scholarly journals Association between Existence of Integrons and Multi-Drug Resistance in Acinetobacter Isolated from Patients in Southern Iran

2011 ◽  
Vol 60 (2) ◽  
pp. 163-168 ◽  
Author(s):  
SARA JAPONI ◽  
AZIZ JAPONI ◽  
SHOREH FARSHAD ◽  
AHYA ABDI ALI ◽  
MARZIEH JAMALIDOUST
Keyword(s):  
Drug Resistance ◽  
Inhibitory Concentration ◽  
Test Method ◽  
Control Measures ◽  
Multi Drug Resistance ◽  
Pcr Assay ◽  
Class 1 ◽  
Antibiotic Susceptibility Patterns ◽  
Susceptibility Patterns

Nosocomial infections caused by multi-drug resistant Acinetobacter pose a serious problem in many countries. This study aimed at determining the antibiotic susceptibility patterns and prevalence of different classes of integrons in isolated Acinetobacter. In addition, the association between production of specific bands in PCR assay and magnitude of multi-drug resistance was investigated. In total, 88 Acinetobacter strains were isolated from patients from October 2008 through September 2009. The Minimal inhibitory concentration (MIC) of 12 antibiotics conventionally used in clinics against the isolates, was determined by E-test method. The existence of integron classes was investigated by PCR assay through the amplification of integrase genes. The most effective antibiotic against Acinetobacter was colistin with 97.7% activity, followed by imipenem (77.3%) and meropenem (72.7%). The presence ofintegron classes 1 and 2 in 47 (53.4%) isolates was confirme, However, no class 3 was detected. The proportion of class 1, compared with class 2, was high (47.7% vs. 3.4%). The association between multi-drug resistance to norfloxacin, ceftazidime, gentamicin, ciprofloxacin, cefepime and amikacin and the presence of integrons was statistically significant. However, the association was not remarkable in many of the isolates which exhibited resistance to the rest of antibiotics. This may imply that in addition to integrons, other resistance determinants such as transposon and plasmid may also contribute to resistance. To reduce the pressure on sensitive isolates, comprehensive control measures should be implemented. Furthermore, wise application of effective antibiotics could help alleviate the situation. Colistin is the most effective antibiotic in vitro against Acinetobacter.

scholarly journals The In Vitro Antibiotic Susceptibility of Malaysian Isolates ofBurkholderia pseudomallei

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Norazah Ahmad ◽  
Rohaidah Hashim ◽  
Azura Mohd Noor
Keyword(s):  
Antibiotic Susceptibility ◽  
Burkholderia Pseudomallei ◽  
Inhibitory Concentration ◽  
Test Method ◽  
Amoxicillin Clavulanic Acid ◽  
Antibiotic Susceptibility Patterns ◽  
Potential Alternative ◽  
Ciprofloxacin Resistance ◽  
Susceptibility Patterns

Acute melioidosis may present as localised or septicaemic infections and can be fatal if left untreated.Burkholderia pseudomalleiresistant to antibiotics used for the treatment of melioidosis had been reported. The aim of this study was to determine the in vitro antibiotic susceptibility patterns ofBurkholderia pseudomalleiisolated in Malaysia to a panel of antibiotics used for the treatment of melioidosis and also to potential alternative antibiotics such as tigecycline, ampicillin/sulbactam, and piperacillin/tazobactam. A total of 170Burkholderia pseudomalleiisolates were subjected to minimum inhibitory concentration determination usingE-test method to eleven antibiotics. All isolates were sensitive to meropenem and piperacillin/tazobactam. For ceftazidime, imipenem, amoxicillin/clavulanic acid, and doxycycline resistance was observed in 1 isolate (0.6%) for each of the antibiotics. Trimethoprim/sulfamethoxazole resistance was observed in 17 (10%) isolates. For other antibiotics, ampicillin/sulbactam, chloramphenicol, tigecycline, and ciprofloxacin resistance were observed in 1 (0.6%), 6 (3.5%), 60 (35.3%) and 98 (57.7%) isolates respectively. One isolate B170/06 exhibited resistance to 4 antibiotics, namely, ciprofloxacin, chloramphenicol, trimethoprim/sulfamethoxazole, and tigecycline. In conclusion, the Malaysian isolates were highly susceptible to the current antibiotics used in the treatment of melioidosis in Malaysia. Multiple resistances to the antibiotics used in the maintenance therapy are the cause for a concern.

