Using DNA sequencing, the researchers found that insertion mutations in 116 genes were particularly abundant after at least 24 hours of growth in the murine models. One of the mutations isolated affected the oprD gene, which were previously linked to antibiotic resistance in P. aeruginosa-infected patients. Another, in the glpT gene is known to confer resistance to antibiotics in Escherichia coli. Both genes serve similar functions: oprD encodes a channel that allows carbapenem antibiotics to enter bacterial cells, while glpT permits a different antibiotic, fosfomycin, to get into cells.
These transposon mutants—as well as two strains isolated from patients with P. aeruginosa—were more virulent compared to antibiotic-sensitive strains in the mouse lung infection models. The glpT mutant could even kill macrophages in vitro, the researchers found, suggesting that the antibiotic resistance may be linked to the ability of P. aeruginosa to evade attack by the host immune system. Moreover, transposon mutants in genes that normally provide intrinsic drug resistance had a growth disadvantage in the mouse models of lung infection.
The researchers demonstrated similar results in both Acinetobacter baumannii and Vibrio cholera. “The new picture emerging from this work is that antibiotic resistance is not [necessarily] associated with a fitness cost, and is even associated with an increased fitness and an increased virulence,” Skurnik told The Scientist.
The team’s results do not suggest that antibiotic resistance is always linked with increased virulence or fitness in these three, or other species of pathogenic bacteria. And they only pertain to the loss-of-function mutations examined. Whether gain-of-function mutations or plasmid-borne antibiotic-resistance genes have similar effects on bacterial fitness and virulence has yet to be seen.
“The results are interesting, but I don’t think the findings challenge the idea that most [antibiotic-resistance mutations] confer reductions in fitness when measured in vitro or in vivo,” Dan Andersson, who studies bacterial evolution at Uppsala University in Sweden and was not involved in the study, wrote in an e-mail to The Scientist. Whether the newly identified Post too long. Click here to view the full text.