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Journal of Bacteriology Jan 2022Stenotrophomonas maltophilia has recently arisen as a prominent nosocomial pathogen because of its high antimicrobial resistance and ability to cause chronic respiratory...
Stenotrophomonas maltophilia has recently arisen as a prominent nosocomial pathogen because of its high antimicrobial resistance and ability to cause chronic respiratory infections. Often the infections are worsened by biofilm formation which enhances antibiotic tolerance. We have previously found that mutation of the gene, encoding the glycolytic enzyme phosphoglycerate mutase, impacts the formation of this biofilm on biotic and abiotic surfaces at early time points. This finding, indicating an association between carbon source and biofilm formation, led us to hypothesize that metabolism would influence S. maltophilia biofilm formation and planktonic growth. In the present study, we tested the impact of various growth substrates on biofilm levels and growth kinetics to determine metabolic requirements for these processes. We found that S. maltophilia wild type preferred amino acids versus glucose for planktonic and biofilm growth and that deletion inhibited growth in amino acids. Furthermore, supplementation of the Δ strain by glucose or ribose phenotypically complemented growth defects. These results suggest that S. maltophilia shuttles amino acid carbon through gluconeogenesis to an undefined metabolic pathway supporting planktonic and biofilm growth. Further evaluation of these metabolic pathways might reveal novel metabolic activities of this pathogen. Stenotrophomonas maltophilia is a prominent opportunistic pathogen that often forms biofilms during infection. However, the molecular mechanisms of virulence and biofilm formation are poorly understood. The glycolytic enzyme phosphoglycerate mutase appears to play a role in biofilm formation, and we used a mutant in its gene () to probe the metabolic circuitry potentially involved in biofilm development. The results of our study indicate that S. maltophilia displays unique metabolic activities, which could be exploited for inhibiting growth and biofilm formation of this pathogen.
Topics: Amino Acids; Bacterial Proteins; Biofilms; Culture Media; Gene Expression Regulation, Bacterial; Metabolic Networks and Pathways; Ribose; Stenotrophomonas maltophilia
PubMed: 34633868
DOI: 10.1128/JB.00398-21 -
Antimicrobial Resistance and Infection... Jan 2021Stenotrophomonas maltophilia (S. maltophilia) is an opportunistic and nosocomial pathogen that can cause an invasive and fatal infection, particularly in hospitalized...
PURPOSE
Stenotrophomonas maltophilia (S. maltophilia) is an opportunistic and nosocomial pathogen that can cause an invasive and fatal infection, particularly in hospitalized and immunocompromised patients. However, little is known about the impact of S. maltophilia bacteremia in pediatric patients. Therefore, we aimed to identify risk factors for mortality, antibiotics susceptibility to S. maltophilia, and mortality rates in pediatric patients with S. maltophilia bacteremia.
METHODS
We conducted a retrospective cohort study by identifying all S. maltophilia positive blood cultures in the microbiology laboratory database between January 2007 and December 2018 from hospitalized pediatric patients (age 1-14 years). After identifying patients with S. maltophilia bacteremia, medical charts were reviewed for demographics, clinical data, and outcomes within seven days of bacteremia diagnosis. Risk factors associated with mortality in S. maltophilia bacteremia patients were determined using univariate and multivariate analyses.
FINDINGS
Sixty-eight pediatric patients with S. maltophilia bacteremia were identified. All infections were nosocomial infections, and (88.2%) bacteremia cases were catheter-related bloodstream infections. On multivariate analysis, ICU admission prior to bacteremia episode and neutropenia were the major risk factors associated with mortality. S. maltophilia was the most susceptible to trimethoprim and sulfamethoxazole (TMP/SMX, 94.1%), followed by levofloxacin (85.7%). The overall mortality rate within seven days of S. maltophilia bacteremia diagnosis was 33.8%.
CONCLUSION
S. maltophilia bacteremia is a devastating emerging infection associated with high mortality among hospitalized children. Therefore, early diagnosis and prompt management based on local susceptibility data are crucial. Various risk factors, especially ICU admission prior to bacteremia episode and neutropenia, are associated with S. maltophilia bacteremia mortality.
