scholarly journals Extensive Drug-Resistant Salmonella enterica Isolated From Poultry and Humans: Prevalence and Molecular Determinants Behind the Co-resistance to Ciprofloxacin and Tigecycline

2021 ◽  
Vol 12 ◽  
Author(s):  
Norhan K. Abd El-Aziz ◽  
Yasmine H. Tartor ◽  
Rasha M. A. Gharieb ◽  
Ahmed M. Erfan ◽  
Eman Khalifa ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Efflux Pump ◽  
Point Mutations ◽  
Drug Resistant ◽  
Limited Data ◽  
Genetic Determinants ◽  
Efflux Pump Inhibitor ◽  
Loop Region ◽  
Carbonyl Cyanide ◽  
Molecular Determinants

The emergence of extensive drug-resistant (XDR) Salmonella in livestock animals especially in poultry represents a serious public health and therapeutic challenge. Despite the wealth of information available on Salmonella resistance to various antimicrobials, there have been limited data on the genetic determinants of XDR Salmonella exhibiting co-resistance to ciprofloxacin (CIP) and tigecycline (TIG). This study aimed to determine the prevalence and serotype diversity of XDR Salmonella in poultry flocks and contact workers and to elucidate the genetic determinants involved in the co-resistance to CIP and TIG. Herein, 115 Salmonella enterica isolates of 35 serotypes were identified from sampled poultry (100/1210, 8.26%) and humans (15/375, 4.00%), with the most frequent serotype being Salmonella Typhimurium (26.96%). Twenty-nine (25.22%) Salmonella enterica isolates exhibited XDR patterns; 25 out of them (86.21%) showed CIP/TIG co-resistance. Exposure of CIP- and TIG-resistant isolates to the carbonyl cyanide 3-chlorophenylhydrazone (CCCP) efflux pump inhibitor resulted in an obvious reduction in their minimum inhibitory concentrations (MICs) values and restored the susceptibility to CIP and TIG in 17.24% (5/29) and 92% (23/25) of the isolates, respectively. Molecular analysis revealed that 89.66% of the isolates contained two to six plasmid-mediated quinolone resistance genes with the predominance of qepA gene (89.66%). Mutations in the gyrA gene were detected at codon S83 (34.62%) or D87 (30.77%) or both (34.62%) in 89.66% of XDR Salmonella. The tet(A) and tet(X4) genes were detected in 100% and 3.45% of the XDR isolates, respectively. Twelve TIG-resistant XDR Salmonella had point mutations at codons 120, 121, and 181 in the tet(A) interdomain loop region. All CIP and TIG co-resistant XDR Salmonella overexpressed ramA gene; 17 (68%) out of them harbored 4-bp deletion in the ramR binding region (T-288/A-285). However, four CIP/TIG co-resistant isolates overexpressed the oqxB gene. In conclusion, the emergence of XDR S. enterica exhibiting CIP/TIG co-resistance in poultry and humans with no previous exposure to TIG warrants an urgent need to reduce the unnecessary antimicrobial use in poultry farms in Egypt.

scholarly journals EFFLUX MEDIATED MULTIDRUG RESISTANT PSEUDOMONAS AERUGINOSA ISOLATED FROM DIFFERENT ENVIRONMENTAL SOURCES

2019 ◽  
Vol 17 (1) ◽  
pp. 110-120
Author(s):  
G. C. AGU ◽  
B. T. THOMAS ◽  
O. O. SALAMI ◽  
O. D. POPOOLA
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Environmental Samples ◽  
Efflux Pump ◽  
Opportunistic Pathogen ◽  
Antibiotics Resistance ◽  
Drug Resistant ◽  
Efflux Pump Inhibitor ◽  
Pump System ◽  
Carbonyl Cyanide

