scholarly journals Multidrug Therapy and Evolution of Antibiotic Resistance: When Order Matters

2012 ◽  
Vol 78 (17) ◽  
pp. 6137-6142 ◽  
Author(s):  
Gabriel G. Perron ◽  
Sergey Kryazhimskiy ◽  
Daniel P. Rice ◽  
Angus Buckling
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Pathogenic Bacteria ◽  
Health Workers ◽  
Multiple Drug Resistance ◽  
Sequential Therapy ◽  
Resistant Bacteria ◽  
Multiple Drug ◽  
Multidrug Therapy

ABSTRACTThe evolution of drug resistance among pathogenic bacteria has led public health workers to rely increasingly on multidrug therapy to treat infections. Here, we compare the efficacy of combination therapy (i.e., using two antibiotics simultaneously) and sequential therapy (i.e., switching two antibiotics) in minimizing the evolution of multidrug resistance. Usingin vitroexperiments, we show that the sequential use of two antibiotics againstPseudomonas aeruginosacan slow down the evolution of multiple-drug resistance when the two antibiotics are used in a specific order. A simple population dynamics model reveals that using an antibiotic associated with high costs of resistance first minimizes the chance of multidrug resistance evolution during sequential therapy under limited mutation supply rate. As well as presenting a novel approach to multidrug therapy, this work shows that costs of resistance not only influences the persistence of antibiotic-resistant bacteria but also plays an important role in the emergence of resistance.

scholarly journals Dramatic Activation of Antibiotic Production in Streptomyces coelicolor by Cumulative Drug Resistance Mutations

2008 ◽  
Vol 74 (9) ◽  
pp. 2834-2840 ◽  
Author(s):  
Guojun Wang ◽  
Takeshi Hosaka ◽  
Kozo Ochi
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Antibiotic Production ◽  
Streptomyces Coelicolor ◽  
Strain Improvement ◽  
Multiple Drug ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Order Of Magnitude

ABSTRACT We recently described a new method to activate antibiotic production in bacteria by introducing a mutation conferring resistance to a drug such as streptomycin, rifampin, paromomycin, or gentamicin. This method, however, enhanced antibiotic production by only up to an order of magnitude. Working with Streptomyces coelicolor A3(2), we established a method for the dramatic activation of antibiotic production by the sequential introduction of multiple drug resistance mutations. Septuple and octuple mutants, C7 and C8, thus obtained by screening for resistance to seven or eight drugs, produced huge amounts (1.63 g/liter) of the polyketide antibiotic actinorhodin, 180-fold higher than the level produced by the wild type. This dramatic overproduction was due to the acquisition of mutant ribosomes, with aberrant protein and ppGpp synthesis activity, as demonstrated by in vitro protein synthesis assays and by the abolition of antibiotic overproduction with relA disruption. This new approach, called “ribosome engineering,” requires less time, cost, and labor than other methods and may be widely utilized for bacterial strain improvement.

scholarly journals Mechanisms of bacterial multiresistance to antibiotics

2018 ◽  
Vol 16 (3) ◽  
pp. 4-17 ◽  
Author(s):  
Olga M. Zemlyanko ◽  
Tatyana M. Rogoza ◽  
Galina A. Zhouravleva
Keyword(s):  
Drug Resistance ◽  
Clinical Practice ◽  
Resistance Genes ◽  
Horizontal Transfer ◽  
Pathogenic Bacteria ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Bacterial Strains ◽  
Current Review

Multiple drug resistance (MDR) to widening range of antibiotics emerging in increasing variety of pathogenic bacteria is a serious threat to the health of mankind nowadays. This is partially due to an uncontrolled usage of antibiotics not only in clinical practice, but also in various branches of agriculture. MDR is affected by two mechanisms: (1) accumulation of resistance genes as a result of intensive selection caused by antibiotics, and (2) active horizontal transfer of resistance genes. To unveil the reasons of bacterial multiresistance to antibiotics, it is necessary to understand the mechanisms of antibiotics action as well as the ways how either resistance to certain antibiotics emerge or resistance genes accumulate and transfer among bacterial strains. Current review is devoted to all these problems.

scholarly journals Antibiotic and Disinfectant Susceptibility Patterns of Bacteria Isolated from Farmed Fish in Kirinyaga County, Kenya

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Daniel W. Wanja ◽  
Paul G. Mbuthia ◽  
Robert M. Waruiru ◽  
Lilly C. Bebora ◽  
Helena A. Ngowi ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Drug Resistance ◽  
Sodium Hypochlorite ◽  
Pathogenic Bacteria ◽  
Multiple Drug Resistance ◽  
Diffusion Method ◽  
Resistant Bacteria ◽  
African Catfish ◽  
Ammonium Compound ◽  
Susceptibility Patterns

