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Published on: October 15, 2013
Modified virulence of antibiotic-induced Burkholderia pseudomallei filaments
Kang Chen1, Guang Wen Sun, Kim Lee Chua
1Department of Biochemistry, National University of Singapore, 8 Medical Dr., Singapore 117597, Singapore.
Abstract:
Melioidosis is a life-threatening bacterial infection caused by Burkholderia pseudomallei. 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. pseudomallei. 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.
Insights
Antibiotic treatment for melioidosis can cause dangerous bacterial filamentation. This temporary reduction in virulence may lead to more resistant bacteria upon antibiotic withdrawal.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Melioidosis, a severe infection caused by Burkholderia pseudomallei, is treated with antibiotics.
- Certain antibiotics can induce filamentation in B. pseudomallei.
- The impact of B. pseudomallei filamentation on virulence remains poorly understood.
Purpose of the Study:
- To investigate the characteristics of antibiotic-induced B. pseudomallei filaments.
- To compare the virulence of filamentous and nonfilamentous B. pseudomallei in vitro.
- To assess the reversibility of filamentation and potential development of antibiotic resistance.
Main Methods:
- In vitro assays comparing normal and filamentous B. pseudomallei.
- Induction of filamentation using sublethal concentrations of ceftazidime, ofloxacin, and trimethoprim.
- Assessment of monocytic cell lysis, bacterial motility, and antibiotic resistance.
Main Results:
- Filamentous B. pseudomallei showed reduced ability to lyse monocytic cells compared to nonfilamentous forms.
- Bacterial motility was decreased in filamentous bacteria.
- Filamentation was reversible upon antibiotic removal, with recovery of virulence and motility.
- Revertant bacteria exposed to ceftazidime at the minimum inhibitory concentration (MIC) developed antibiotic resistance.
Conclusions:
- Antibiotic-induced filamentation of B. pseudomallei can temporarily decrease virulence.
- Sub-MIC antibiotic concentrations during melioidosis treatment pose a risk.
- This can lead to the emergence of more virulent and antibiotic-resistant bacterial strains.
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