scholarly journals Susceptibility of Pseudomonas aeruginosa Dispersed Cells to Antimicrobial Agents Is Dependent on the Dispersion Cue and Class of the Antimicrobial Agent Used

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Jacob R. Chambers ◽  
Kathryn E. Cherny ◽  
Karin Sauer

ABSTRACT The biofilm life cycle is characterized by the transition of planktonic cells exhibiting high susceptibly to antimicrobial agents to a biofilm mode of growth characterized by high tolerance to antimicrobials, followed by dispersion of cells from the biofilm back into the environment. Dispersed cells, however, are not identical to planktonic cells but have been characterized as having a unique transitionary phenotype relative to biofilm and planktonic cells, with dispersed cells attaching in a manner similar to exponential-phase cells, but demonstrating gene expression patterns that are distinct from both exponential and stationary-phase planktonic cells. This raised the question whether dispersed cells are as susceptible as planktonic cells and whether the dispersion inducer or the antibiotic class affects the drug susceptibility of dispersed cells. Dispersed cells obtained in response to dispersion cues glutamate and nitric oxide (NO) were thus exposed to tobramycin and colistin. Although NO-induced dispersed cells were as susceptible to colistin and tobramycin as exponential-phase planktonic cells, glutamate-induced dispersed cells were susceptible to tobramycin but resistant to colistin. The difference in colistin susceptibility was independent of cellular c-di-GMP levels, with modulation of c-di-GMP failing to induce dispersion. Instead, drug susceptibility was inversely correlated with LPS modification system and the biofilm-specific transcriptional regulator BrlR. The susceptibility phenotype of glutamate-induced dispersed cells to colistin was found to be reversible, with dispersed cells being rendered as susceptible to colistin within 2 h postdispersion, though additional time was required for dispersed cells to display expression of genes indicative of exponential growth.

2001 ◽  
Vol 45 (6) ◽  
pp. 1761-1770 ◽  
Author(s):  
Teresa R. De Kievit ◽  
Michael D. Parkins ◽  
Richard J. Gillis ◽  
Ramakrishnan Srikumar ◽  
Howard Ceri ◽  
...  

ABSTRACT Pseudomonas aeruginosa biofilms are intrinsically resistant to antimicrobial chemotherapies. At present, very little is known about the physiological changes that occur during the transition from the planktonic to biofilm mode of growth. The resistance ofP. aeruginosa biofilms to numerous antimicrobial agents that are substrates subject to active efflux from planktonic cells suggests that efflux pumps may substantially contribute to the innate resistance of biofilms. In this study, we investigated the expression of genes associated with two multidrug resistance (MDR) efflux pumps, MexAB-OprM and MexCD-OprJ, throughout the course of biofilm development. Using fusions to gfp, we were able to analyze spatial and temporal expression of mexA andmexC in the developing biofilm. Remarkably, expression ofmexAB-oprM and mexCD-oprJ was not upregulated but rather decreased over time in the developing biofilm. Northern blot analysis confirmed that these pumps were not hyperexpressed in the biofilm. Furthermore, spatial differences in mexAB-oprM andmexCD-oprJ expression were observed, with maximal activity occurring at the biofilm substratum. Using a series of MDR mutants, we assessed the contribution of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY efflux pumps to P. aeruginosa biofilm resistance. These analyses led to the surprising discovery that the four characterized efflux pumps do not play a role in the antibiotic-resistant phenotype of P. aeruginosa biofilms.


2021 ◽  
Vol 937 (2) ◽  
pp. 022125
Author(s):  
N Vasilchenko ◽  
K Mekhantseva ◽  
A Gorovtsov ◽  
V Chistyakov ◽  
L Alekseenko ◽  
...  

Abstract The article presents data on the effect of phytopathogenic fungi of the genus Fusarium on the expression of genes responsible for the synthesis of various enzymes and other protein molecules involved in the induced immunity of Triticum aestivum plants (Pathogen Resistance protein, PR - proteins). The effect of suspensions containing conidia of phytopathogenic fungi in various concentrations (104,106,108 conidia per 1 ml per 100 grams of seeds) was evaluated under the conditions of a model experiment. The data on the effect of Fusarium fungi on the morphometric parameters of winter wheat are also presented. During the work, it was found that the treatment with a conidial suspension has the greatest effect on morphometric parameters, and over time the difference with the control becomes the most noticeable; and that in the presence of fungi the expression of pathogenesis-associated protein PR-1, chitinase PR-3 and inhibitor of proteinases (PR-6) is the most active.


Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1456
Author(s):  
Xin Jin ◽  
Can Baysal ◽  
Margit Drapal ◽  
Yanmin Sheng ◽  
Xin Huang ◽  
...  

