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.
Immunity induced by Plasmodium vivax infections leads to memory T-cell recruitment and activation during subsequent infections. Here, we investigated the role of regulatory T cells (Treg) in coordination with the host immune response during P. vivax infection. Our results showed a significant increase in the percentage of FOXP31 Treg, IL-10-secreting Type I Treg (Tr1) and IL-10 levels in patients with acute P. vivax infection as compared with those found in either naïve or immune controls. The concurrent increase in the Treg population could also be reproduced in vitro using peripheral blood mononuclear cells from naïve controls stimulated with crude antigens extracted from P. vivax-infected red blood cells. Acute P. vivax infections were associated with a significant decrease in the numbers of DC, indicating a general immunosuppression during P. vivax infections. However, unlike P. falciparum infections, we found that the ratio of myeloid DC (MDC) to plasmacytoid DC (PDC) was significantly lower in acute P. vivax patients than that of naïve and immune controls. Moreover, the reduction in PDC may be partly responsible for the poor antibody responses during P. vivax infections. Taken together, these results suggest that P. vivax parasites interact with DC, which alters the MDC/PDC ratio that potentially leads to Treg activation and IL-10 release.Key words: Dendritic cell . IL-10 . Malaria . Plasmodium vivax . Regulatory T cell Eur. J. Immunol. 2008. 38: 2697-2705 DOI 10.1002 Immunity to infection 2697 IntroductionMalaria is a common tropical disease causing deaths among Plasmodium falciparum-infected children mainly in Sub-Saharan Africa [1]. P. falciparum causes malignant tertian malaria that accounts for most malaria-associated deaths, whereas P. vivax causes relapsing fever and the infection rarely becomes fatal. Although a better understanding of immunity is needed for the design of effective vaccines, immune regulation in the host during malaria infection is not fully understood, and few studies have been conducted in patients with P. vivax infections. Our recent study has shown that anti-P. vivax antibody levels were very low in immune individuals living in endemic area and in patients with acute P. vivax malaria. For the cell-mediated arm, an acute P. vivax infection was associated with the activation of memory T cells belonging to either a cytotoxic or helper phenotype [2]. Additionally, previous evidence [3,4] shows that immunization with pre-erythrocytic antigens can induce IFN-g release. This suggests that P. vivax can activate the immune system via the Th1 pathway. However, a possible suppressing mechanism arises from the activation of regulatory T cells (Treg) as has been shown in a murine malaria study [5]. Treg constitutively express CD25, which is the IL-2/a chain receptor [6]. Co-presentation of CD25 with forkhead box protein P3 (FOXP3) dictates the immune-suppressive role of Treg via the release of . Treg have been shown to alter the balance between myeloid dendritic cells (MDC) and plasmacytoi...
The Burkholderia pseudomallei rpoS gene was identified, and an rpoS null mutant was constructed. The mutant was shown to have an increased sensitivity to carbon starvation and oxidative stress. By using rpoS-lacZ fusions, transcription of rpoS was shown to be growth phase regulated, reaching a peak upon entry into stationary phase.
Burkholderia pseudomallei is the causative agent of melioidosis, a fatal human tropical disease. The non-specific DNA-binding protein DpsA plays a key role in protecting B. pseudomallei from oxidative stress mediated, for example, by organic hydroperoxides. The regulation of dpsA expression is poorly understood but one possibility is that it is regulated in a cell population density-dependent manner via N-acylhomoserine lactone (AHL)-dependent quorum sensing (QS) since a lux-box motif has been located within the dpsA promoter region. Using liquid chromatography and tandem mass spectrometry, it was first established that B. pseudomallei strain PP844 synthesizes AHLs. These were identified as N-octanoylhomoserine lactone (C8-HSL), N-(3-oxooctanoyl)homoserine lactone (3-oxo-C8-HSL), N-(3-hydroxyoctanoyl)-homoserine lactone (3-hydroxy-C8-HSL), N-decanoylhomoserine lactone (C10-HSL), N-(3-hydroxydecanoyl) homoserine lactone (3-hydroxy-C10-HSL) and N-(3-hydroxydodecanoyl)homoserine lactone (3-hydroxy-C12-HSL). Mutation of the genes encoding the LuxI homologue BpsI or the LuxR homologue BpsR resulted in the loss of C8-HSL and 3-oxo-C8-HSL synthesis, demonstrating that BpsI was responsible for directing the synthesis of these AHLs only and that bpsI expression and hence C8-HSL and 3-oxo-C8-HSL production depends on BpsR. In bpsI, bpsR and bpsIR mutants, dpsA expression was substantially down-regulated. Furthermore, dpsA expression in Escherichia coli required both BpsR and C8-HSL. bpsIR-deficient mutants exhibited hypersensitivity to the organic hydroperoxide tert-butyl hydroperoxide by displaying a reduction in cell viability which was restored by provision of exogenous C8-HSL (bpsI mutant only), by complementation with the bpsIR genes or by overexpression of dpsA. These data indicate that in B. pseudomallei, QS regulates the response to oxidative stress at least in part via the BpsR/C8-HSL-dependent regulation of DpsA.
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