scholarly journals TonB‐dependent uptake of β‐lactam antibiotics in the opportunistic human pathogen Stenotrophomonas maltophilia

2019 ◽  
Vol 113 (2) ◽  
pp. 492-503 ◽  
Author(s):  
Karina Calvopiña ◽  
Punyawee Dulyayangkul ◽  
Kate J. Heesom ◽  
Matthew B. Avison
2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Kameron D. Garza ◽  
Heather Newkirk ◽  
Russell Moreland ◽  
Carlos F. Gonzalez ◽  
Mei Liu ◽  
...  

Stenotrophomonas maltophilia is an emerging opportunistic human pathogen. In this report, we describe the isolation and genomic annotation of the S. maltophilia-infecting bacteriophage Mendera. A myophage of 159,961 base pairs, Mendera is T4-like and related most closely to Stenotrophomonas phage IME-SM1.


2021 ◽  
Vol 7 (7) ◽  
Author(s):  
Prashant P. Patil ◽  
Sanjeet Kumar ◽  
Amandeep Kaur ◽  
Samriti Midha ◽  
Kanika Bansal ◽  
...  

Stenotrophomonas maltophilia is a typical example of an environmental originated opportunistic human pathogen, which can thrive at different habitats including the human body and can cause a wide range of infections. It must cope with heat stress during transition from the environment to the human body as the physiological temperature of the human body (37 °C) is higher than environmental niches (22–30 °C). Interestingly, S. rhizophila a phylogenetic neighbour of S. maltophilia within genus Stenotrophomonas is unable to grow at 37 °C. Thus, it is crucial to understand how S. maltophilia is adapted to human body temperature, which could suggest its evolution as an opportunistic human pathogen. In this study, we have performed comparative transcriptome analysis of S. maltophilia grown at 28 and 37 °C as temperature representative for environmental niches and the human body, respectively. RNA-Seq analysis revealed several interesting findings showing alterations in gene-expression levels at 28 and 37 °C, which can play an important role during infection. We have observed downregulation of genes involved in cellular motility, energy production and metabolism, replication and repair whereas upregulation of VirB/D4 type IV secretion system, aerotaxis, cation diffusion facilitator family transporter and LacI family transcriptional regulators at 37 °C. Microscopy and plate assays corroborated altered expression of genes involved in motility. The results obtained enhance our understanding of the strategies employed by S. maltophilia during adaptation towards the human body.


2019 ◽  
Author(s):  
Karina Calvopiña ◽  
Punyawee Dulyayangkul ◽  
Kate J. Heesom ◽  
Matthew B. Avison

AbstractThe β-lactam antibiotic ceftazidime is one of only a handful of drugs with proven clinical efficacy against the opportunistic human pathogen Stenotrophomonas maltophilia, Here, we show that mutations in the energy transducer TonB, encoded by smlt0009 in S. maltophilia, confer ceftazidime resistance. This breaks the dogma that β-lactams enter Gram-negative bacteria only by passive diffusion through outer membrane porins. By confirming cross-resistance of Smlt0009 mutants with a siderophore-conjugated lactivicin antibiotic, we reveal that attempts to improve penetration of antimicrobials into Gram negative bacteria by conjugating them with TonB substrates is likely to select β-lactam resistance in S. maltophilia, increasing its clinical threat. Furthermore, we show that S. maltophilia clinical isolates that have an Smlt0009 mutation already exist. Remarkably, therefore, β-lactam use is already eroding the potential utility of currently experimental siderophore-conjugated antimicrobials against this species.


2016 ◽  
Vol 4 (4) ◽  
Author(s):  
Josselin Bodilis ◽  
Benjamin Youenou ◽  
Jérome Briolay ◽  
Elisabeth Brothier ◽  
Sabine Favre-Bonté ◽  
...  

Stenotrophomonas maltophiliais a major opportunistic human pathogen responsible for nosocomial infections. Here, we report the draft genome sequences of Sm32COP, Sm41DVV, Sm46PAILV, SmF3, SmF22, SmSOFb1, and SmCVFa1, isolated from different manures in France, which provide insights into the genetic determinism of intrinsic or acquired antibiotic resistance in this species.


2012 ◽  
Vol 194 (21) ◽  
pp. 5864-5874 ◽  
Author(s):  
E. Roscetto ◽  
T. Angrisano ◽  
V. Costa ◽  
M. Casalino ◽  
K. U. Forstner ◽  
...  

