Do Biofilm Formation and Interactions with Human Cells Explain the Clinical Success of Acinetobacter baumannii?

BACKGROUND: The dramatic increase in antibiotic resistance and the recent manifestation in war trauma patients underscore the threat of Acinetobacter baumannii as a nosocomial pathogen. Despite numerous reports documenting its epidemicity, little is known about the pathogenicity of A. baumannii. The aim of this study was to obtain insight into the factors that might explain the clinical success of A. baumannii. METHODOLOGY/PRINCIPAL FINDINGS: We compared biofilm formation, adherence to and inflammatory cytokine induction by human cells for a large panel of well-described strains of A. baumannii and compared these features to that of other, clinically less relevant Acinetobacter species. Results revealed that biofilm formation and adherence to airway epithelial cells varied widely within the various species, but did not differ among the species. However, airway epithelial cells and cultured human macrophages produced significantly less inflammatory cytokines upon exposure to A. baumannii strains than to strains of A. junii, a species infrequently causing infection. CONCLUSION/SIGNIFICANCE: The induction of a weak inflammatory response may provide a clue to the persistence of A. baumannii in patients

The Heat Shock Genes dnaK, dnaJ, and grpE Are Involved in Regulation of Putisolvin Biosynthesis in Pseudomonas putida PCL1445

Pseudomonas putida PCL1445 produces two cyclic lipopeptides, putisolvins I and II, which possess surfactant activity and play an important role in biofilm formation and degradation. In order to identify genes and traits that are involved in the regulation of putisolvin production of PCL1445, a Tn5luxAB library was generated and mutants were selected for the lack of biosurfactant production using a drop-collapsing assay. Sequence analysis of the Tn5luxAB flanking region of one biosurfactant mutant, strain PCL1627, showed that the transposon had inserted in a dnaK homologue which is located downstream of grpE and upstream of dnaJ. Analysis of putisolvin production and expression studies indicate that dnaK, together with the dnaJ and grpE heat shock genes, takes part in the positive regulation (directly or indirectly) of putisolvin biosynthesis at the transcriptional level. Growth of PCL1445 at low temperature resulted in an increased level of putisolvins, and mutant analyses showed that this requires dnaK and dnaJ but not grpE. In addition, putisolvin biosynthesis of PCL1445 was found to be dependent on the GacA/GacS two-component signaling system. Expression analysis indicated that dnaK is positively regulated by GacA/GacS

ANTIMICROBIAL EFFECTS OF INDONESIAN MEDICINAL PLANTS EXTRACTS ON PLANKTONIC AND BIOFILM GROWTH OF PSEUDOMONAS AERUGINOSA AND STAPHYLOCOCCUS AUREUS

Objective: The increasing rates of antibiotic-resistant microbial infections requires continuous development of new antimicrobial agents. Moreover, microbial biofilms exhibit elevated resistance to most antimicrobial drugs and the host defense systems, which often results in persistent and difficult-to-treat infections. The discovery of anti-infective agents which are active against both planktonic and biofilm microbial are consequently required to deal with these biofilm-mediated infections. The aim of this study is to evaluate the activity of Indonesian medicinal plants extracts on planktonic and biofilm growth of Pseudomonas aeruginosa PAO1 and Staphylococcus aureus Cowan I.Methods: Fifty four (54) ethanol extracts were obtained from a variety of known Indonesian medicinal plants. The growth inhibitory concentration (MIC), effects on biofilm formation and biofilm breakdown, and biofilm architecture in the absence and presence of the extracts by confocal laser-scanning microscopy along with LIVE/DEAD staining was performed.Results: Plantextracts showed an inhibitory effect on planktonic growth of these bacteria and also on their biofilm formation. At a concentration as low as 0.12 mg/ml, biofilm formation of P. aeruginosa PAO1 and S. aureus Cowan I is inhibited by 5 plant ethanol extracts: Kaempferia rotunda L., Caesalpinia sappan L., Cinnamomum burmanii Nees ex Bl., C. sintoc and Nymphaea nouchali Burm. f. Limited bacteriostatic activity was evident.Conclusion: The results clearly indicate the extracts obtained are interesting sources of putative antibiofilm agents. This research can contribute to the development of new strategies to prevent and treat biofilm infections

