Dataset Information

Inactivation of Lytic Transglycosylases Increases Susceptibility to Aminoglycosides and Macrolides by Altering the Outer Membrane Permeability of Stenotrophomonas maltophilia.

ABSTRACT: Stenotrophomonas maltophilia harbors six lytic transglycosylases (LTs): mltA, mltB1, mltB2, mltD1, mltD2, and slt LT deletion increased susceptibility of S. maltophilia to aminoglycosides (AGs) and macrolides, and the underlying mechanisms were investigated. The expression of AG-modifying enzymes and efflux pumps was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Susceptibility to 1-N-phenylnaphthylamine, vancomycin, SDS, and bile salts was measured to assess outer membrane permeability. In conclusion, increased outer membrane permeability contributes to LT deletion-mediated increase in aminoglycoside and macrolide susceptibility.

SUBMITTER: Wu CJ

PROVIDER: S-EPMC4862486 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Inactivation of Lytic Transglycosylases Increases Susceptibility to Aminoglycosides and Macrolides by Altering the Outer Membrane Permeability of Stenotrophomonas maltophilia.

Wu Chao-Jung CJ Huang Yi-Wei YW Lin Yi-Tsung YT Yang Tsuey-Ching TC

Antimicrobial agents and chemotherapy 20160422 5

Stenotrophomonas maltophilia harbors six lytic transglycosylases (LTs): mltA, mltB1, mltB2, mltD1, mltD2, and slt LT deletion increased susceptibility of S. maltophilia to aminoglycosides (AGs) and macrolides, and the underlying mechanisms were investigated. The expression of AG-modifying enzymes and efflux pumps was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Susceptibility to 1-N-phenylnaphthylamine, vancomycin, SDS, and bile salts was measured to assess outer membrane perme ...[more]

PMID: 26976867

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Project description:BackgroundStenotrophomonas maltophilia (S. maltophilia) is an emerging global multiple-drug-resistant organism. It becomes increasingly challenging to treat S. maltophilia infection effectively. Novel therapeutic and preventive approaches targeting S. maltophilia infection are still lacking. This study aims to isolate outer membrane proteins (Omps) from S. maltophilia and use immunoproteomic technology to identify potential vaccine candidates of Omps against S. maltophilia infections.MethodsOmps from S. maltophilia culture were separated by two-dimensional electrophoresis and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry and nano liquid chromatography coupled fourier transform ion cyclotron resonance tandem mass spectrometry. Recombinant Omps were prepared and used to immunize mice, and the potency of mouse anti-Omp serum was tested in opsonophagocytic killing assay (OPKA). The effects of immunization with recombinant Omp on blood and tissue bacterial loads in a mouse model of S. maltophilia-induced infection were analyzed.ResultsOuter membrane protein A (OmpA) and Smlt4123 were identified by mass spectrometry. Mouse anti-Smlt4123 serum significantly reduced the bacterial counts in healthy individuals' blood in OPKA (P < 0.05) but mouse anti-OmpA serum did not. Enzyme-linked immunosorbent assay revealed that the antibody subtype of mouse anti-Smlt4123 antibody was IgG1. Eight hours after an intraperitoneal challenge with S. maltophilia, the bacterial loads in mouse blood were significantly lower in the mice receiving immunization with recombinant Smlt4123 than in the control mice receiving no immunization (P < 0.05), whereas the bacterial loads in other organs, such as the liver, spleen, lung, and kidney were similar in the two groups.ConclusionsThe results revealed that the immunoproteomic approach was an efficient way to screen the immunogenic protein of Stenotrophomonas maltophilia. Moreover, the recombinant Smlt4123 had potential to protect mice from bacteremia caused by S. maltophilia in the early stages.

Dataset Information

Inactivation of Lytic Transglycosylases Increases Susceptibility to Aminoglycosides and Macrolides by Altering the Outer Membrane Permeability of Stenotrophomonas maltophilia.

Publications

Inactivation of Lytic Transglycosylases Increases Susceptibility to Aminoglycosides and Macrolides by Altering the Outer Membrane Permeability of Stenotrophomonas maltophilia.

Similar Datasets

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