Lactobacillus rhamnosus cell-free extract targets virulence and antifungal drug resistance in Candida albicans

2020 ◽  
Vol 66 (12) ◽  
pp. 733-747
Author(s):  
Yvonne Dube ◽  
Amber Khan ◽  
Musa Marimani ◽  
Aijaz Ahmad
Keyword(s):  
Drug Resistance ◽  
Lactobacillus Rhamnosus ◽  
Chemical Characterization ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Gas Chromatography Mass Spectrometry ◽  
Drug Efflux ◽  
Antifungal Drug Resistance ◽  
Virulence Traits ◽  
Drug Efflux Pumps

Candidiasis caused by multidrug-resistant Candida species continues to be difficult to eradicate. The use of live probiotic bacteria has gained a lot of interest in the treatment of candidiasis; however, whole-cell probiotic use can often be associated with a high risk of sepsis. Strategies manipulating cell-free methods using probiotic strains could lead to the development of novel antifungal solutions. Therefore, we evaluated the effect of three probiotic cell-free extracts (CFEs) on the growth, virulence traits, and drug efflux pumps in C. albicans. On the basis of its minimum inhibitory concentration, Lactobacillus rhamnosus was selected and assessed against various virulence traits and drug resistance mechanisms. The results showed that L. rhamnosus CFE significantly inhibited hyphae formation and reduced secretion of proteinases and phospholipases. Moreover, L. rhamnosus inhibited the drug efflux proteins in resistant C. albicans strains thus reversing drug resistance. Gene expression data confirmed downregulation of genes associated with microbial virulence and drug resistance following treatment of C. albicans with L. rhamnosus CFE. Through gas chromatography – mass spectrometry chemical characterization, high contents of oleic acid (24.82%) and myristic acid (13.11%) were observed in this CFE. Collectively, our findings indicate that L. rhamnosus may potentially be used for therapeutic purposes to inhibit C. albicans infections.

scholarly journals Pseudomonas aeruginosa May Accumulate Drug Resistance Mechanisms without Losing Its Ability To Cause Bloodstream Infections

2007 ◽  
Vol 51 (10) ◽  
pp. 3531-3536 ◽  
Author(s):  
Didier Hocquet ◽  
Philippe Berthelot ◽  
Micheline Roussel-Delvallez ◽  
Roger Favre ◽  
Katy Jeannot ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Resistance ◽  
Gel Electrophoresis ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Pulsed Field Gel Electrophoresis ◽  
Drug Efflux ◽  
Pulsed Field

ABSTRACT In this study, we systematically investigated the resistance mechanisms to β-lactams, aminoglycosides, and fluoroquinolones of 120 bacteremic strains of Pseudomonas aeruginosa. Pulsed-field gel electrophoresis genotyping showed that 97 of these strains were represented by a single isolate, 10 by 2 and 1 by 3 clonally related isolates, respectively. Seventy-five percent (90 out of 120) of the bacteremic P. aeruginosa strains displayed a significant resistance to one or more of the tested antimicrobials (up to 11 for 1 strain). These strains were found to harbor a great diversity of resistance mechanisms (up to 7 in 1 strain), leading to various levels of drug resistance. Interestingly, 11 and 36% of the isolates appeared to overproduce the MexAB-OprM and MexXY-OprM efflux systems, respectively. Altogether, our results show that P. aeruginosa may accumulate intrinsic (overproduction of cephalosporinase AmpC, increased drug efflux, fluoroquinolone target mutations, and deficient production of porin OprD) and exogenous (production of secondary β-lactamases and aminoglycoside-modifying enzymes) resistance mechanisms without losing its ability to generate severe bloodstream infections. Consequently, clinicians should be aware that multidrug-resistant P. aeruginosa may remain fully pathogenic.

scholarly journals A Broad-Specificity Multidrug Efflux Pump Requiring a Pair of Homologous SMR-Type Proteins

2000 ◽  
Vol 182 (8) ◽  
pp. 2311-2313 ◽  
Author(s):  
Donald L. Jack ◽  
Michael L. Storms ◽  
Jason H. Tchieu ◽  
Ian T. Paulsen ◽  
Milton H. Saier
Keyword(s):  
Escherichia Coli ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Drug Efflux ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Resistant Phenotype ◽  
Small Multidrug Resistance ◽  
Drug Efflux Pumps ◽  
Broad Specificity

