Abstract
Background Burkholderia pseudomallei, a Gram-negative bacterium that causes melioidosis, was reported to produce biofilm. As the disease causes high relapse rate when compared to other bacterial infections, it therefore might be due to the reactivation of the biofilm forming bacteria which also provided resistance to antimicrobial agents. However, the mechanism on how biofilm can provide tolerance to antimicrobials is still unclear.Methodology/Principal FindingsThe change in resistance of B. pseudomallei to doxycycline, ceftazidime, imipenem, and trimethoprim/sulfamethoxazole during biofilm formation were measured as minimum biofilm elimination concentration (MBEC) in 50 soil and clinical isolates and also in capsule, flagellin, LPS and biofilm mutants. Almost all planktonic isolates were susceptible to all agents studied. In contrast, when they were grown in the condition that induced biofilm formation, they were markedly resistant to all antimicrobial agents even though the amount of biofilm production was not the same. The capsule and O-side chains of LPS mutants had no effect on biofilm formation whereas the flagellin-defective mutant markedly reduced in biofilm production. No alteration of LPS profiles was observed when susceptible form was changed to resistance. The higher amount of N-acyl homoserine lactones (AHLs) was detected in the high biofilm-producing isolates. Interestingly, the biofilm mutant which produced a very low amount of biofilm and was sensitive to antimicrobial agents significantly resisted those agents when grown in biofilm inducing condition.Conclusions/SignificanceThe possible drug resistance mechanism of biofilm mutants and other isolates is not by having biofilm but rather from some factors that up-regulated when biofilm formation genes were stimulated. The understanding of genes related to this situation may lead us to prevent B. pseudomallei biofilms leading to the relapse of melioidosis.
Highlights
Melioidosis is the disease caused by gram negative bacterium, Burkholderia pseudomallei
Melioidosis is still a serious infectious disease that requires a long course of antimicrobial therapy such as intravenous CTZ or carbapenems for at least 10 days, followed by oral antimicrobial agents, DOX, TMP/SMX or combination therapy for at least 12 weeks [20]
The role of biofilms in protecting B. pseudomallei against antimicrobial agents has been reported in one study using a modified Robbins device [21]
Summary
Melioidosis is the disease caused by gram negative bacterium, Burkholderia pseudomallei. In Thailand, the disease accounts for 20% of all community-acquired septicemias and the most common cause of the high mortality is septic shock [1,2]. B. pseudomallei is intrinsically resistant to many antimicrobial agents including first and second generations of cephalosporins, penicillins, macrolides, colistin, rifamycins, and aminoglycosides [3,4]. Burkholderia pseudomallei, a Gram-negative bacterium that causes melioidosis, was reported to produce biofilm. As the disease causes high relapse rate when compared to other bacterial infections, it might be due to the reactivation of the biofilm forming bacteria which provided resistance to antimicrobial agents. The mechanism on how biofilm can provide tolerance to antimicrobials is still unclear
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