Pseudomonas aeruginosa is an important opportunistic pathogen and one of the leading causes of multi-drug resistant nosocomial infections. This study was therefore carried out to determine the resistance nature, and the role of efflux pump in multidrug resistance of Pseudomonas aeruginosa isolated from different environmental sources using the efflux pump inhibitor, Carbonyl Cyanide 3-Chlorophenylhydrazone (CCCP). A total of 220 environmental samples were collected and processed following standard techniques. Susceptibility to antibiotics was performed using disc diffusion methods as described by the Clinical and Laboratory Standards Institute. Activity of the efflux pump system was carried out using the efflux pump inhibitor, CCCP. Results obtained identified 100 (45.5%) Pseudomonas aeruginosa and 72 (32.7%) other strains of Pseudomonas spp. The susceptibility testing revealed that all the identified strains of Pseudomonas aeruginosa that were subjected to susceptibility test were significantly resistant to ampicillin and cefotaxime, But the  resistance profile of isolates to tetracycline, chloramphenicol, ceftriaxone, cefuroxime and perfloxacin were 93%, 72.1%, 79.1%, 58.1% and 51.2% respectively. However, imipenem was the most sensitive (100%), followed by cefepime (65%) and gentamicin (44%). Carbonyl Cyanide 3-Chlorophenylhydrazone decreased the minimum inhibitory concentration (MIC) of the isolates by 2 folds. Results obtained have shown the ubiquitous presence of multi-drug resistant P. aeruginosa from the environmental samples examined. Furthermore, it indicated the role of efflux pump in antibiotics resistance in P. aeruginosa isolates which indicate that P. aeruginosa strains from environmental sources could resist antibiotics by the efflux mechanism.      

Determination of imipenem efflux-mediated resistance in Acinetobacter spp., using an efflux pump inhibitor

2019 ◽  
Author(s):  
Ghazale Amiri ◽  
Maryam Abbasi Shaye ◽  
Masoumeh Bahreini ◽  
Asghar Mafinezhad ◽  
Kiarash Ghazvini ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Efflux Pumps ◽  
Diffusion Method ◽  
Efflux Pump Inhibitor ◽  
Acinetobacter Species ◽  
Fold Reduction ◽  
Carbonyl Cyanide ◽  
Acinetobacter Spp

Background and Objectives: In recent years, reports of Acinetobacter strains resistant to all known antibiotics have caused a great concern in medical communities. Overexpression of efflux pumps is one of the major causes of resistance in bacteria. The aim of this study was to investigate the role of efflux pumps in conferring resistance to imipenem in clinically important Acinetobacter spp; Acinetobacter baumannii and Acinetobacter lwoffii. Materials and Methods: A total number of 46 clinical Acinetobacter isolates, including 33 A. baumannii and 13 A. lwoffii isolates, previously collected from Shahid Kamyab and Ghaem hospitals of Mashhad, Iran were used in this study. Imipenem susceptibility testing was carried out by the disc diffusion method. Imipenem minimum inhibitory concentration (MIC) for resistant Acinetobacter isolates were determined both in the presence and absence of the efflux pumps inhibitor, carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Results: Resistance to imipenem was observed in 38 isolates including 30 A. baumannii and 8 A. lwoffii isolates. Experiments in the presence of CCCP showed a 2 to 16384 fold reduction in imipenem MICs in 14 A. baumannii and 2 A. lwoffii isolates. Conclusion: The results obtained showed high levels of resistance to imipenem and contribution of efflux pumps in conferring resistance in both Acinetobacter species in this study. Moreover, imipenem efflux mediated resistance highlights the importance of this mechanism not only in A. baumannii but also in non-baumannii Acinetobacter Spp. which have been neglected in antibiotic resistance studies.

Copper nanoparticles as an efflux pump inhibitor to tackle drug resistant bacteria

RSC Advances ◽  
2015 ◽  
Vol 5 (17) ◽  
pp. 12899-12909 ◽  
Author(s):  
Lowrence Rene Christena ◽  
Vimalanathan Mangalagowri ◽  
Prabhakaran Pradheeba ◽  
Khan Behlol Ayaz Ahmed ◽  
Bastin Infanta Sandhiya Shalini ◽  
...  
Keyword(s):  
Copper Nanoparticles ◽  
Efflux Pump ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Efflux Pump Inhibitor ◽  
Drug Resistant Bacteria

Casein capped copper nanoparticles at sub inhibitory concentrations function as an efflux pump inhibitor and restores susceptibility to antibiotics in drug resistant bacteria.

