RESUMO
Stenotrophomonas maltophilia intrinsic resistance to ß-lactams is mediated by two chromosomal ß-lactamases, L1 and L2, whose induction depends on AmpR. Its quorum sensing (QS) signal, the diffusible signal factor (DSF), has a positive role in biofilm production, virulence and induction of ß-lactamases. We hypothesized that AmpR has a role in virulence, biofilm production and QS system. Studies were done on S. maltophilia K279a, K279a ampRFS (ampR deficient mutant) and K279aM11 (constitutively active AmpR mutant). K279a ampRFS showed the highest biofilm biomass, thickness and 3D organization. Conversely, K279aM11 was the least efficient biofilm former strain. qRT-PCR showed that spgM, related to biofilm formation and virulence, was upregulated in K279a ampRFS and downregulated in K279aM11. A constitutively active AmpR led to a reduction of DSF production, while K279a ampRFS was the highest producer. Consequently, qRT-PCR showed that AmpR negatively regulated rpfF expression. K279a ampRFS presented the highest oxidative stress resistance, overexpressed sodA gene and showed the highest virulence in the Galleria mellonella killing assay. This is the first evidence of the function of AmpR as a dual regulator in S. maltophilia with a positive role in ß-lactam resistance and a negative role in DSF production, biofilm formation, oxidative stress resistance and virulence.
Assuntos
Stenotrophomonas maltophilia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes , Stenotrophomonas maltophilia/genética , Virulência , Resistência beta-Lactâmica/genética , beta-Lactamases/genéticaRESUMO
HTLV-1 proviral load (pVL) in peripheral blood mononuclear cell (PBMCs) is proposed as a marker of disease progression but its role still remains controversial. The aim of this study was to evaluate the levels of HTLV-1 pVL in symptomatic patients and asymptomatic HTLV-1 carriers. In this cross-sectional study the pVL was measured by Real Time PCR in 102 asymptomatic carriers and 22 symptomatic patients (5ATLL, 15 TSP and 2 uveitis). We observed that the HTLV-1 pVL was significantly higher in symptomatic patients (median = 4.99 log10 HTLV-1 copies /106 PBMCs) compared to asymptomatic HTLV-1 carriers (median = 4.38 log10 HTLV-1 copies /106 PBMCs; p = 0.0030). A wide variation on the HTLV-1 pVL levels among asymptomatic HTLV-1 carriers was observed with some pVL as high as those observed in symptomatic patients. The asymptomatic HTLV-1 carriers were divided according to the place of birth and the highest levels of pVL were detected among patients from endemics areas from the North of Argentina. Our results reinforce the usefulness of the proviral load would be a prognostic marker of HTLV-1 disease progression. Moreover, host, viral or socio-environmental factors cannot be excluded as determinant of high proviral load.