Light is an essential regulator of many developmental processes in higher plants. We investigated the effect of 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 1/2 genes (OsHDR1/2) and isopentenyl diphosphate isomerase 1/2 genes (OsIPPI1/2) on the biosynthesis of chlorophylls, carotenoids, and phytosterols in 14-day-old etiolated rice (Oyza sativa L.) leaves during de-etiolation. However, little is known about the effect of isoprenoid biosynthesis genes on the corresponding metabolites during the de-etiolation of etiolated rice leaves. The results showed that the levels of α-tocopherol were significantly increased in de-etiolated rice leaves. Similar to 1-deoxy-D-xylulose-5-phosphate synthase 3 gene (OsDXS3), both OsDXS1 and OsDXS2 genes encode functional 1-deoxy-D-xylulose-5-phosphate synthase (DXS) activities. Their expression patterns and the synthesis of chlorophyll, carotenoid, and tocopherol metabolites suggested that OsDXS1 is responsible for the biosynthesis of plastidial isoprenoids in de-etiolated rice leaves. The expression analysis of isoprenoid biosynthesis genes revealed that the coordinated expression of the MEP (2-C-methyl-D-erythritol 4-phosphate) pathway, chlorophyll, carotenoid, and tocopherol pathway genes mirrored the changes in the levels of the corresponding metabolites during de-etiolation. The underpinning mechanistic basis of coordinated light-upregulated gene expression was elucidated during the de-etiolation process, specifically the role of light-responsive cis-regulatory motifs in the promoter region of these genes. In silico promoter analysis showed that the light-responsive cis-regulatory elements presented in all the promoter regions of each light-upregulated gene, providing an important link between observed phenotype during de-etiolation and the molecular machinery controlling expression of these genes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebecca Rani Das Gupta ◽  
Louis Scheurer ◽  
Pawel Pelczar ◽  
Hendrik Wildner ◽  
Hanns Ulrich Zeilhofer

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (vGluT2+) and inhibitory GABA and/or glycinergic (vGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are not only set apart, as expected, by the expression of genes related to the production, release or re-uptake of their principal neurotransmitters and by genes encoding for transcription factors, but also by a differential engagement of neuromodulator, especially neuropeptide, signaling pathways. Subsequent multiplex in situ hybridization revealed eleven neuropeptide genes that are strongly enriched in excitatory dorsal horn neurons and display largely non-overlapping expression patterns closely adhering to the laminar and presumably also functional organization of the spinal cord grey matter.


Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 2090-2093 ◽  
Author(s):  
Dirk Kienle ◽  
Axel Benner ◽  
Alexander Kröber ◽  
Dirk Winkler ◽  
Daniel Mertens ◽  
...  

The mutation status and usage of specific VH genes such as V3-21 and V1-69 are potentially independent pathogenic and prognostic factors in chronic lymphocytic leukemia (CLL). To investigate the role of antigenic stimulation, we analyzed the expression of genes involved in B-cell receptor (BCR) signaling/activation, cell cycle, and apoptosis control in CLL using these specific VH genes compared to VH mutated (VH-MUT) and VH unmutated (VH-UM) CLL not using these VH genes. V3-21 cases showed characteristic expression differences compared to VH-MUT (up: ZAP70 [or ZAP-70]; down: CCND2, P27) and VH-UM (down: PI3K, CCND2, P27, CDK4, BAX) involving several BCR-related genes. Similarly, there was a marked difference between VH unmutated cases using the V1-69 gene and VH-UM (up: FOS; down: BLNK, SYK, CDK4, TP53). Therefore, usage of specific VH genes appears to have a strong influence on the gene expression pattern pointing to antigen recognition and ongoing BCR stimulation as a pathogenic factor in these CLL subgroups.


2012 ◽  
Vol 75 (4) ◽  
pp. 637-642 ◽  
Author(s):  
RONALD GAELEKOLWE SAMAXA ◽  
MAITSHWARELO IGNATIUS MATSHEKA ◽  
SUNUNGUKO WATA MPOLOKA ◽  
BERHANU ABEGAZ GASHE

The objective of the study was to provide baseline data on the prevalence and antimicrobial susceptibility of Salmonella in different types of raw meat sausages directly accessible to the consumers in Gaborone, Botswana. A total of 300 raw sausages comprising 79 beef, 78 pork, 72 chicken, and 71 mutton samples were concurrently analyzed for the presence of Salmonella using a conventional culture method and a validated PCR method. The PCR assay results were in full concordance with those of the conventional culture method for the detection of Salmonella. Sixty-five (21.7%) of 300 samples were positive for Salmonella by both the conventional culture method and PCR assay. Even though more chicken samples contained Salmonella than did any other sausage type, the difference in the presence of Salmonella among the four sausages types was not significant. Eleven serotypes were identified, and Salmonella enterica subsp. salamae II was most prevalent in all the sausage types. Beef sausages generally had higher mesophilic bacterial counts than did the other three sausage types. However, higher microbial counts were not reflective of the presence of salmonellae. Susceptibility of the Salmonella enterica serotypes to 20 antimicrobial agents was determined, and Salmonella Muenchen was resistant to the widest array of agents and was mostly isolated from chicken sausages. Regardless of the meat of origin, all 65 Salmonella isolates were resistant to at least four antimicrobial agents: amikacin, gentamicin, cefuroxime, and tombramycin. This resistance profile group was the most common in all four sausage types, comprising 90% of all Salmonella isolates from beef, 71% from pork, 63% from mutton, and 35% from chicken. These results suggest that raw sausages pose a risk of transmitting multidrug-resistant Salmonella isolates to consumers.