Identification of benzochromene derivatives as a highly specific NorA efflux pump inhibitor to mitigate the drug resistant strains of S. aureus

RSC Advances ◽  
2016 ◽  
Vol 6 (36) ◽  
pp. 30258-30267 ◽  
Author(s):  
Asaithampi Ganesan ◽  
Lowrence Rene Christena ◽  
Himesh Makala Venkata Subbarao ◽  
Ulaganathan Venkatasubramanian ◽  
Raman Thiagarajan ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Drug Resistant ◽  
Efflux Pump Inhibitor ◽  
Resistant Strains ◽  
Drug Resistant Strains

Benzochromene (BC) derivatives identified as potent EPI against NorA efflux pump. BC displays 32-fold ciprofloxacin MIC reversal against NorA overexpressing mutant. BC as an adjuvant with antibiotic can curtail MDRS. aureus.

Inhibition of multi-drug resistant Klebsiella pneumoniae: Nanoparticles induced photoinactivation in presence of efflux pump inhibitor

2020 ◽  
Vol 157 ◽  
pp. 165-174
Author(s):  
Shakir Khan ◽  
Shahper N. Khan ◽  
Farheen Akhtar ◽  
Lama Misba ◽  
Ramovatar Meena ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Efflux Pump ◽  
Drug Resistant ◽  
Efflux Pump Inhibitor

scholarly journals Evidence for Active Efflux as the Primary Mechanism of Resistance to Ciprofloxacin in Salmonella enterica Serovar Typhimurium

2000 ◽  
Vol 44 (5) ◽  
pp. 1223-1228 ◽  
Author(s):  
Etienne Giraud ◽  
Axel Cloeckaert ◽  
Dominique Kerboeuf ◽  
Elisabeth Chaslus-Dancla
Keyword(s):  
Outer Membrane ◽  
Salmonella Enterica ◽  
Efflux Pump ◽  
Enzyme Linked Immunosorbent Assay ◽  
Topoisomerase Iv ◽  
Efflux Pump Inhibitor ◽  
Active Efflux ◽  
Fluorimetric Method ◽  
Serovar Typhimurium ◽  
Acrab Efflux Pump

ABSTRACT The occurrence of active efflux and cell wall modifications were studied in Salmonella enterica serovar Typhimurium mutants that were selected with enrofloxacin and whose phenotypes of resistance to fluoroquinolones could not be explained only by mutations in the genes coding for gyrase or topoisomerase IV. Mutant BN18/21 exhibited a decreased susceptibility to ciprofloxacin (MIC = 0.125 μg/ml) but did not have a mutation in the gyrA gene. Mutants BN18/41 and BN18/71 had the same substitution, Gly81Cys in GyrA, but exhibited different levels of resistance to ciprofloxacin (MICs = 2 and 8 μg/ml, respectively). None of the mutants had mutations in the parC gene. Evidence for active efflux was provided by a classical fluorimetric method, which revealed a three- to fourfold decrease in ciprofloxacin accumulation in the three mutants compared to that in the parent strain, which was annuled by addition of the efflux pump inhibitor carbonyl cyanide m-chlorophenylhydrazone. In mutant BN18/71, a second fluorimetric method also showed a 50% reduction in the level of accumulation of ethidium bromide, a known efflux pump substrate. Immunoblotting and enzyme-linked immunosorbent assay experiments with an anti-AcrA antibody revealed that the resistance phenotype was strongly correlated with the expression level of the AcrAB efflux pump and suggested that decreased susceptibility to ciprofloxacin due to active efflux probably related to overproduction of this pump could occur before that due to gyrA mutations. Alterations were also found in the outer membrane protein and lipopolysaccharide profiles of the mutants, and these alterations were possibly responsible for the decrease in the permeability of the outer membrane that was observed in the mutants and that could act synergistically with active efflux to decrease the level of ciprofloxacin accumulation.

