Enrichment of Persister Cells Through Β-Lactam-Induced Filamentation and Size Separation

2021 ◽  
pp. 63-69
Author(s):  
Etthel Windels ◽  
Bram Van den Bergh ◽  
Jan Michiels
2020 ◽  
Vol 15 (2) ◽  
pp. S27
Author(s):  
F. Haderk ◽  
C. Fernández-Méndez ◽  
K.N. Shah ◽  
W. Wu ◽  
J. Guan ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1870
Author(s):  
Harinash Rao ◽  
Sulin Choo ◽  
Sri Raja Rajeswari Mahalingam ◽  
Diajeng Sekar Adisuri ◽  
Priya Madhavan ◽  
...  

Biofilms play an essential role in chronic and healthcare-associated infections and are more resistant to antimicrobials compared to their planktonic counterparts due to their (1) physiological state, (2) cell density, (3) quorum sensing abilities, (4) presence of extracellular matrix, (5) upregulation of drug efflux pumps, (6) point mutation and overexpression of resistance genes, and (7) presence of persister cells. The genes involved and their implications in antimicrobial resistance are well defined for bacterial biofilms but are understudied in fungal biofilms. Potential therapeutics for biofilm mitigation that have been reported include (1) antimicrobial photodynamic therapy, (2) antimicrobial lock therapy, (3) antimicrobial peptides, (4) electrical methods, and (5) antimicrobial coatings. These approaches exhibit promising characteristics for addressing the impending crisis of antimicrobial resistance (AMR). Recently, advances in the micro- and nanotechnology field have propelled the development of novel biomaterials and approaches to combat biofilms either independently, in combination or as antimicrobial delivery systems. In this review, we will summarize the general principles of clinically important microbial biofilm formation with a focus on fungal biofilms. We will delve into the details of some novel micro- and nanotechnology approaches that have been developed to combat biofilms and the possibility of utilizing them in a clinical setting.


2021 ◽  
Vol 9 (5) ◽  
pp. 943
Author(s):  
Daniel Edelmann ◽  
Florian H. Leinberger ◽  
Nicole E. Schmid ◽  
Markus Oberpaul ◽  
Till F. Schäberle ◽  
...  

Bacterial chromosomes harbor toxin-antitoxin (TA) systems, some of which are implicated in the formation of multidrug-tolerant persister cells. In Escherichia coli, toxin TisB from the tisB/istR-1 TA system depolarizes the inner membrane and causes ATP depletion, which presumably favors persister formation. Transcription of tisB is induced upon DNA damage due to activation of the SOS response by LexA degradation. Transcriptional activation of tisB is counteracted on the post-transcriptional level by structural features of tisB mRNA and RNA antitoxin IstR-1. Deletion of the regulatory RNA elements (mutant Δ1-41 ΔistR) uncouples TisB expression from LexA-dependent SOS induction and causes a ‘high persistence’ (hip) phenotype upon treatment with different antibiotics. Here, we demonstrate by the use of fluorescent reporters that TisB overexpression in mutant Δ1-41 ΔistR inhibits cellular processes, including the expression of SOS genes. The failure in SOS gene expression does not affect the hip phenotype upon treatment with the fluoroquinolone ciprofloxacin, likely because ATP depletion avoids strong DNA damage. By contrast, Δ1-41 ΔistR cells are highly susceptible to the DNA cross-linker mitomycin C, likely because the expression of SOS-dependent repair systems is impeded. Hence, the hip phenotype of the mutant is conditional and strongly depends on the DNA-damaging agent.


Microbiology ◽  
2015 ◽  
Vol 161 (4) ◽  
pp. 786-796 ◽  
Author(s):  
Dorota Kuczyńska-Wiśnik ◽  
Ewelina Matuszewska ◽  
Daria Leszczyńska ◽  
María Moruno Algara ◽  
Karolina Stojowska ◽  
...  

Author(s):  
Julian Clifton ◽  
Paul McDonald ◽  
Andrew Plater ◽  
Frank Oldfield

2021 ◽  
Author(s):  
Rossana de Aguiar Cordeiro ◽  
Bruno Nascimento da Silva ◽  
Ana Luiza Ribeiro de Aguiar ◽  
Livia Maria Galdino Pereira ◽  
Fernando Victor Monteiro Portela ◽  
...  

Abstract Invasive fungal infections (IFIs) are important worldwide health problem, affecting the growing population of immunocompromised patients. Although the majority of IFIs are caused by Candida spp., other fungal species have been increasingly recognized as relevant opportunistic pathogens. Trichosporon spp. are members of skin and gut human microbiota. Since 1980’s, invasive trichosporonosis has been considered a significant cause of fungemia in patients with hematological malignancies. As prolonged antibiotic therapy is an important risk factor for IFIs, the present study investigated if vancomycin enhances growth and virulence of Trichosporon. Vancomycin was tested against T. inkin (n = 6) and T. asahii (n = 6) clinical strains. Planktonic cells were evaluated for their metabolic activity and virulence against Caenorhabditis elegans. Biofilms were evaluated for metabolic activity, biomass production, amphotericin B tolerance, induction of persister cells, and ultrastructure. Vancomycin stimulated planktonic growth of Trichosporon spp., increased tolerance to AMB, and potentiates virulence against C. elegans. Vancomycin stimulated growth (metabolic activity and biomass) of Trichosporon spp. biofilms during all stages of development. The antibiotic increased the number of persister cells inside Trichosporon biofilms. These cells showed higher tolerance to AMB than persister cells from VAN-free biofilms. Microscopic analysis showed that VAN increased production of extracellular matrix and cells in T. inkin and T. asahii biofilms. These results suggest that antibiotic exposure may have a direct impact on the pathophysiology of opportunistic trichosporonosis in patients at risk. Lay abstract This study showed that the vancomycin stimulated Trichosporon growth, induced morphological and physiological changes on their biofilms, and also enhanced their in vivo virulence. Although speculative, the stimulatory effect of vancomycin on fungal cells should be considered in a clinical scenario.


2021 ◽  
Author(s):  
Cassandra L. Schrank ◽  
Ingrid K. Wilt ◽  
Carlos Monteagudo Ortiz ◽  
Brittney A. Haney ◽  
William M. Wuest

This review specifically highlights compounds that have the potential for future development as inhibitors or potentiators of bacterial/persister cells.


2021 ◽  
Author(s):  
Feng Luo ◽  
Li Wang ◽  
Lele Gong ◽  
Wansheng Jia ◽  
Rajamani Krishna ◽  
...  

Abstract Separation of propane from nature gas is of great importance to industry. However, in light of size-based separation, there still lacks effective method to directly separate propane from nature gas, due to the comparable physical properties for these light alkanes (C1-C4) and the middle size of propane. In this work, we found that a new Th-MOF could be an ideal solution for this issue. The Th-MOF takes UiO-66-type structure, but with the pocket sealed by six-fold imide groups; this not only precisely reduces the size of pocket to exactly match propane, but also enhances the host-guest interactions through multiple supramolecular interactions. As a result, highly selective adsorption of propane over methane, ethane, and butane was observed, implying unique middle-size separation. The actual separation was confirmed by breakthrough experiments, and it is found that both relatively smaller molecules (methane and ethane) and relatively bigger molecules (butane) break through the Th-MOF column within 10 min/g, whereas propane with middle size can maintain very long retention time up to 80 min/g, strongly suggesting middle-size separation and its superior application in direct separation of propane from nature gas. The separation mechanism, as unveiled by both theoretical calculation and comparative experiments, is due to the six-fold imide-sealed pockets that could effectively distinguish propane from other light alkanes through both size effect and host-guest interactions.


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