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

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.

Gaia Scientia ◽  
2021 ◽  
Vol 15 (2) ◽  
Author(s):  
Raul Vítor Ferreira de Oliveira ◽  
Margareth Borges Coutinho Gallo ◽  
Oscarina Viana de Sousa ◽  
Álef Vasconcelos Ribeiro ◽  
Tatiana Salata Lima ◽  
...  

Brazil is among the world’s largest consumers of pesticides, with glyphosate (GLY) being the most commercialized herbicide in the country. Studies showed microorganisms suffer selective pressure when exposed to pesticides, developing tolerance to pesticides and resistance to antibiotics (ABs), in a phenomenon known as “cross-resistance”. The present work aimed to evaluate the occurrence of glyphosate-tolerance and AB-resistance in bacteria isolated from different agricultural management systems in Ceará State, Brazil. Gram-negative bacteria isolated from agroforestry (S1), conventional farming (S2) and uncultivated (S3) soils were cultured in the presence of 1.6% acid glyphosate. Overall, 58 strains were isolated. Soils S1 and S2 presented several multidrug resistant (MDR) strains, the majority resistant to ampicilin. Although there was a small percentage of strains resistant to ertapenem (33%, soil S1), the fact they were found is concerning, as Carbapenem antibiotics are used to treat clinical cases of MDR bacteria, which are not common outside hospital settings. Stenotrophomonas maltophilia (soil S2), resistant to six of the eight ABs tested, was identified by MALDI-TOF mass spectrometry, and was found as one of the most common opportunistic bacteria in ICUs of Ceará hospitals.


Author(s):  
Alicia M. Churchill-Angus ◽  
Svetlana E. Sedelnikova ◽  
Thomas H. B. Schofield ◽  
Patrick J. Baker

Tripartite α-pore-forming toxins are constructed of three proteins (A, B and C) and are found in many bacterial pathogens. While structures of the B and C components from Gram-negative bacteria have been described, the structure of the A component of a Gram-negative α-pore-forming toxin has so far proved elusive. SmhA, the A component from the opportunistic human pathogen Serratia marcescens, has been cloned, overexpressed and purified. Crystals were grown of selenomethionine-derivatized protein and anomalous data were collected. Phases were calculated and an initial electron-density map was produced.


2021 ◽  
Vol 22 (4) ◽  
pp. 1717
Author(s):  
Małgorzata Mizielińska ◽  
Paweł Nawrotek ◽  
Xymena Stachurska ◽  
Magdalena Ordon ◽  
Artur Bartkowiak

The purpose of the study was to obtain an external coating based on nanoparticles of ZnO, carvacrol, and geraniol that could be active against viruses such as SARS-Co-V2. Additionally, the synergistic effect of the chosen substances in coatings was analyzed. The goal of the study was to measure the possible antibacterial activity of the coatings obtained. Testing antiviral activity with human pathogen viruses, such as SARS-Co-V2, requires immense safety measures. Bacteriophages such as phi 6 phage represent good surrogates for the study of airborne viruses. The results of the study indicated that the ZC1 and ZG1 coatings containing an increased amount of geraniol or carvacrol and a very small amount of nanoZnO were found to be active against Gram-positive and Gram-negative bacteria. It is also important that a synergistic effect between these active substances was noted. This explains why polyethylene (PE) films covered with the ZC1 or ZG1 coatings (as internal coatings) were found to be the best packaging materials to extend the quality and freshness of food products. The same coatings may be used as the external coatings with antiviral properties. The ZC1 and ZG1 coatings showed moderate activity against the phi 6 phage that has been selected as a surrogate for viruses such as coronaviruses. It can be assumed that coatings ZG1 and ZC1 will also be active against SARS-CoV-2 that is transmitted via respiratory droplets.


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.


2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ryan K. Shields

ABSTRACT Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.


2019 ◽  
Vol 113 (2) ◽  
pp. 492-503 ◽  
Author(s):  
Karina Calvopiña ◽  
Punyawee Dulyayangkul ◽  
Kate J. Heesom ◽  
Matthew B. Avison

2009 ◽  
Vol 36 (3) ◽  
pp. 512-519 ◽  
Author(s):  
Saskia Nijssen ◽  
Ad Fluit ◽  
David van de Vijver ◽  
Janetta Top ◽  
Rob Willems ◽  
...  

2002 ◽  
Vol 1562 (1-2) ◽  
pp. 6-31 ◽  
Author(s):  
Ming-Ren Yen ◽  
Christopher R. Peabody ◽  
Salar M. Partovi ◽  
Yufeng Zhai ◽  
Yi-Hsiung Tseng ◽  
...  

2010 ◽  
Vol 54 (6) ◽  
pp. 2583-2589 ◽  
Author(s):  
Yi-Wei Huang ◽  
Cheng-Wen Lin ◽  
Rouh-Mei Hu ◽  
Yu-Tzu Lin ◽  
Tung-Ching Chung ◽  
...  

ABSTRACT AmpG is an inner membrane permease which transports products of murein sacculus degradation from the periplasm into the cytosol in Gram-negative bacteria. This process is linked to induction of the chromosomal ampC beta-lactamase gene in some members of the Enterobacteriaceae and in Pseudomonas aeruginosa. In this study, the ampG homologue of Stenotrophomonas maltophilia KJ was analyzed. The ampG homologue and its upstream ampN gene form an operon and are cotranscribed under the control of the promoter P ampN. Expression from P ampN was found to be independent of β-lactam exposure and ampN and ampG products. A ΔampN allele exerted a polar effect on the expression of ampG and resulted in a phenotype of null β-lactamase inducibility. Complementation assays elucidated that an intact ampN-ampG operon is essential for β-lactamase induction. Consistent with ampG of Escherichia coli, the ampN-ampG operon of S. maltophilia did not exhibit a gene dosage effect on β-lactamase expression. The AmpG permease of E. coli could complement the β-lactamase inducibility of ampN or ampG mutants of S. maltophilia, indicating that both species have the same precursor of activator ligand(s) for β-lactamase induction.


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