scholarly journals Assessment of the Drug Susceptibility of Plasmodium falciparum Clinical Isolates from Africa by Using a Plasmodium Lactate Dehydrogenase Immunodetection Assay and an Inhibitory Maximum Effect Model for Precise Measurement of the 50-Percent Inhibitory Concentration

2006 ◽  
Vol 50 (10) ◽  
pp. 3343-3349 ◽  
Author(s):  
Halima Kaddouri ◽  
Serge Nakache ◽  
Sandrine Houzé ◽  
France Mentré ◽  
Jacques Le Bras
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Active Metabolite ◽  
Inhibitory Concentration ◽  
Drug Susceptibility ◽  
Maximum Effect ◽  
Malaria Parasites ◽  
Effect Model

ABSTRACT The extension of drug resistance among malaria-causing Plasmodium falciparum parasites in Africa necessitates implementation of new combined therapeutic strategies. Drug susceptibility phenotyping requires precise measurements. Until recently, schizont maturation and isotopic in vitro assays were the only methods available, but their use was limited by technical constraints. This explains the revived interest in the development of replacement methods, such as the Plasmodium lactate dehydrogenase (pLDH) immunodetection assay. We evaluated a commercially controlled pLDH enzyme-linked immunosorbent assay (ELISA; the ELISA-Malaria antigen test; DiaMed AG, Cressier s/Morat, Switzerland) to assess drug susceptibility in a standard in vitro assay using fairly basic laboratory equipment to study the in vitro resistance of malaria parasites to major antimalarials. Five Plasmodium falciparum clones and 121 clinical African isolates collected during 2003 and 2004 were studied by the pLDH ELISA and the [8-3H]hypoxanthine isotopic assay as a reference with four antimalarials. Nonlinear regression with a maximum effect model was used to estimate the 50% inhibitory concentration (IC50) and its confidence intervals. The two methods were observed to have similar reproducibilities, but the pLDH ELISA demonstrated a higher sensitivity. The high correlation (r = 0.98) and the high phenotypic agreement (κ = 0.88) between the two methods allowed comparison by determination of the IC50s. Recently collected Plasmodium falciparum African isolates were tested by pLDH ELISA and showed drug resistance or decreased susceptibilities of 62% to chloroquine and 11.5% to the active metabolite of amodiaquine. No decreased susceptibility to lumefantrine or the active metabolite of artemisinin was detected. The availability of this simple and highly sensitive pLDH immunodetection assay will provide an easier method for drug susceptibility testing of malaria parasites.

scholarly journals Tackling resistance: emerging antimalarials and new parasite targets in the era of elimination

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1170 ◽  
Author(s):  
Emily S. Mathews ◽  
Audrey R. Odom John
Keyword(s):  
Drug Resistance ◽  
Malaria Elimination ◽  
Large Scale ◽  
Therapeutic Targets ◽  
Control Measures ◽  
Multi Drug Resistance ◽  
Development Projects ◽  
Combination Therapies ◽  
The Past ◽  
Antimalarial Compounds

Malaria remains a significant contributor to global human mortality, and roughly half the world’s population is at risk for infection with Plasmodium spp. parasites. Aggressive control measures have reduced the global prevalence of malaria significantly over the past decade. However, resistance to available antimalarials continues to spread, including resistance to the widely used artemisinin-based combination therapies. Novel antimalarial compounds and therapeutic targets are greatly needed. This review will briefly discuss several promising current antimalarial development projects, including artefenomel, ferroquine, cipargamin, SJ733, KAF156, MMV048, and tafenoquine. In addition, we describe recent large-scale genetic and resistance screens that have been instrumental in target discovery. Finally, we highlight new antimalarial targets, which include essential transporters and proteases. These emerging antimalarial compounds and therapeutic targets have the potential to overcome multi-drug resistance in ongoing efforts toward malaria elimination.

PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer

2021 ◽  
Author(s):  
xingang wang ◽  
YAN ZHENG ◽  
YU WANG
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Multi Drug Resistance ◽  
Cancer Tissues

Abstract Background and AimsPseudopodium-enriched atypical kinase 1 (PEAK1) has reported to be upregulated in human malignancies and related with poor prognosis. Enhanced PEAK1 expression facilitates tumor cell survival, invasion, metastasis and chemoresistance. However, the role of PEAK1 in breast cancer is not clear. Here, we investigated the PEAK1 expression in breast cancer and analyzed its relation with clinicopathological status and chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated the role of PEAK1 on breast cancer cells in vitro and in vivo. MethodsImmunohistochemistry (IHC) was performed in 112 surgical resected breast cancer tissues. The associations between clinicopathological status, multi-drug resistance and PEAK1 expression were determined. Effect of PEAK1 overexpression or down-expression on proliferation, colony formation, invasion, migration, metastasis and Doxorubicin sensitivity in the MCF-7 cells in vitro and in vivo was detected. ResultsPEAK1 was overexpressed in breast cancer tissues and NAC -resistant breast cancer tissues. High PEAK1 expression was related with tumor size, high tumor grade, T stage, LN metastasis, recurrence, Ki-67 expression, Her-2 expression and multi-drug resistance. Targeting PEAK1 inhibited cell growth, invasion, metastasis and reversed chemoresistance to Doxorubicin in breast cancer cells in vitro and in vivo. ConclusionHigh PEAK1 expression was associated with invasion, metastasis and chemoresistance of breast cancers. Furthermore, targeting PEAK1 could inhibit cell growth and metastasis, and reverse chemoresistance in breast cancer cells, which provides an effective treatment strategies for breast cancer.

scholarly journals In Silico and In Vitro Anti-Helicobacter Pylori Effects of Combinations of Phytochemicals and Antibiotics

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3608 ◽  
Author(s):  
Pedro Fong ◽  
Chon-Hou Hao ◽  
Chi-Cheng Io ◽  
Pou-Io Sin ◽  
Li-Rong Meng
Keyword(s):  
Helicobacter Pylori ◽  
In Silico ◽  
Inhibitory Concentration ◽  
Positive Control ◽  
Shikimate Kinase ◽  
Semialdehyde Dehydrogenase ◽  
Class 1 ◽  
H Pylori ◽  
Potential Inhibitors

Helicobacter pylori infection is a WHO class 1 carcinogenic factor of gastric adenocarcinoma. In the past decades, many studies have demonstrated the increasing trend of antibiotic resistance and pointed out the necessity of new effective treatment. This study was aimed at identifying phytochemicals that can inhibit H. pylori and possibly serve as adjuvant treatments. Here, in silico molecular docking and drug-like properties analyses were performed to identify potential inhibitors of urease, shikimate kinase and aspartate-semialdehyde dehydrogenase. These three enzymes are targets of the treatment of H. pylori. Susceptibility and synergistic testing were performed on the selected phytochemicals and the positive control antibiotic, amoxicillin. The in-silico study revealed that oroxindin, rosmarinic acid and verbascoside are inhibitors of urease, shikimate kinase and aspartate-semialdehyde dehydrogenase, respectively, in which, oroxindin has the highest potency against H. pylori, indicated by a minimum inhibitory concentration (MIC) value of 50 μg/mL. A combination of oroxindin and amoxicillin demonstrated additive effects against H. pylori, as indicated by a fractional inhibitory concentration (FIC) value of 0.75. This study identified phytochemicals that deserve further investigation for the development of adjuvant therapeutic agents to current antibiotics against H. pylori.

scholarly journals Reversal of multi-drug resistance by pSUPER-shRNA-mdr1 in vivo and in vitro

2009 ◽  
Vol 15 (4) ◽  
pp. 431 ◽  
Author(s):  
Guang-Dong Pan ◽  
Jian-Qing Yang ◽  
Lv-Nan Yan ◽  
Guang-Ping Chu ◽  
Qiang Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multi Drug Resistance

scholarly journals LncRNA FEZF1-AS1 Promotes Multi-Drug Resistance of Gastric Cancer Cells via Upregulating ATG5

