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PloS One 2021Stenotrophomonas maltophilia is a multidrug resistant pathogen associated with high mortality and morbidity in patients having compromised immunity. The efflux systems...
Stenotrophomonas maltophilia is a multidrug resistant pathogen associated with high mortality and morbidity in patients having compromised immunity. The efflux systems of S. maltophilia include SmeABC and SmeDEF proteins, which assist in acquisition of multiple-drug-resistance. In this study, proteome based mapping was utilized to find out the potential drug targets for S. maltophilia strain k279a. Various tools of computational biology were applied to remove the human-specific homologous and pathogen-specific paralogous sequences from the bacterial proteome. The CD-HIT analysis selected 4315 proteins from total proteome count of 4365 proteins. Geptop identified 407 essential proteins, while the BlastP revealed approximately 85 non-homologous proteins in the human genome. Moreover, metabolic pathway and subcellular location analysis were performed for essential bacterial genes, to describe their role in various cellular processes. Only two essential proteins (Acyl-[acyl-carrier-protein]-UDP-N acetyl glucosamine O-acyltransferase and D-alanine-D-alanine ligase) as candidate for potent targets were found in proteome of the pathogen, in order to design new drugs. An online tool, Swiss model was employed to model the 3D structures of both target proteins. A library of 5000 phytochemicals was docked against those proteins through the molecular operating environment (MOE). That resulted in to eight inhibitors for both proteins i.e. enterodiol, aloin, ononin and rhinacanthinF for the Acyl-[acyl-carrier-protein]-UDP-N acetyl glucosamine O-acyltransferase, and rhazin, alkannin beta, aloesin and ancistrocladine for the D-alanine-D-alanine ligase. Finally the ADMET was done through ADMETsar. This study supported the development of natural as well as cost-effective drugs against S. maltophilia. These inhibitors displayed the effective binding interactions and safe drug profiles. However, further in vivo and in vitro validation experiment might be performed to check their drug effectiveness, biocompatibility and their role as effective inhibitors.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Drug Delivery Systems; Models, Molecular; Molecular Docking Simulation; Protein Conformation; Proteome; Stenotrophomonas maltophilia; Subtractive Hybridization Techniques
PubMed: 34910751
DOI: 10.1371/journal.pone.0261111 -
Viruses Dec 2023mainly causes respiratory infections that are associated with a high mortality rate among immunocompromised patients. exhibits a high level of antibiotic resistance...
mainly causes respiratory infections that are associated with a high mortality rate among immunocompromised patients. exhibits a high level of antibiotic resistance and can form biofilms, which complicates the treatment of patients infected with this bacterium. Phages combined with antibiotics could be a promising treatment option. Currently, ~60 phages are known, and their effects on biofilm formation and antibiotic sensitivity require further examination. Bacteriophage StM171, which was isolated from hospital wastewater, showed a medium host range, low burst size, and low lytic activity. StM171 has a 44kbp dsDNA genome that encodes 59 open-reading frames. A comparative genomic analysis indicated that StM171, along with the phage Suso (MZ326866) and phage HXX_Dennis (ON711490), are members of a new putative genus. strains that developed resistance to StM171 (bacterial-insensitive mutants) showed a changed sensitivity to antibiotics compared to the originally susceptible strains. Some bacterial-insensitive mutants restored sensitivity to cephalosporin and penicillin-like antibiotics and became resistant to erythromycin. StM171 shows strain- and antibiotic-dependent effects on the biofilm formation of strains.
Topics: Humans; Anti-Bacterial Agents; Bacteriophages; Stenotrophomonas maltophilia; Biofilms
PubMed: 38140696
DOI: 10.3390/v15122455 -
Antimicrobial Agents and Chemotherapy Jul 2021Stenotrophomonas maltophilia bloodstream infections (BSI) are associated with considerable mortality in the hematologic malignancy population....