2011 ◽  
Vol 77 (10) ◽  
pp. 3443-3450 ◽  
Author(s):  
Evelien M. Adriaenssens ◽  
Pieter-Jan Ceyssens ◽  
Vincent Dunon ◽  
Hans-Wolfgang Ackermann ◽  
Johan Van Vaerenbergh ◽  
...  

ABSTRACTPantoea agglomeransis a common soil bacterium used in the biocontrol of fungi and bacteria but is also an opportunistic human pathogen. It has been described extensively in this context, but knowledge of bacteriophages infecting this species is limited. Bacteriophages LIMEzero and LIMElight ofP. agglomeransare lytic phages, isolated from soil samples, belonging to thePodoviridaeand are the firstPantoeaphages of this family to be described. The double-stranded DNA (dsDNA) genomes (43,032 bp and 44,546 bp, respectively) encode 57 and 55 open reading frames (ORFs). Based on the presence of an RNA polymerase in their genomes and their overall genome architecture, these phages should be classified in the subfamily of theAutographivirinae, within the genus of the “phiKMV-like viruses.” Phylogenetic analysis of all the sequenced members of theAutographivirinaesupports the classification of phages LIMElight and LIMEzero as members of the “phiKMV-like viruses” and corroborates the subdivision into the different genera. These data expand the knowledge ofPantoeaphages and illustrate the wide host diversity of phages within the “phiKMV-like viruses.”


2019 ◽  
Vol 201 (13) ◽  
Author(s):  
Jelle Slager ◽  
Rieza Aprianto ◽  
Jan-Willem Veening

ABSTRACTCompetence for genetic transformation allows the opportunistic human pathogenStreptococcus pneumoniaeto take up exogenous DNA for incorporation into its own genome. This ability may account for the extraordinary genomic plasticity of this bacterium, leading to antigenic variation, vaccine escape, and the spread of antibiotic resistance. The competence system has been thoroughly studied, and its regulation is well understood. Additionally, over the last decade, several stress factors have been shown to trigger the competent state, leading to the activation of several stress response regulons. The arrival of next-generation sequencing techniques allowed us to update the competence regulon, the latest report on which still depended on DNA microarray technology. Enabled by the availability of an up-to-date genome annotation, including transcript boundaries, we assayed time-dependent expression of all annotated features in response to competence induction, were able to identify the affected promoters, and produced a more complete overview of the various regulons activated during the competence state. We show that 4% of all annotated genes are under direct control of competence regulators ComE and ComX, while the expression of a total of up to 17% of all genes is affected, either directly or indirectly. Among the affected genes are various small RNAs with an as-yet-unknown function. Besides the ComE and ComX regulons, we were also able to refine the CiaR, VraR (LiaR), and BlpR regulons, underlining the strength of combining transcriptome sequencing (RNA-seq) with a well-annotated genome.IMPORTANCEStreptococcus pneumoniaeis an opportunistic human pathogen responsible for over a million deaths every year. Although both vaccination programs and antibiotic therapies have been effective in prevention and treatment of pneumococcal infections, respectively, the sustainability of these solutions is uncertain. The pneumococcal genome is highly flexible, leading to vaccine escape and antibiotic resistance. This flexibility is predominantly facilitated by competence, a state allowing the cell to take up and integrate exogenous DNA. Thus, it is essential to obtain a detailed overview of gene expression during competence. This is stressed by the fact that administration of several classes of antibiotics can lead to competence. Previous studies on the competence regulon were performed with microarray technology and were limited to an incomplete set of known genes. Using RNA sequencing combined with an up-to-date genome annotation, we provide an updated overview of competence-regulated genes.