Fish bacterial pathogens cause diseases which result in a considerable economic impact on the aquaculture industry, necessitating the use of antimicrobials for their control. However, intensive and indiscriminate use of antimicrobials has led to increased occurrence of drug resistance in pathogenic bacteria, as well as normal flora. The aim of the current study was to determine the susceptibility patterns of bacteria isolated from fish, with respect to some commonly used antibiotics and disinfectants. Bacteria were isolated between December 2017 and April 2018 from farmed Nile tilapia, African catfish, goldfish, and koi carp in Kirinyaga County, Kenya. Antibiotic and disinfectant susceptibility patterns of 48 isolates belonging to the genera Aeromonas, Proteus, Klebsiella, Citrobacter, Salmonella, Streptococcus, Pseudomonas, Escherichia, Serratia, and Micrococcus were established using the Kirby–Bauer disc diffusion method and agar well diffusion technique, respectively. The antibiotics evaluated included ampicillin, tetracycline, co-trimoxazole, streptomycin, kanamycin, gentamicin, co-trimoxazole, and chloramphenicol, while the disinfectants tested were quaternary ammonium compound, formalin, hydrogen peroxide, sodium hypochlorite, and iodine. All the bacteria except Micrococcus, Escherichia, and Salmonella species showed multiple drug resistance patterns. Streptococcus showed resistance to six antibiotics, while Proteus, Pseudomonas, and Serratia were resistant to five antibiotics. The multiple antibiotic resistance index ranged from 0.1 to 0.8, with Streptococcus spp. having the highest score value. All the organisms were sensitive to gentamicin, while co-trimoxazole and ampicillin showed the highest resistance at 73% (n = 34) and 62% (n = 31), respectively. Most of the disinfectants showed antibacterial activity with varying magnitudes. The isolates were 100% sensitive to hydrogen peroxide and formalin, but were resistant to sodium hypochlorite at recommended user-dilution. The study has shown that some of the bacterial isolates were resistant to common antibiotics and disinfectants; thus, it is recommended to include an antibiogram whenever making any therapeutic decision. The resistant bacteria may transmit resistance genes to other fish bacteria and also to human bacteria, thus making it difficult to treat the resultant disease(s); thus, there is a possibility that these resistant bacteria may be transmitted to humans who consume or handle the carrier fish. It is, therefore, advisable that fish are cooked properly before consumption, so as to kill bacteria that may be present.

Nanoantibiotics: A Novel Rational Approach to Antibiotic Resistant Infections

2019 ◽  
Vol 20 (9) ◽  
pp. 720-741 ◽  
Author(s):  
Ayse Basak Engin ◽  
Atilla Engin
Keyword(s):  
Drug Resistance ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Multiple Drug Resistance ◽  
Rational Approach ◽  
Resistant Bacteria ◽  
Multiple Drug ◽  
Stimuli Responsive ◽  
Conventional Antibiotics ◽  
Multiple Drugs

Background: The main drawbacks for using conventional antimicrobial agents are the development of multiple drug resistance due to the use of high concentrations of antibiotics for extended periods. This vicious cycle often generates complications of persistent infections, and intolerable antibiotic toxicity. The problem is that while all new discovered antimicrobials are effective and promising, they remain as only short-term solutions to the overall challenge of drug-resistant bacteria. Objective: Recently, nanoantibiotics (nAbts) have been of tremendous interest in overcoming the drug resistance developed by several pathogenic microorganisms against most of the commonly used antibiotics. Compared with free antibiotic at the same concentration, drug delivered via a nanoparticle carrier has a much more prominent inhibitory effect on bacterial growth, and drug toxicity, along with prolonged drug release. Additionally, multiple drugs or antimicrobials can be packaged within the same smart polymer which can be designed with stimuli-responsive linkers. These stimuli-responsive nAbts open up the possibility of creating multipurpose and targeted antimicrobials. Biofilm formation still remains the leading cause of conventional antibiotic treatment failure. In contrast to conventional antibiotics nAbts easily penetrate into the biofilm, and selectively target biofilm matrix constituents through the introduction of bacteria specific ligands. In this context, various nanoparticles can be stabilized and functionalized with conventional antibiotics. These composites have a largely enhanced bactericidal efficiency compared to the free antibiotic. Conclusion: Nanoparticle-based carriers deliver antibiotics with better biofilm penetration and lower toxicity, thus combating bacterial resistance. However, the successful adaptation of nanoformulations to clinical practice involves a detailed assessment of their safety profiles and potential immunotoxicity.