Author(s):  
Denis Bienroth ◽  
Hieu T. Nim ◽  
Dimitar Garkov ◽  
Karsten Klein ◽  
Sabrina Jaeger-Honz ◽  
...  

AbstractSpatially resolved transcriptomics is an emerging class of high-throughput technologies that enable biologists to systematically investigate the expression of genes along with spatial information. Upon data acquisition, one major hurdle is the subsequent interpretation and visualization of the datasets acquired. To address this challenge, VR-Cardiomicsis presented, which is a novel data visualization system with interactive functionalities designed to help biologists interpret spatially resolved transcriptomic datasets. By implementing the system in two separate immersive environments, fish tank virtual reality (FTVR) and head-mounted display virtual reality (HMD-VR), biologists can interact with the data in novel ways not previously possible, such as visually exploring the gene expression patterns of an organ, and comparing genes based on their 3D expression profiles. Further, a biologist-driven use-case is presented, in which immersive environments facilitate biologists to explore and compare the heart expression profiles of different genes.


2008 ◽  
Vol 52 (3) ◽  
pp. 1127-1132 ◽  
Author(s):  
Priya Uppuluri ◽  
Jeniel Nett ◽  
Joseph Heitman ◽  
David Andes

ABSTRACT Calcineurin is a Ca2+-calmodulin-activated serine/threonine-specific protein phosphatase that governs multiple aspects of fungal physiology, including cation homeostasis, morphogenesis, antifungal drug susceptibility, and virulence. Growth of Candida albicans planktonic cells is sensitive to the calcineurin inhibitors FK506 and cyclosporine A (CsA) in combination with the azole antifungal fluconazole. This drug synergism is attributable to two effects: first, calcineurin inhibitors render fluconazole fungicidal rather than simply fungistatic, and second, membrane perturbation by azole inhibition of ergosterol biosynthesis increases intracellular calcineurin inhibitor concentrations. C. albicans cells in biofilms are up to 1,000-fold more resistant to fluconazole than planktonic cells. In both in vitro experiments and in an in vivo rat catheter model, C. albicans cells in biofilms were resistant to individually delivered fluconazole or calcineurin inhibitors but exquisitely sensitive to the combination of FK506-fluconazole or CsA-fluconazole. C. albicans strains lacking FKBP12 or expressing a dominant FK506-resistant calcineurin mutant subunit (Cnb1-1) formed biofilms that were resistant to FK506-fluconazole but susceptible to CsA-fluconazole, demonstrating that drug synergism is mediated via direct calcineurin inhibition. These findings reveal that calcineurin contributes to fluconazole resistance of biofilms and provide evidence that synergistic drug combinations may prove efficacious as novel therapeutic interventions to treat or prevent biofilms.


2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096229
Author(s):  
Jiachang Liu ◽  
Ruikai Wang ◽  
Ming Fang

Objectives To investigate the clinical and drug resistance characteristics of Providencia stuartii infections in the Huainan region of Anhui and provide a reference for the clinical selection of antimicrobial agents. Methods This single-center retrospective analysis included 76 patients with P. stuartii infection in Huainan during the period from October 2018 to March 2020. The hospital department in which the patients were treated and the drug susceptibility characteristics of the P. stuartii isolates were recorded. Results Among the 76 patients, the lung was the most common site of infection, and intensive care unit was the main hospital department. Extended spectrum beta-lactamase screening revealed expression by all 76 isolates of P. stuartii. Of the 76 isolates, 92.1% exhibited multiple drug resistance or extensive drug resistance. P. stuartii isolates were sensitive to cefepime and imipenem, but not to other beta-lactam antibiotics. Twenty isolates were resistant to all 21 types of antibiotics. Of the 20 patients infected with extensively drug-resistant isolates, nine (45%) died. Conclusions Drug resistance is increasing in P. stuartii. The antimicrobial agent imipenem may be effective for treatment of P. stuartii infections. Fluoroquinolones, aminoglycosides, and fourth-generation cephalosporins are suitable options for antibiotic therapy.


2019 ◽  
Vol 117 (38) ◽  
pp. 23317-23322 ◽  
Author(s):  
Joaquín Sanz ◽  
Paul L. Maurizio ◽  
Noah Snyder-Mackler ◽  
Noah D. Simons ◽  
Tawni Voyles ◽  
...  

Social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB–dependent proinflammatory pathways and lower expression of genes involved in the antiviral response and type I IFN signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB– and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are linked not only to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Taken together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history—in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.


Sign in / Sign up

Export Citation Format

Share Document