Topics: Adolescent; Anti-Bacterial Agents; Catheter-Related Infections; Child; Child, Preschool; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Infant; Intensive Care Units; Male; Microbial Sensitivity Tests; Neutropenia; Retrospective Studies; Risk Factors; Saudi Arabia; Stenotrophomonas maltophilia
PubMed: 33482916
DOI: 10.1186/s13756-021-00888-w -
Microbiology Spectrum Aug 2023Stenotrophomonas maltophilia is increasingly recognized as an important nosocomial pathogen among the Gram-negative bacteria. Intrinsic resistance to different classes...
Stenotrophomonas maltophilia is increasingly recognized as an important nosocomial pathogen among the Gram-negative bacteria. Intrinsic resistance to different classes of antibiotics makes treatment of infections challenging. A deeper understanding of S. maltophilia physiology and virulence requires molecular genetic tools. Here, we describe the implementation of tetracycline-dependent gene regulation ( regulation) in this bacterium. The exploited regulatory sequence of transposon Tn contained the gene and three intertwined promoters, one of which was required for regulated expression of a target gene or operon. The episomal architecture was tested with a variant as a quantifiable reporter. Fluorescence intensity was directly correlated with the concentration of the inducer anhydrotetracycline (ATc) applied and the duration of induction. Also, the expression of the operon of S. maltophilia K279a was subjected to control. These genes code for the synthesis of dTDP-l-rhamnose, an activated nucleotide sugar precursor of lipopolysaccharide (LPS) formation. A Δ mutant was complemented with a plasmid carrying this operon downstream of the sequence. In the presence of ATc, the LPS pattern was similar to that of wild-type S. maltophilia, whereas without the inducer, fewer and apparently shorter O-antigen chains were detected. This underscores the functionality and usefulness of the system for gene regulation and, prospectively, the validation of targets for new anti-S. maltophilia drugs. Stenotrophomonas maltophilia is an emerging pathogen in hospital settings and poses a threat to immunocompromised patients. Due to a high level of resistance to different types of antibiotics, treatment options are limited. We here adapted a tool for inducible expression of genes of interest, known as the system, to S. maltophilia. Genes relevant to producing surface carbohydrate structures (lipopolysaccharide [LPS]) were placed under the control of the system. In the presence of an inducer, the LPS pattern was similar to that of wild-type S. maltophilia, whereas in the "off" state of the system (without inducer), fewer and apparently shorter versions of LPS were detected. The system is functional in S. maltophilia and may be helpful to reveal gene-function relationships to gain a deeper understanding of the bacterium's physiology and virulence.
Topics: Humans; Stenotrophomonas maltophilia; Lipopolysaccharides; Anti-Bacterial Agents; Gene Expression
PubMed: 37378537
DOI: 10.1128/spectrum.01576-23 -
Journal of Medical Microbiology Jan 2021has emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has...
has emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has not been fully established. Sequential isolates of from a Brazilian adult patient are clonally related and show a pattern of adaptation by loss of virulence factors. To investigate antimicrobial susceptibility, clonal relatedness, mutation frequency, quorum sensing (QS) and selected virulence factors in sequential isolates from a Brazilian adult patient attending a CF referral centre in Buenos Aires, Argentina, between May 2014 and May 2018. The antibiotic resistance of 11 S. isolates recovered from expectorations of an adult female with CF was determined. Clonal relatedness, mutation frequency, QS variants (RpfC-RpfF), QS autoinducer (DSF) and virulence factors were investigated in eight viable isolates. Seven isolates were resistant to trimethoprim-sulfamethoxazole and five to levofloxacin. All isolates were susceptible to minocycline. Strong, weak and normomutators were detected, with a tendency to decreased mutation rate over time. PFGE revealed that seven isolates belong to two related clones. All isolates were RpfC-RpfF1 variants and DSF producers. Only two isolates produced weak biofilms, but none displayed swimming or twitching motility. Four isolates showed proteolytic activity and amplified and genes. Only the first three isolates were siderophore producers. Four isolates showed high resistance to oxidative stress, while the last four showed moderate resistance. The present study shows the long-time persistence of two related clones in an adult female with CF. During the adaptation of the prevalent clones to the CF lungs over time, we identified a gradual loss of virulence factors that could be associated with the high amounts of DSF produced by the evolved isolates. Further, a decreased mutation rate was observed in the late isolates. The role of all these adaptations over time remains to be elucidated from a clinical perspective, probably focusing on the damage they can cause to CF lungs.
Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; Cystic Fibrosis; Drug Resistance, Bacterial; Female; Genotype; Gram-Negative Bacterial Infections; Humans; Lung; Male; Mutation; Phenotype; Phylogeny; Sputum; Stenotrophomonas maltophilia; Young Adult
PubMed: 33258754
DOI: 10.1099/jmm.0.001281 -
Anatolian Journal of Cardiology Dec 2017
Topics: Aged; Diagnosis, Differential; Echocardiography; Gram-Negative Bacterial Infections; Humans; Lung Neoplasms; Male; Pericarditis; Stenotrophomonas maltophilia
PubMed: 29256885
DOI: 10.14744/AnatolJCardiol.2017.8024 -
Frontiers in Cellular and Infection... 2018is an opportunistic Gram-negative pathogen with increasing incidence in clinical settings. The most critical aspect of is its frequent resistance to a majority of the... (Review)
Review
is an opportunistic Gram-negative pathogen with increasing incidence in clinical settings. The most critical aspect of is its frequent resistance to a majority of the antibiotics of clinical use. Quorum Sensing (QS) systems coordinate bacterial populations and act as major regulatory mechanisms of pathogenesis in both pure cultures and poly-microbial communities. Disruption of QS systems, a phenomenon known as Quorum Quenching (QQ), represents a new promising paradigm for the design of novel antimicrobial strategies. In this context, we review the main advances in the field of QS in by paying special attention to Diffusible Signal Factor (DSF) signaling, Acyl Homoserine Lactone (AHL) responses and the controversial Ax21 system. Advances in the DSF system include regulatory aspects of DSF synthesis and perception by both -1 and -2 variant systems, as well as their reciprocal communication. Interaction via DSF of with unrelated organisms including bacteria, yeast and plants is also considered. Finally, an overview of the different QQ mechanisms involving as quencher and as object of quenching is presented, revealing the potential of this species for use in QQ applications. This review provides a comprehensive snapshot of the interconnected QS network that uses to sense and respond to its surrounding biotic or abiotic environment. Understanding such cooperative and competitive communication mechanisms is essential for the design of effective anti QS strategies.
Topics: Acyl-Butyrolactones; Anti-Infective Agents; Bacterial Proteins; Cross Infection; Cytokines; Drug Resistance, Multiple, Bacterial; Quorum Sensing; Signal Transduction; Stenotrophomonas maltophilia
PubMed: 29740543
DOI: 10.3389/fcimb.2018.00122 -
Virus Genes Apr 2021Stenotrophomonas maltophilia (hereinafter referred to as S. maltophilia) has developed into an important opportunistic pathogenic bacterium, which is prevalent in...
Stenotrophomonas maltophilia (hereinafter referred to as S. maltophilia) has developed into an important opportunistic pathogenic bacterium, which is prevalent in nosocomial and community infections, and has adverse effects on patients with a compromised immune system. Phage vB_SmaS_BUCT548 was isolated from sewage of Beijing 307 Hospital with S. maltophilia (strain No.824) as a host. Phage morphology was observed by transmission electron microscopy and its biological and genomic characteristics were determined. The electron microscope shows that the bacteriophage belonged to the Siphoviridae and MOI is 0.001. One-step growth curve shows that the incubation period is 30 min and the burst size is 134 PFU/Cell. The host range is relatively wide and it can lysis 11of 13 S. maltophilia strains. Next-Generation Sequencing (NGS) results show that the genome sequence is a dsDNA with 62354 bp length, and the GC content is 56.3% (GenBank: MN937349). One hundred and two online reading frames (ORFs) are obtained after RAST online annotation and the BlastN nucleic acid comparison shows that the phage had low homology with other phages in NCBI database. This study reports a novel S. maltophilia phage named vB_SmaS_BUCT548, which has a short incubation period, strong lytic ability, and a wide host range. The main characteristic of this bacteriophage is the novelty of the genomic sequence and the analysis of the other characteristics provides basic data for further exploring the interaction mechanism between the phage and the host.
Topics: DNA, Viral; Genome, Viral; High-Throughput Nucleotide Sequencing; Host Specificity; Sequence Analysis, DNA; Sewage; Siphoviridae; Stenotrophomonas maltophilia
PubMed: 33471272
DOI: 10.1007/s11262-020-01818-5 -
Respiratory Medicine Mar 2022Little information is available about Stenotrophomonas maltophilia in patients with bronchiectasis. We analyzed data from the US Bronchiectasis and NTM Research Registry...
INTRODUCTION
Little information is available about Stenotrophomonas maltophilia in patients with bronchiectasis. We analyzed data from the US Bronchiectasis and NTM Research Registry to determine its prevalence and association with patient characteristics and severity of disease.
