Modified virulence of antibiotic-induced Burkholderia pseudomallei filaments

Melioidosis is a life-threatening bacterial infection caused by Burkholderia. pseadomallei. Some antibiotics used to treat melioidosis can induce filamentation in B. pseudomallei. Despite studies on the mechanism of virulence of the bacteria, the properties of B. pseudomallei filaments and their impact on virulence have not been investigated before. To understand the characteristics of antibiotic-induced filaments, we performed in vitro assays to compare several aspects of virulence between normal, nonfilamentous and filamentous B. pseudotnallei. Normal, nonfilamentous B. pseudomallei could cause the lysis of monocytic cells, while filaments induced by sublethal concentrations of ceftazidime, ofloxacin, or trimethoprim show decreased lysis of monocytic cells, especially after prolonged antibiotic exposure. The motility of the filamentous bacteria was reduced compared to that of nonfilamentous bacteria. However, the filamentation was reversible when the antibiotics were removed, and the revertant bacteria recovered their motility and ability to lyse monocytic cells. Meanwhile, antibiotic resistance developed in revertant bacteria exposed to ceftazidime at the MIC. Our study highlights the danger of letting antibiotic concentration drop to the MIC or sub-MICs during antibiotic treatment of melioidosis. This could potentially give rise to a temporary reduction of bacterial virulence, only to result in bacteria that are equally virulent but more resistant to antibiotics, should the antibiotics be reduced or removed.