Stenotrophomonas maltophilia bloodstream infections (BSI) are associated with considerable mortality in the hematologic malignancy population. Trimethoprim-sulfamethoxazole (TMP-SMX) is the treatment of choice; however, it is not routinely included in empirical treatment regimens, both because of its adverse event profile and the relative rarity of S. maltophilia infections. We developed a risk score to predict hematologic malignancy patients at increased risk for S. maltophilia BSI to guide early (TMP-SMX) therapy. Patients ≥12 years of age admitted to five hospitals between July 2016 and December 2019 were included. Two separate risk scores were developed, (i) a "knowledge-driven" risk score based upon previously identified risk factors in the literature in addition to variables identified by regression analysis using the current cohort, and (ii) a risk score based upon automatic variable selection. For both scores, discrimination (receiver operator characteristic [ROC] curves and statistics) and calibration (Hosmer-Lemeshow goodness-of-fit test and graphical calibration plots) were assessed. Internal validation was assessed using leave-one-out cross-validation. In total, 337 unique patients were included; 21 (6.2%) had S. maltophilia BSI. The knowledge-driven risk score (acute leukemia, absolute neutrophil count category, mucositis, central line, and ≥3 days of carbapenem therapy) had superior performance ( statistic = 0.75; 0.71 after cross-validation) compared to that of the risk score utilizing automatic variable selection ( statistic = 0.63; 0.38 after cross-validation). A user-friendly risk score incorporating five variables easily accessible to clinicians performed moderately well to predict hematologic malignancy patients at increased risk for S. maltophilia BSI. External validation using a larger cohort is necessary to create a refined risk score before broad clinical application.
Topics: Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Retrospective Studies; Sepsis; Stenotrophomonas maltophilia
PubMed: 34060899
DOI: 10.1128/AAC.00793-21 -
Molecules (Basel, Switzerland) Oct 2017A group of flavones, isoflavones, flavanones, and chalcones was subjected to small-scale biotransformation studies with the Gram-negative KB2 strain in order to...
A group of flavones, isoflavones, flavanones, and chalcones was subjected to small-scale biotransformation studies with the Gram-negative KB2 strain in order to evaluate the capability of this strain to transform flavonoid compounds and to investigate the relationship between compound structure and transformation type. The tested strain transformed flavanones and chalcones. The main type of transformation of compounds with a flavanone moiety was central heterocyclic C ring cleavage, leading to chalcone and dihydrochalcone structures, whereas chalcones underwent reduction to dihydrochalcones and cyclisation to a benzo-γ-pyrone moiety. Substrates with a C-2-C-3 double bond (flavones and isoflavones) were not transformed by KB2.
Topics: Biotransformation; Chalcones; Flavanones; Magnetic Resonance Spectroscopy; Molecular Structure; Stenotrophomonas maltophilia
PubMed: 29077064
DOI: 10.3390/molecules22111830 -
Microbiology Spectrum Jun 2022Stenotrophomonas maltophilia is a multidrug-resistant human opportunistic pathogen. S. maltophilia contributes to disease progression in cystic fibrosis patients and is...
Stenotrophomonas maltophilia is a multidrug-resistant human opportunistic pathogen. S. maltophilia contributes to disease progression in cystic fibrosis patients and is found in wounds and infected tissues and on catheter surfaces. Due to its well-known multidrug resistance, it is difficult to treat S. maltophilia infections. Strain-specific susceptibility to antimicrobials has also been reported in several studies. Recently, three fungal diorcinols and 14 rubrolides were shown to reduce S. maltophilia K279a biofilm formation. Based on these initial findings, we were interested to extend this approach by testing a larger number of diorcinols and rubrolides and to understand the molecular mechanisms behind the observed antibiofilm effects. Of 52 tested compounds, 30 were able to significantly reduce the biofilm thickness by up to 85% ± 15% and had strong effects on mature biofilms. All compounds with antibiofilm activity also significantly affected the biofilm architecture. Additional RNA-sequencing data of diorcinol- and rubrolide-treated biofilm cells of two clinical isolates (454 and K279) identified a small set of shared genes that were affected by these potent antibiofilm compounds. Among these, genes for iron transport, general metabolism, and membrane biosynthesis were most strongly and differentially regulated. A further hierarchical clustering and detailed structural inspection of the diorcinols and rubrolides implied that a prenyl group as side chain of one of the phenyl groups of the diorcinols and an increasing degree of bromination of chlorinated rubrolides were possibly the cause of the strong antibiofilm effects. This study gives a deep insight into the effects of rubrolides and diorcinols on biofilms formed by the important global pathogen S. maltophilia. Combating Stenotrophomonas maltophilia biofilms in clinical and industrial settings has proven to be challenging. S. maltophilia is multidrug resistant, and occurrence of resistance to commonly used drugs as well as to antibiotic combinations, such as trimethoprim-sulfamethoxazole, is now frequently reported. It is therefore now necessary to look beyond conventional and already existing antimicrobial drugs when battling S. maltophilia biofilms. Our study contains comprehensive and detailed data sets for diorcinol and rubrolide-treated S. maltophilia biofilms. The study defines genes and pathways affected by treatment with these different compounds. These results, together with the identified structural elements that may be crucial for their antibiofilm activity, build a strong backbone for further research on diorcinols and rubrolides as novel and potent antibiofilm compounds.
