BiothreatsDistinguishing virulent from harmless bacteria to help biological surveillance

Published 25 August 2017

Biological “detectives” are tracking down biothreats such as the bacteria that causes tularemia (“rabbit fever”), but they constantly face the challenge of avoiding false positives. Sounding the alarm over a bioattack, only to find it’s a harmless relative in the same genus, reduces credibility and public trust. Researchers are narrowing down the confusion over Francisella bacteria, a few species of which include highly virulent human and animal pathogens, fish pathogens, opportunistic human pathogens, tick endosymbionts, and free-living isolates inhabiting brackish water.

Biological “detectives” are tracking down biothreats such as the bacteria that causes tularemia (“rabbit fever”), but they constantly face the challenge of avoiding false positives. Sounding the alarm over a bioattack, only to find it’s a harmless relative in the same genus, reduces credibility and public trust. New work at Los Alamos National Laboratory is narrowing down the confusion over Francisella bacteria, a few species of which include highly virulent human and animal pathogens, fish pathogens, opportunistic human pathogens, tick endosymbionts, and free-living isolates inhabiting brackish water. 

“Accurate discrimination among the virulent subspecies of F. tularensis and the environmentally abundant F. novicida and its relatives is absolutely critical for the future success of biological surveillance and attribution activities,” said Los Alamos biologist Jean Challacombe, lead author on a paper published in PLOS ONE. LANL notes that biological surveillance, such as that conducted by the U.S. Department of Homeland Security and the Department of Defense, provides early warning of infectious disease outbreaks, hazardous environmental exposures, or possible bioterrorist attacks by spotting trends of public health importance.

The Francisella genus includes several recognized species, additional potential species, and other representatives that inhabit a range of incredibly diverse ecological niches but are not closely related to the named species. Many of them cause no problems for humans or livestock. F. tularensis, however, is a highly virulent zoonotic pathogen (spreads from animals to humans) that causes tularemia. Because of weaponization efforts in past world wars, it is considered a first tier (most serious) biothreat agent.

The bad one, F. tularensis subspeciestularensis (Type A), is found exclusively in North America and is the most virulent, causing the disease tularemia. It can produce skin ulcers, chest pain and difficulty breathing.

The team has identified several apparently cryptic plasmids—which are linear or circular structures of double-stranded DNA capable of existing outside the chromosome—in the sequenced genomes of three commonly found environmental Francisella species. These plasmids provide additional phylogenetic and genomic features that differentiate pathogenic F. tularensis strains from clinical and environmental near-neighbor species that are not biothreat agents.