ABSTRACT The Bacillus subtilis genome encodes seven homologues of the small multidrug resistance (SMR) family of drug efflux pumps. Six of these homologues are paired in three distinct operons, and coexpression in Escherichia coli of one such operon,ykkCD, but not expression of either ykkC orykkD alone, gives rise to a broad specificity, multidrug-resistant phenotype including resistance to cationic, anionic, and neutral drugs.

scholarly journals Comparative analytical evaluation of four centralized platforms for the detection of M. tuberculosis complex and resistance to rifampicin and isoniazid

2020 ◽  
Author(s):  
Margaretha de Vos ◽  
Lesley Scott ◽  
Anura David ◽  
Andre Trollip ◽  
Harald Hoffmann ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Limit Of Detection ◽  
Clinical Performance ◽  
Analytical Data ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Analytical Sensitivity ◽  
Isoniazid Resistance ◽  
Mdr Tb ◽  
Resistance Detection

Failure to rapidly identify drug-resistant tuberculosis (TB) increases the risk of patient mismanagement, the amplification of drug resistance and ongoing transmission. We generated comparative analytical data for four automated assays for detection of TB and multidrug-resistant (MDR) TB: Abbott RealTime MTB and MTB RIF/INH (Abbott), Hain Lifescience FluoroType® MTBDR (Hain), BD MAX™ MDR-TB (BD) and Roche cobas® MTB and MTB-RIF/INH (Roche). We included Xpert MTB/RIF (Xpert) and GenoType MTBDRplus as comparators for TB and drug resistance detection, respectively. We assessed analytical sensitivity for the detection of Mycobacterium tuberculosis complex using inactivated strains (M. tuberculosis H37Rv and M. bovis) spiked into TB-negative sputa and computed the 95% limit of detection (LOD95). We assessed the accuracy for rifampicin and isoniazid resistance detection using well characterized M. tuberculosis strains with high-confidence mutations accounting for >85% of first-line resistance mechanisms globally. For H37Rv and M. bovis, respectively, we measured LOD95 values of 3,781 and 2,926 (Xpert); 322 and 2,182 (Abbott); 826 and 4,301 (BD); 10,398 and 23,139 (Hain); 2,416 and 2,136 (Roche) genomes/mL. Assays targeting multi-copy genes or targets (Abbott, BD and Roche) showed increased analytical sensitivity compared to Xpert. Quantification of the panel by quantitative real-time PCR prevents the determination of absolute values and results reported here can only be interpreted for comparison purposes. All assays showed accuracy comparable to Genotype MTBDRplus for the detection of rifampicin and isoniazid resistance. The data from this analytical study suggest that the assays may have similar clinical performance to WHO-recommended molecular TB and MDR-TB assays.

scholarly journals The Action of Efflux Pump Genes in Conferring Drug Resistance to Klebsiella Species and Their Inhibition

2021 ◽  
Author(s):  
Priyanka Ashwath ◽  
Akhila Dharnappa Sannejal
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Klebsiella Species ◽  
Gram Negative ◽  
Multidrug Efflux Pumps

AbstractNosocomial infections caused by Klebsiella species are characterized by high rates of morbidity and mortality. The emergence of the multidrug-resistant (MDR) and extensive drug-resistant (XDR) Gram-negative bacteria reduces the antibiotic efficacy in the treatment of infections caused by the microorganisms. Management of these infections is often difficult, due to the high frequency of strains resistant to multiple antimicrobial agents. Multidrug efflux pumps play a major role as a mechanism of antimicrobial resistance in Gram-negative pathogens. Efflux systems are significant in conferring intrinsic and acquired resistance to the bacteria. The emergence of increasing drug resistance among Klebsiella pneumoniae nosocomial isolates has limited the therapeutic options for treatment of these infections and hence there is a constant quest for an alternative. In this review, we discuss various resistance mechanisms, focusing on efflux pumps and related genes in conferring resistance to Klebsiella. The role of various efflux pump inhibitors (EPIs) in restoring the antibacterial activity has also been discussed. In specific, antisense oligonucleotides as alternative therapeutics in combatting efflux-mediated resistance in Klebsiella species have focused upon.

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