2018 ◽  
Vol 200 (16) ◽  
Author(s):  
Daniel M. Chodur ◽  
Dean A. Rowe-Magnus

ABSTRACT Vibrio vulnificus is a potent opportunistic human pathogen that contaminates the human food chain by asymptomatically colonizing seafood. The expression of the 9-gene brp exopolysaccharide locus mediates surface adherence and is controlled by the secondary signaling molecule c-di-GMP and the regulator BrpT. Here, we show that c-di-GMP and BrpT also regulate the expression of an adjacent 5-gene cluster that includes the cabABC operon, brpT, and another VpsT-like transcriptional regulator gene, brpS. The expression of the 14 genes spanning the region increased with elevated intracellular c-di-GMP levels in a BrpT-dependent manner, save for brpS, which was positively regulated by c-di-GMP and repressed by BrpT. BrpS repressed brpA expression and was required for rugose colony development. The mutation of its consensus WFSA c-di-GMP binding motif blocked these activities, suggesting that BrpS function is dependent on binding c-di-GMP. BrpT specifically bound the cabA, brpT, and brpS promoters, and binding sites homologous to the Vibrio cholerae VpsT binding site were identified upstream of brpA and brpT. Transcription was initiated distal to brpA, and a conserved RfaH-recruiting ops element and a potential Rho utilization (rut) terminator site were identified within the 100-bp leader region, suggesting the integration of early termination and operon polarity suppression into the regulation of brp transcription. The GC content and codon usage of the 16-kb brp region was 5.5% lower relative to that of the flanking DNA, suggesting its recent assimilation via horizontal transfer. Thus, architecturally, the brp region can be considered an acquired biofilm and rugosity island that is subject to complex regulation. IMPORTANCE Biofilm and rugose colony formation are developmental programs that underpin the evolution of Vibrio vulnificus as a potent opportunistic human pathogen and successful environmental organism. A better understanding of the regulatory pathways governing theses phenotypes promotes the development and implementation of strategies to mitigate food chain contamination by this pathogen. c-di-GMP signaling is central to both pathways. We show that the molecule orchestrates the expression of 14 genes clustered in a 16-kb segment of the genome that governs biofilm and rugose colony development. This region exhibits the hallmarks of horizontal transfer, suggesting complex regulatory control of a recently assimilated genetic island governing the colonization response of V. vulnificus.


mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Stephen K. Dolan ◽  
Michael Kohlstedt ◽  
Stephen Trigg ◽  
Pedro Vallejo Ramirez ◽  
Clemens F. Kaminski ◽  
...  

ABSTRACT Pseudomonas aeruginosa is an opportunistic human pathogen, particularly noted for causing infections in the lungs of people with cystic fibrosis (CF). Previous studies have shown that the gene expression profile of P. aeruginosa appears to converge toward a common metabolic program as the organism adapts to the CF airway environment. However, we still have only a limited understanding of how these transcriptional changes impact metabolic flux at the systems level. To address this, we analyzed the transcriptome, proteome, and fluxome of P. aeruginosa grown on glycerol or acetate. These carbon sources were chosen because they are the primary breakdown products of an airway surfactant, phosphatidylcholine, which is known to be a major carbon source for P. aeruginosa in CF airways. We show that the fluxes of carbon throughout central metabolism are radically different among carbon sources. For example, the newly recognized “EDEMP cycle” (which incorporates elements of the Entner-Doudoroff [ED] pathway, the Embden-Meyerhof-Parnas [EMP] pathway, and the pentose phosphate [PP] pathway) plays an important role in supplying NADPH during growth on glycerol. In contrast, the EDEMP cycle is attenuated during growth on acetate, and instead, NADPH is primarily supplied by the reaction catalyzed by isocitrate dehydrogenase(s). Perhaps more importantly, our proteomic and transcriptomic analyses revealed a global remodeling of gene expression during growth on the different carbon sources, with unanticipated impacts on aerobic denitrification, electron transport chain architecture, and the redox economy of the cell. Collectively, these data highlight the remarkable metabolic plasticity of P. aeruginosa; that plasticity allows the organism to seamlessly segue between different carbon sources, maximizing the energetic yield from each. IMPORTANCE Pseudomonas aeruginosa is an opportunistic human pathogen that is well known for causing infections in the airways of people with cystic fibrosis. Although it is clear that P. aeruginosa is metabolically well adapted to life in the CF lung, little is currently known about how the organism metabolizes the nutrients available in the airways. In this work, we used a combination of gene expression and isotope tracer (“fluxomic”) analyses to find out exactly where the input carbon goes during growth on two CF-relevant carbon sources, acetate and glycerol (derived from the breakdown of lung surfactant). We found that carbon is routed (“fluxed”) through very different pathways during growth on these substrates and that this is accompanied by an unexpected remodeling of the cell’s electron transfer pathways. Having access to this “blueprint” is important because the metabolism of P. aeruginosa is increasingly being recognized as a target for the development of much-needed antimicrobial agents.


2016 ◽  
Vol 54 (2) ◽  
pp. 134-136 ◽  
Author(s):  
Pablo Ruiz-Sada ◽  
Mikel Escalante ◽  
Eva Lizarralde

AbstractThe role ofSerratia marcescenschanged from a harmless saprophytic microorganism to an important opportunistic human pathogen. It often causes nosocomial device-associated outbreaks and rarely serious invasive community acquired infections. We present a case of a community-acquiredSerratia marcescensbacteremia leading to Respiratory Distress Syndrome in a previously healthy 51-year-old man without identifiable risk factors. Full recovery was achieved with solely medical treatment and observation in ICU during three days. To our knowledge it is an extremely uncommon presentation and just few cases have been previously reported in the literature.


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