Dithiazole thione derivative as competitive NorA efflux pump inhibitor to curtail multi drug resistant clinical isolate of MRSA in a zebrafish infection model

2016 ◽  
Vol 100 (21) ◽  
pp. 9265-9281 ◽  
Author(s):  
Rene Christena Lowrence ◽  
Thiagarajan Raman ◽  
Himesh V. Makala ◽  
Venkatasubramanian Ulaganathan ◽  
Selva Ganesan Subramaniapillai ◽  
...  
Keyword(s):  
Clinical Isolate ◽  
Efflux Pump ◽  
Infection Model ◽  
Drug Resistant ◽  
Efflux Pump Inhibitor ◽  
Zebrafish Infection

scholarly journals Activity of the efflux pump inhibitor SILA 421 against drug-resistant tuberculosis

2013 ◽  
Vol 41 (5) ◽  
pp. 488-489 ◽  
Author(s):  
Sami O. Simons ◽  
Jette E. Kristiansen ◽  
Gyorgy Hajos ◽  
Tridia van der Laan ◽  
József Molnár ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Drug Resistant ◽  
Efflux Pump Inhibitor ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis

scholarly journals Genetic determinants of multi-drug resistance in Acinetobacter baumannii at an academic hospital in Pretoria, South Africa

2019 ◽  
Author(s):  
Noel-David Nogbou ◽  
Dikwata Thabiso Phofa ◽  
Maphoshane Nchabeleng ◽  
Andrew Munyalo Musyoki
Keyword(s):  
South Africa ◽  
Antimicrobial Resistance ◽  
Genetic Relatedness ◽  
Efflux Pump ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Genetic Determinants ◽  
Pump System ◽  
Active Efflux ◽  
Almost All

AbstractAntimicrobial resistance is now globally recognised as the greatest threat to human health. Acinetobacter baumanniis’ (A. baumannii) clinical significance has been driven by its ability to obtain and transmit antimicrobial resistance factors. In South Africa, A. baumannii is a leading cause of healthcare associated infections (HAI). In this study, we investigated the genetic determinants of multi-drug resistant A. baumannii (MDRAB) at a teaching hospital in Pretoria, South Africa.One hundred non repetitive isolates of A. baumannii were collected for the study at Dr George Mukhari Tertiary Laboratory (DGMTL). Antimicrobial susceptibility testing was performed using the VITEK2 system (bioMerieux, France). The prevalence of common resistance associated genes and AdeABC efflux pump system associated genes were investigated using conventional PCR. Genetic relatedness of isolates was then determined using rep-PCR.Seventy (70) of 100 isolates collected were confirmed to be multi-drug resistant and were blaOXA51 positive. Phenotypically, the isolates where resistant to almost all tested antibiotics. However, one isolate showed intermediate susceptibility to tigecycline while all were susceptible to colistin. Oxacillinase encoding gene blaOXA-23 was the most detected at 99% and only 1% was positive for blaOXA-40. The PCR results for metallo-betalactamase (MBL) encoding genes showed that MBL blaVIM was the most frequently detected at 86% and blaSIM-1 at 3% was the least detected. Out of 70 isolates, 56 isolates had the required gene combination for an active efflux pump. The most prevalent clone was clone A at 69% of the isolates. Regarding treatment; colistin and tigecycline are the most effective against strains encountered at DGMTL as all tested carbapenems seem to have lost their effectiveness.The major genotypic determinants for drug resistances are oxacillinases: blaOXA-51 (100%) and blaOXA-23 (99%). The study reports for the first time, blaOXA-40 and blaSIM-1 detection in A. baumannii in South Africa.

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