.”

First author Dr. Derrick Fouts, an associate professor at JCVI, initiated the project. He explained that bioinformatics tools have improved to the point where researchers are able to find the “needle in the haystack,” meaning they can find and identify specific genes and pathways that are unique to microbes. This allows scientists to focus research efforts on these key features.

Leptospira is a varied bacteria—some species are non-infectious and derive nourishment from dead matter, others are infectious with dangerous consequences. The bacteria affects different mammals different ways, for example, colonizing the kidneys in rats and mice but not producing disease symptoms, which Leptospira in livestock can cause acute liver, kidney, and lung damage. When humans contract it, a range of effects are possible, from flulike symptoms to jaundice to kidney or liver damage. Leptospirosis, the disease caused by the bacteria, is the most important bacterial disease transmitted from animals to humans, with more than 1 million cases reported and 60,000 deaths every year around the world.

The study uncovered several Leptospira pathogen-specific features, including the discovery of proteins that could accelerate vaccine developments, adaptations of the bacteria to mamals, and the fact that Leptospira evolutionarily gained the ability to synthesize vitamin B12 from a simple amino acid precursor, an ability non-infectious Liptospira lacks.

“One fascinating finding was discovering the CRISPR-Cas genetic machinery only in pathogenic Leptospira, but not in the intermediate or non-infectious groups of the genus,” Vinetz said. “The evolutionary acquisition of novel CRISPR elements, which are only in pathogenic Leptospira, probably hastened adaptation to human infection. The significance of this observation remains to be explored.”

CRISPR-Cas is a sort of molecular immune system, which provides acquired immunity to foreign genetic elements. Vinetz said the next step for researchers will be to exploit the information uncovered for vaccine and diagnostics development, and approaches to understanding pathogenesis how Leptospira exist in the environment.

Source: Fouts D, Haft D, Matthias M, Berg D, Monk J, Palsson B, et al. what makes a bacterial species able to cause a human disease? PLOS Neglected tropical Diseases. 2016.