scholarly journals Ubiquitous Conjugative Mega-Plasmids of Acinetobacter Species and Their Role in Horizontal Transfer of Multi-Drug Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Sofia Mindlin ◽  
Olga Maslova ◽  
Alexey Beletsky ◽  
Varvara Nurmukanova ◽  
Zhiyong Zong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Antibiotic Resistance Genes ◽  
Multi Drug Resistance ◽  
Clear Correlation ◽  
Multiple Drug ◽  
Special Role ◽  
Acinetobacter Species ◽  
Group Iii

Conjugative mega-plasmids play a special role in adaptation since they carry a huge number of accessory genes, often allowing the host to develop in new niches. In addition, due to conjugation they are able to effectively spread themselves and participate in the transfer of small mobilizable plasmids. In this work, we present a detailed characterization of a recently discovered family of multiple-drug resistance mega-plasmids of Acinetobacter species, termed group III-4a. We describe the structure of the plasmid backbone region, identify the rep gene and the origin of plasmid replication, and show that plasmids from this group are able not only to move between different Acinetobacter species but also to efficiently mobilize small plasmids containing different mob genes. Furthermore, we show that the population of natural Acinetobacter strains contains a significant number of mega-plasmids and reveal a clear correlation between the living conditions of Acinetobacter strains and the structure of their mega-plasmids. In particular, comparison of the plasmids from environmental and clinical strains shows that the genes for resistance to heavy metals were eliminated in the latter, with the simultaneous accumulation of antibiotic resistance genes by incorporation of transposons and integrons carrying these genes. The results demonstrate that this group of mega-plasmids plays a key role in the dissemination of multi-drug resistance among Acinetobacter species.

scholarly journals S-Adenosylmethionine Increases the Sensitivity of Human Colorectal Cancer Cells to 5-Fluorouracil by Inhibiting P-Glycoprotein Expression and NF-κB Activation

2021 ◽  
Vol 22 (17) ◽  
pp. 9286
Author(s):  
Laura Mosca ◽  
Martina Pagano ◽  
Luigi Borzacchiello ◽  
Luigi Mele ◽  
Annapina Russo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Defense Mechanism ◽  
Multiple Drug Resistance ◽  
Nutritional Supplement ◽  
Multi Drug Resistance ◽  
Multiple Drug ◽  
Cell Defense ◽  
P Glycoprotein

Colorectal cancer (CRC) is the second deadliest cancer worldwide despite significant advances in both diagnosis and therapy. The high incidence of CRC and its poor prognosis, partially attributed to multi-drug resistance and antiapoptotic activity of cancer cells, arouse strong interest in the identification and development of new treatments. S-Adenosylmethionine (AdoMet), a natural compound and a nutritional supplement, is well known for its antiproliferative and proapoptotic effects as well as for its potential in overcoming drug resistance in many kinds of human tumors. Here, we report that AdoMet enhanced the antitumor activity of 5-Fluorouracil (5-FU) in HCT 116p53+/+ and in LoVo CRC cells through the inhibition of autophagy, induced by 5-FU as a cell defense mechanism to escape the drug cytotoxicity. Multiple drug resistance is mainly due to the overexpression of drug efflux pumps, such as P-glycoprotein (P-gp). We demonstrate here that AdoMet was able to revert the 5-FU-induced upregulation of P-gp expression and to decrease levels of acetylated NF-κB, the activated form of NF-κB, the major antiapoptotic factor involved in P-gp-related chemoresistance. Overall, our data show that AdoMet, was able to overcome 5-FU chemoresistance in CRC cells by targeting multiple pathways such as autophagy, P-gp expression, and NF-κB signaling activation and provided important implications for the development of new adjuvant therapies to improve CRC treatment and patient outcomes.

scholarly journals Characterization of the Vibrio cholerae vceCAB Multiple-Drug Resistance Efflux Operon in Escherichia coli

2005 ◽  
Vol 187 (15) ◽  
pp. 5500-5503 ◽  
Author(s):  
Robin C. Woolley ◽  
Govindsamy Vediyappan ◽  
Matthew Anderson ◽  
Melinda Lackey ◽  
Bhagavathi Ramasubramanian ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Drug Resistance ◽  
Vibrio Cholerae ◽  
Efflux Pump ◽  
Multiple Drug Resistance ◽  
Multiple Drug

ABSTRACT Herein, we identify vceC as a component of a vceCAB operon, which codes for the Vibrio cholerae VceAB multiple-drug resistance (MDR) efflux pump, and vceR, which codes for a transcriptional autoregulatory protein that negatively regulates the expression of the vceCAB operon and is modulated by some of the substrates of this MDR efflux pump.