Topics: Anti-Bacterial Agents; Biofilms; Gram-Negative Bacterial Infections; Humans; Stenotrophomonas maltophilia
PubMed: 35471093
DOI: 10.1128/spectrum.02582-21 -
The American Journal of Tropical... Dec 2020Patients undergoing hemodialysis are at an increased risk for bloodstream infections (BSIs). Infection usually occurs because of contamination of water supply, water...
Patients undergoing hemodialysis are at an increased risk for bloodstream infections (BSIs). Infection usually occurs because of contamination of water supply, water treatment, distribution systems, or reprocessing dialyzers. Here, we report an outbreak of BSIs caused by Stenotrophomonas maltophilia (n = 21) and Burkholderia cepacia (n = 22) among dialyzed patients at a large hemodialysis center in Brazil. Overall, three patients died (7%), two of which had bacteremia caused by S. maltophilia and the other had a B. cepacia infection. We collected water samples from different points of the hemodialysis system for culture and typing. Genetic patterns were identified through polymerase chain reaction-random amplified polymorphic DNA (PCR-RAPD) and pulsed-field gel electrophoresis. The same genotypes of S. maltophilia and B. cepacia recovered from blood cultures were found in dialysis water. Also, multiple genetic profiles were identified among water isolates, suggesting heavy contamination. Bacteremia cases persisted even after implementing standard control measures, which led us to believe that the piping system was contaminated with microbial biofilms. Soon after we changed the entire plumbing system, reported cases dropped back to the number typically expected, and the outbreak came to an end.
Topics: Adult; Aged; Aged, 80 and over; Brazil; Burkholderia Infections; Burkholderia cepacia; Disease Outbreaks; Disinfection; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Renal Dialysis; Sepsis; Stenotrophomonas maltophilia
PubMed: 33319730
DOI: 10.4269/ajtmh.20-1035 -
Respiratory Research Sep 2023The clinical significance of Stenotrophomonas maltophilia in patients with COPD is poorly understood. We aimed to determine whether a lower respiratory tract culture... (Observational Study)
Observational Study
OBJECTIVES
The clinical significance of Stenotrophomonas maltophilia in patients with COPD is poorly understood. We aimed to determine whether a lower respiratory tract culture positive for S. maltophilia in COPD patients was independently associated with increased risk of death and hospitalisation for exacerbation of COPD.
METHODS
An observational cohort study following outpatients with COPD in Eastern Denmark between 2010 and 2018, with a follow-up period of five years. Presence of S. maltophilia was treated as a time-varying exposure, where patients were considered exposed at the time of the first isolation of S. maltophilia from the lower respiratory tract. The hazard ratio (HR) of death and hospitalisation for acute exacerbations of COPD was assessed using a Cox proportional hazards regression.
RESULTS
Of the total 22,689 patients 459 (2.0%) had a lower respiratory sample positive for S. maltophilia. A total of 7,649 deaths (S. maltophilia positive: 243 (52.9%) and S. maltophilia negative: 7,406 (34.4%)) and 24,912 hospitalisations for exacerbation of COPD (S. maltophilia positive: 1,100 in 459 patients and S. maltophilia negative: 23,821 in 22,230 patients) were registered during the study period. We found that a lower respiratory tract culture positive for S. maltophilia was associated with both increased mortality: HR 3.3 (95% CI 2.6-4.3), and hospitalisation for exacerbation of COPD: HR 3.4 (95% CI 2.8-4.1).
CONCLUSIONS
A lower respiratory tract culture positive for S. maltophilia in COPD patients was associated with a substantially increased mortality and hospitalisation for exacerbation of COPD. Randomised controlled trials are proposed to determine whether S. maltophilia should be the target of antibiotic treatment.
Topics: Humans; Outpatients; Stenotrophomonas maltophilia; Cohort Studies; Clinical Relevance; Pulmonary Disease, Chronic Obstructive
PubMed: 37752596
DOI: 10.1186/s12931-023-02544-w -
Microbiology (Reading, England) Jul 2021Siderophores are produced by several bacteria that utilise iron in various environments. Elucidating the structure of a specific siderophore may have valuable...