METHODS
Baseline and follow-up data were entered into a central web-based database. Patients were grouped into four cohorts based on their baseline cultures: 1) S. maltophilia, no Pseudomonas aeruginsosa, 2) P. aeruginosa, no S. maltophilia, 3) No pathogens, 4) Pathogens other than P. aeruginosa and S. maltophilia. The association between S. maltophilia, demographic characteristics, pulmonary function, exacerbations and hospitalizations was assessed at baseline and one year follow-up.
RESULTS
Among 2659 patients, 134 (5.0%) had grown S. maltophilia at baseline. The prior exacerbation rate at baseline was similar in patients with S. maltophilia and P. aeruginosa, but significantly higher than the other two groups. Hospitalizations were more frequent in patients with S. maltophilia or P. aeruginosa. Pre-bronchodilator FEV1 among S. maltophilia patients was between that of Pseudomonas patients and patients without either organism, but was not significantly different from any of the other groups. For all risk-adjusted one-year outcomes, patients with S. maltophilia had a non-significant trend towards worse outcomes compared to patients without P. aeruginosa, but were more similar to patients with P aeruginosa.
DISCUSSION
Bronchiectasis patients with S. maltophilia may have worse outcomes than patients without this organism or without P. aeruginosa; further study is needed to determine if the non-significant trends we note are clinically significant.
Topics: Bronchiectasis; Humans; Lung; Pseudomonas aeruginosa; Registries; Stenotrophomonas maltophilia
PubMed: 35124355
DOI: 10.1016/j.rmed.2022.106746 -
Expert Review of Anti-infective Therapy Nov 2019: Infections caused by the opportunistic pathogen in immunocompromised patients are complicated to treat due to antibiotic resistance and the ability of the bacteria to... (Review)
Review
: Infections caused by the opportunistic pathogen in immunocompromised patients are complicated to treat due to antibiotic resistance and the ability of the bacteria to produce biofilm.: A MEDLINE/PubMed search was performed of available literature to describe the role of biofilm produced by in the diseases it causes, including biofilm-influencing factors, the biofilm forming process and composition. The antimicrobial resistance due to biofilm production and current antibiofilm strategies is also included.: Through the production of biofilm, strains can easily adhere to the surfaces in hospital settings and aid in its transmission. The biofilm can also cause antibiotic tolerance rendering some of the therapeutic options ineffective, causing setbacks in the selection of an appropriate treatment. Conventional susceptibility tests do not yet offer therapeutic guidelines to treat biofilm-associated infections. Current biofilm control strategies include natural and synthetic compounds, chelating agents, and commonly prescribed antibiotics. As biofilm age and matrix composition affect the level of antibiotic tolerance, their characterization should be included in biofilm susceptibility testing, in addition to molecular and proteomic analyzes. As for now, several commonly recommended antibiotics can be used to treat biofilm-related infections.
Topics: Animals; Anti-Bacterial Agents; Biofilms; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Microbial Sensitivity Tests; Proteomics; Stenotrophomonas maltophilia
PubMed: 31658838
DOI: 10.1080/14787210.2019.1685875 -
Acta Crystallographica. Section F,... Jul 2023The resistance of the emerging human pathogen Stenotrophomonas maltophilia to tetracycline antibiotics mainly depends on multidrug efflux pumps and ribosomal protection...
The resistance of the emerging human pathogen Stenotrophomonas maltophilia to tetracycline antibiotics mainly depends on multidrug efflux pumps and ribosomal protection enzymes. However, the genomes of several strains of this Gram-negative bacterium code for a FAD-dependent monooxygenase (SmTetX) homologous to tetracycline destructases. This protein was recombinantly produced and its structure and function were investigated. Activity assays using SmTetX showed its ability to modify oxytetracycline with a catalytic rate comparable to those of other destructases. SmTetX shares its fold with the tetracycline destructase TetX from Bacteroides thetaiotaomicron; however, its active site possesses an aromatic region that is unique in this enzyme family. A docking study confirmed tetracycline and its analogues to be the preferred binders amongst various classes of antibiotics.
Topics: Humans; Stenotrophomonas maltophilia; Crystallography, X-Ray; Anti-Bacterial Agents; Tetracycline; Oxytetracycline; Microbial Sensitivity Tests
PubMed: 37405486
DOI: 10.1107/S2053230X23005381