Different Efflux Transporter Affinity and Metabolism of 99mTc-2-methoxyisobutylisonitrile and 99mTc-Tetrofosmin for Multidrug Resistance Monitoring in Cancer Cells

2018 ◽  
Author(s):  
Masato Kobayashi ◽  
Takafumi Tsujiuchi ◽  
Yuya Okui ◽  
Asuka Mizutani ◽  
Kodai Nishi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Human Liver ◽  
High Stability ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Labeled Compounds ◽  
Cancer Resistance ◽  
99Mtc Mibi

Objectives: Little is known about the affinity of 99mTc-labeled 2-methoxyisobutylisonitrile (99mTc-MIBI) and tetrofosmin (99mTc-TF) for multiple drug resistance in cancer cells. Additionally, if 99mTc-labeled compounds are metabolized immediately after injection, imaging with these compounds may not allow monitoring of multiple drug resistance in cancer cells. We examined the affinity of 99mTc-labeled compounds for these transporters and their stability in vivo. Methods: 99mTc-MIBI or 99mTc-TF was incubated in vesicles expressing P-glycoprotein (MDR1), multidrug resistance-associated protein (MRP)1-4, or breast cancer resistance protein with and without verapamil (MDR1 inhibitor) or MK-571 (MRP inhibitor). Time activity curves of 99mTc-labeled compounds were established using SK-N-SH neuroblastoma, SK-MEL-28 melanoma, and PC-3 prostate adenocarcinoma cell lines, and transporter expression of multiple drug resistance was measured in these cells. The stability of 99mTc-labeled compounds was evaluated in mice and human liver S9 fractions. Results: In vesicles, 99mTc-labeled compounds had affinity for MDR1 and MRP1. 99mTc-TF had additional affinity for MRP2 and MRP3. In SK-N-SH cells expressing MDR1 and MRP1, MK-571 produced the highest uptake of both 99mTc-labeled compounds. 99mTc-MIBI uptake with inhibitors was higher than 99mTc-TF uptake with inhibitors. 99mTc-TF was taken up more in SK-MEL-28 cells expressing MRP1 and MRP2 than PC-3 cells expressing MRP1 and MRP3. 99mTc-MIBI was metabolized after a 30-min incubation in SK-N-SH cells, mouse liver, human liver S9 fractions, and plasma. 99mTc-TF had high stability. Conclusion: 99mTc-MIBI is exported via MDR1 and MRP1 (MRP1 > MDR1) at greater levels and more quickly compared to 99mTc-TF, which is exported via MDR1 and MRP1-3 (MRP1 > MDR1; MRP1, 2 > MRP3). Although 99mTc-MIBI is metabolized, clinical imaging for monitoring MDR and shorter examination times may be possible with an earlier scanning time on late phase imaging. 99mTc-TF has high stability and accurately reflects the function of MDR1 and MRP1-3.

scholarly journals Interactions between the gene products of pma1 encoding plasma membrane H(+)-ATPase, and pdr1 controlling multiple drug resistance in Saccharomyces cerevisiae.

1993 ◽  
Vol 40 (4) ◽  
pp. 487-496 ◽  
Author(s):  
S Ułaszewski
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Plasma Membrane ◽  
Atpase Activity ◽  
Multiple Drug Resistance ◽  
Multidrug Resistant ◽  
Multiple Drug ◽  
Gene Products ◽  
In Trans

In Saccharomyces cerevisiae, the pma1 mutations controlling the vanadate resistance of the H(+)-ATPase activity from the plasma membrane, map on chromosome VII in the vicinity of pdr1 mutations controlling multiple drug resistance. However, the pma1-1 mutants exhibit a genotype and a multidrug resistant phenotype quite different from those obtained for pdr1 mutants. Quantitative modifications of cycloheximide and N,N'-(p-xylylidene)-bis-aminoguanidine-2HCl resistance are observed in diploids containing the pma1 and pdr1 genes in trans configuration. Each of the pdr1 mutations interacts with pma1 as shown by a decrease in the ATPase activity in pdr1/pma1 diploids. The in vitro resistance of ATPase activity to vanadate is totally or partially suppressed in pdr1 mutants in haploid double mutants. These results suggest that the expression of PMA1 might be controlled by the PDR1 gene product.

Sign in / Sign up

Export Citation Format

Share Document