Siderophores are produced by several bacteria that utilise iron in various environments. Elucidating the structure of a specific siderophore may have valuable applications in drug development. , a Gram-negative bacterium that inhabits a wide range of environments and can cause pneumonia, produces siderophores. However, the structure was unknown, and therefore, in this study, we aimed to elucidate it. We purified siderophores from cultures of K279a using preparative reversed-phase HPLC. The structure was analysed through LC-MS and H and C NMR. The results demonstrated that K279a produces 2,3-dihydroxybenzoylserine (DHBS), a monomer unit of enterobactin. We suggested the uptake of Iron(III) by the DHBS complex. DHBS production by K279a could be attributed to an incomplete enterobactin pathway. Drugs targeting DHBS synthesis could prevent infection.
Topics: Bacterial Proteins; Biological Transport; Chromatography, High Pressure Liquid; Iron; Magnetic Resonance Spectroscopy; Mass Spectrometry; Siderophores; Stenotrophomonas maltophilia
PubMed: 34280083
DOI: 10.1099/mic.0.001071 -
International Journal of Infectious... Aug 2012Stenotrophomonas maltophilia is a recently identified nosocomial pathogen in Malaysia. Despite limited pathogenicity, its rate of isolation has increased in recent...
OBJECTIVES
Stenotrophomonas maltophilia is a recently identified nosocomial pathogen in Malaysia. Despite limited pathogenicity, its rate of isolation has increased in recent years. The aim of this study was to investigate the antibiotic susceptibility patterns, antibiotic resistance determinants, and the epidemiology of S. maltophilia at the largest tertiary care hospital in Malaysia.
METHODS
This study was carried out from January to December 2008. Sixty-four S. maltophilia isolates were investigated for their antibiotic susceptibility patterns by disk diffusion test and E-test. The antibiotic resistance mechanism for trimethoprim-sulfamethoxazole (TMP-SMX) was assessed by PCR for sul1, sul2, qac/smr, and class 1 integrons in general. Epidemiological relatedness among isolates was determined by pulsed-field gel electrophoresis (PFGE).
RESULTS
The highest number of S. maltophilia infections was observed in the intensive care unit (ICU) (n=13; 20.3%), while the lowest number of infections was seen in the neurology, psychiatric, and dermatology wards (each n=1; 1.6%). All isolates were susceptible to minocycline. One isolate was resistant to TMP-SMX with a minimum inhibitory concentration (E-test) >32 mg/l. The strain carried the sul1 gene and class 1 integron. None of the isolates were positive for the qac/smr genes. Although the data suggest the potential for patient to patient transmission, most of the S. maltophilia strains showed unrelated PFGE patterns and were considered to be genetically diverse.
CONCLUSION
The increasing number of S. maltophilia isolates seen in the ICU, their resistance to mainstay antibiotics, their genetically diverse nature, and possible cross-transmission within the hospital, strongly underscores the need for continuous surveillance for S. maltophilia in the hospital setting.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Humans; Integrons; Malaysia; Phylogeny; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 22698885
DOI: 10.1016/j.ijid.2012.04.004 -
Microbes and Infection 2020Stenotrophomonas maltophilia biofilm formation is of increasing medical concern, particularly for lung infections. However, the molecular mechanisms facilitating the...
Stenotrophomonas maltophilia biofilm formation is of increasing medical concern, particularly for lung infections. However, the molecular mechanisms facilitating the biofilm lifestyle in S. maltophilia are poorly understood. We generated and screened a transposon mutant library for mutations that lead to altered biofilm formation compared to wild type. One of these mutations, in the gene for glycolytic enzyme phosphoglycerate mutase (gpmA), resulted in impaired attachment on abiotic and biotic surfaces. As adherence to a surface is the initial step in biofilm developmental processes, our results reveal a unique factor that could affect S. maltophilia biofilm initiation and, possibly, subsequent development.
Topics: Bacterial Adhesion; Bacterial Proteins; Biofilms; Cells, Cultured; Epithelial Cells; Humans; Mutation; Phosphoglycerate Mutase; Plastics; Stenotrophomonas maltophilia
PubMed: 31430538
DOI: 10.1016/j.micinf.2019.08.001