"We expected to find resistance genes," said lead author, Pierre-Edouard Fournier, researcher at the Structural and Genomic Information Laboratory at France's National Center for Scientific Research (CNRS). "But the grouping of most of these genes within a single genomic island was totally unexpected." The resistance island--a group of resistance genes clustered close together on a chromosome--is the largest discovered to date.
The research team also discovered new resistance genes. "We were surprised to discover 19 new resistance genes that escaped the scrutiny of the large number of laboratories already working on multi-drug resistant A. baumannii throughout the world. This is a demonstration of the efficiency of the whole genome approach in characterizing new pathogens," said Jean-Michel Claverie, senior author of the report and Director of the Structural and Genomic Information Laboratory at CNRS.
This bacterium acquires resistance genes quickly--just thirty years ago it was completely susceptible to antibiotics and now it is resistant to a wide-range of antibiotics.
"A. baumannii is exceptionally prone to pick up foreign DNA from other bacteria," Claverie said. The study traced the origin of many resistance genes to other bacteria, including Salmonella, indicating frequent genetic swapping between bacteria.
Resistance genes are usually located on small auxiliary circles of DNA called plasmids that can be exchanged with other individuals. But in A. baumannii, resistance genes were incorporated into the main chromosome, not the plasmids, according to the study.
"It is like the A. baumannii genome is 'anticipating' any antibacterial challenge by setting up some kind of easily accessible 'shelves' to store the antibacterial resistances genes as they become needed and are available in the environment," Claverie said.
The research team compared the entire genomes of two A. baumannii strains, one completely susceptible to antibiotics and one highly resistant.
"This is the first study of its kind to study the resistance mechanisms of a bacterial strain by whole genome sequencing," said Fournier. "Our strategy of sequencing the whole genome of a bacterial strain with specific features is valuable and fast."
Resistant A. baumannii has become a major public health concern worldwide. Recently, a high incidence of resistant A. baumannii was reported in US Army service members injured in Afghanistan and Iraq. In France, the resistant strain is widespread in 54 healthcare facilities, where 26% of infected patients die.
"Less than 2 years after the start of the French epidemic episode, we found the complete genome ID of the microbe involved and developed a better understanding of what to expect for the future, in terms of new antibiotic resistance," Claverie said. "This work will guide a future international effort on identifying all major A. baumannii resistant strains throughout the world, and help follow the emergence of new strains and understand their mode of evolution."