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhifu Gui ◽  
Zhenguo Zhao ◽  
Qi Sun ◽  
Guoyi Shao ◽  
Jianming Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Multi Drug Resistance ◽  
Gastric Cancer Cells ◽  
Poor Overall Survival

Long non-coding RNAs (lncRNAs) play important roles in human cancers including gastric cancer (GC). Dysregulation of lncRNAs is involved in a variety of pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of FEZF1-AS1 in chemoresistance of GC remain unknown. In this study, we aimed to determine the role of FEZF1-AS1 in chemoresistance of GC. The level of FEZF1-AS1 in GC tissues and GC cell lines was assessed by qRT-PCR. Our results showed that the expression of FEZF1-AS1 was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identified that high level of FEZF1-AS1 is an independent predictor for poor overall survival. Increased FEZF1-AS1 expression promoted gastric cancer cell proliferation in vitro. Additionally, FEZF1-AS1 was upregulated in chemo-resistant GC tissues. The regulatory effect of FEZF1-AS1 on multi-drug resistance (MDR) in GC cells and the underlying mechanism was investigated. It was found that increased FEZF1-AS1 expression promoted chemo-resistance of GC cells. Molecular interactions were determined by RNA immunoprecipitation (RIP) and the results showed that FEZF1-AS1 regulated chemo-resistance of GC cells through modulating autophagy by directly targeting ATG5. The proliferation and autophagy of GC cells promoted by overexpression of LncFEZF1-AS1 was suppressed when ATG5 was knocked down. Moreover, knockdown of FEZF1-AS1 inhibited tumor growth and increased 5-FU sensitivity in GC cells in vivo. Taken together, this study revealed that the FEZF1-AS1/ATG5 axis regulates MDR of GC cells via modulating autophagy.

scholarly journals Multidrug resistance and high prevalence of class 1 integrons in Escherichia coli isolated from waters and vegetables in Nsukka and Enugu, Nigeria

2020 ◽  
Author(s):  
Chinyere B. Chigor ◽  
Ini-Abasi I. Ibangha ◽  
Nkechinyere O. Nweze ◽  
Chizoba A. Ozochi ◽  
Valentino C. Onuora ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Treatment Plant ◽  
Treated Wastewater ◽  
Multi Drug Resistance ◽  
E Coli ◽  
Class 1 Integrons ◽  
High Prevalence ◽  
Class 1

AbstractIn spite of treated wastewater presenting itself as an attractive alternative to scarce quality water in the developing countries, the associated contamination of fresh produce by irrigation waters leading to outbreak of foodborne illnesses is on the rise. Horizontal transfer of integrons play important role in the spread and maintenance of antimicrobial resistance among strains of Escherichia coli. This study assessed the effluents from the University of Nigeria, Nsukka Wastewater Treatment Plant (UNN-WWTP) as well as vegetables irrigated with the effluent, and vegetables sold in selected markets from Nsukka and Enugu cities for the presence of E. coli and determined the prevalence integrons in multidrug-resistant isolates. Isolation of E. coli was done using eosin methylene blue agar and isolates subjected to Gram staining for identification of presumptive colonies. Confirmation of E. coli was achieved by polymerase chain reaction (PCR) technique, targeting beta-glucuronidase (uidA). Resistance to antibiotics was determined using the Bauer-Kirby disk diffusion assay and the Clinical and Laboratory Standard Institute criteria. Integrons were detected by multiplex PCR using primers specific for class 1 and 2 integrons. A total of 178 E. coli isolates were obtained from WWTP effluent (41), and vegetables from greenhouse (46), farms (55) and market (36). Multi-drug resistance was detected in all the isolates, ranging from five-drug resistance in a single isolate to 16-drug resistance patterns in two different isolates. Of the total isolates, class 1 integrons were abundantly detected in 175 (98.3%) and class 2 in 5 (2.8%). All the class 2 integrons were found in isolates that were positive for class 1. The high detection of E. coli in the studied effluent and vegetables pose potential public health hazards heightened by observed multidrug resistance in all the isolates and the high prevalence of class 1 integron. It is concluded that the vegetable samples are significant reservoirs for potentially pathogenic E. coli. Therefore, vegetable irrigation farming with unsafe water should be discontinued, while appropriate improvement strategies to ensure compliance should be facilitated without further delay.

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