Problems and Promises of Introducing the Magnetic Resonance Imaging Linear Accelerator Into Routine Care: The Case of Prostate Cancer

The new radiotherapy high field, 1.5 Tesla MRI-guided linear accelerator (MR-Linac) is being clinically introduced. Sensing and evaluating opportunities and barriers at an early stage will facilitate its eventual scale-up. This study investigates the opportunities and barriers to the implementation of MR-Linac into prostate cancer care based on 43 semi-structured interviews with Dutch oncology care professionals, hospital and division directors, patients, payers and industry. The analysis was guided by the Non-adoption, Abandonment, Scale-up, Spread, and Sustainability framework of new medical technologies and services. Opportunities included: the acquirement of (1) advanced MRI-guided radiotherapy technology with (2) the potential for improved patient outcomes and (3) economic benefits, as well as (4) professional development and (5) a higher hospital quality profile. Barriers included: (1) technical complexities, (2) substantial staffing and structural investments, (3) the current lack of empirical evidence of clinical benefits, (4) professional silos, and (5) the presence of patient referral patterns. While our study confirms the expected technical and clinical prospects from the literature, it also reveals economic, organizational, and socio-political challenges

Additional file 1: Figure S1. of Identification and functional analysis of two Golgi-localized UDP-galactofuranose transporters with overlapping functions in Aspergillus niger

Homology tree of UgtA and UgtB homologs in Aspergilli. Protein sequence homologous to A. niger UgtA or A. niger UgtB were extracted from the AspGD database and aligned using DNAman. % of amino acid identity is given. (PPTX 303 kb

Problems and Promises of Introducing the Magnetic Resonance Imaging Linear Accelerator Into Routine Care: The Case of Prostate Cancer

The new radiotherapy high field, 1.5 Tesla MRI-guided linear accelerator (MR-Linac) is being clinically introduced. Sensing and evaluating opportunities and barriers at an early stage will facilitate its eventual scale-up. This study investigates the opportunities and barriers to the implementation of MR-Linac into prostate cancer care based on 43 semi-structured interviews with Dutch oncology care professionals, hospital and division directors, patients, payers and industry. The analysis was guided by the Non-adoption, Abandonment, Scale-up, Spread, and Sustainability framework of new medical technologies and services. Opportunities included: the acquirement of (1) advanced MRI-guided radiotherapy technology with (2) the potential for improved patient outcomes and (3) economic benefits, as well as (4) professional development and (5) a higher hospital quality profile. Barriers included: (1) technical complexities, (2) substantial staffing and structural investments, (3) the current lack of empirical evidence of clinical benefits, (4) professional silos, and (5) the presence of patient referral patterns. While our study confirms the expected technical and clinical prospects from the literature, it also reveals economic, organizational, and socio-political challenges

Maggot excretions/secretions are differentially effective against biofilms of Staphylococcus aureus and Pseudomonas aeruginosa

Objectives: Lucilia sericata maggots are successfully used for treating chronic wounds. As the healing process in these wounds is complicated by bacteria, particularly when residing in biofilms that protect them from antibiotics and the immune system, we assessed the effects of maggot excretions/secretions (ES) on Staphylococcus aureus and Pseudomonas aeruginosa biofilms, the clinically most relevant species. Methods: We assessed the effects of ES on biofilms using microtitre plate assays, on bacterial viability using in vitro killing and radial diffusion assays, and on quorum sensing systems using specific reporter bacteria. Results: As little as 0.2 μg of ES prevented S. aureus biofilm formation and 2 μg of ES rapidly degraded biofilms. In contrast, ES initially promoted P. aeruginosa biofilm formation, but after 10 h the biofilms collapsed. Degradation of P. aeruginosa biofilms started after 10 h and required 10-fold more ES than S. aureus biofilms. Boiling of ES abrogated their effects on S. aureus, but not on P. aeruginosa, biofilms, indicating that different molecules within ES are responsible for the observed effects. Modulation of biofilms by ES did not involve bacterial killing or effects on quorum sensing systems. Conclusions: Maggot ES are differentially effective against biofilms of S. aureus and P. aeruginosa