scholarly journals Antisense inhibition of accA in E. coli suppressed luxS expression and increased antibiotic susceptibility

2019 ◽  
Author(s):  
Tatiana Hillman
Keyword(s):  
Drug Resistance ◽  
Antibiotic Susceptibility ◽  
Multiple Drug Resistance ◽  
Cell Envelope ◽  
Medical Community ◽  
Multi Drug Resistance ◽  
Multiple Drug ◽  
Bacterial Cells ◽  
Inner Membrane ◽  
Gram Negative

ABSTRACTBacterial multiple drug resistance is a significant issue for the medical community. Gram-negative bacteria exhibit higher rates of multi-drug resistance, partly due to the impermeability of the Gram-negative bacterial cell wall and double-membrane cell envelope, which limits the internal accumulation of antibiotic agents. The outer lipopolysaccharide membrane regulates the transport of hydrophobic molecules, while the inner phospholipid membrane controls influx of hydrophilic particles. In Escherichia coli, the gene accA produces the acetyl-CoA carboxylase transferase enzyme required for catalyzing synthesis of fatty acids and phospholipids that compose the inner membrane. To increase antibiotic susceptibility and decrease growth, this study interrupted fatty acid synthesis and disrupted the composition of the inner membrane through inhibiting the gene accA with antisense RNA. This inhibition suppressed expression of luxS, a vital virulence factor that regulates cell growth, transfers intercellular quorum-sensing signals mediated by autoinducer-2, and is necessary for biofilm formation. Bacterial cells in which accA was inhibited also displayed a greater magnitude of antibiotic susceptibility. These findings confirm accA as a potent target for developing novel antibiotics such as antimicrobial gene therapies.

scholarly journals Survey of socio-demographic prevalence, risk factors and clinical characterization of tuberculosis in Nishtar Hospital Multan.

2016 ◽  
Vol 2 (1) ◽  
pp. 8 ◽  
Author(s):  
Sana Sharif ◽  
Nazar Mohammad Ranjha ◽  
Abdul Majeed ◽  
Ghulam Abbas ◽  
Muhammad Tuqeer Ajmal ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Risk Factors ◽  
Drug Resistance ◽  
Family History ◽  
Alcohol Consumption ◽  
Young People ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
History Of

Tuberculosis is a worldwide health problem affecting one third of world’s population and Pakistan is no exception. In this study, we used a structured and close-ended questionnaire to collect data about socio-demographic prevalence of tuberculosis, its risk factors, multiple drug resistance tuberculosis and clinical characterization of tuberculosis from Nishtar Hospital Multan, Pakistan. Tuberculosis is an infectious disease, affecting young people and females more commonly in Pakistan. Urbanization, illiteracy, poverty, family history of TB, associated immunosuppressive disorders, smoking and alcohol consumption are major drivers of tuberculosis. Multiple drug resistance tuberculosis is also an emerging problem.

scholarly journals Assessment of Murraya koenigii Leaf Extract against New Multiple Drug Resistance Human Enteric Pathogens

2020 ◽  
Vol 32 (10) ◽  
pp. 2647-2652
Author(s):  
Rudrangshu Chatterjee ◽  
Dushyant Singh ◽  
M.L. Aggarwal ◽  
Ajit Varma ◽  
Abhishek Chauhan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Leaf Extract ◽  
Multiple Drug Resistance ◽  
Enteric Bacteria ◽  
Enteric Pathogens ◽  
Multi Drug Resistance ◽  
Multiple Drug ◽  
Bacterial Strains ◽  
Murraya Koenigii ◽  
Gastrointestinal Infections

Sewage waters are the primary habitats to harbour antibiotic resistance bacteria (ARB) especially multi-drug resistance (MDR) human enteric pathogens. Microorganisms acquire resistance towards many commercial antibiotics due to their inappropriate use. In this study, human enteric pathogens were isolated, identified and characterized and shows the resistance against five different clinically significant commonly prescribed antibiotics. The bacterial strains were isolated from different sewage treatment plants located in Delhi city, India. Samples were analyzed for the detection of pathogenic human enteric bacteria through morphological, biochemical and molecular analysis. Methanolic leaf extract of Murraya koenigii showed the significant antibacterial activity against multi drug resistant human enteric pathogens. Thus, Murraya koenigii leaves would be a potential alterantive to antibiotic regimens for the prevention of gastrointestinal infections.

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