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

2019 ◽  
Author(s):  
Tatiana Hillman

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.

2021 ◽  
Vol 12 ◽  
Author(s):  
Sofia Mindlin ◽  
Olga Maslova ◽  
Alexey Beletsky ◽  
Varvara Nurmukanova ◽  
Zhiyong Zong ◽  
...  

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.


2021 ◽  
Author(s):  
Jignasha T. Thumar ◽  
Nisha Trivedi

The overuse of antibiotics has resulted in the development of drug resistant, a major problem in disease curing processes i.e. development of drug resistance. The World Health Organization (WHO) released its first list of the most concerning pathogens for human health in 2017 which suggested that there are total 12 bacterial families which have developed multiple drug resistance and for which novel antibiotics are required immediately (WHO 2017). There is a requirement to explore some novel compounds to overcome this issue. Thus our study aimed at exploration of marine actinomycetes as a valuable resource for novel products with antimicrobial properties. The halophilic actinomycete Nocardiopsis_sp. Al-H10-1 (KF384482) was isolated from saline water (20 m away from shore) of Alang coast (Gulf of Khambhat), Bhavnagar, Gujarat, India. The isolate Al-H10-1 was identified as Nocardiopsis sp. through rigorous morphological and cultural characteristics; the species was confirmed through 16s rRNA phylogenetic analysis. The antimicrobial potential of Nocardiopsis sp. Al-H10-1 was assessed against a range of Gram-positive and Gram-negative bacteria as well as three fungi, there it demonstrated antimicrobial activity against four Gram negative bacteria and one Gram positive bacteria. Further active antimicrobial compounds present in ethyl acetate extract was identified using Gas Chromatography-Mass Spectroscopy (GC-MS). GC-MS analysis showed the presence of 17 compounds which included antimicrobial compounds like 2, 4-bis (1, 1-dimethylethyl)-Phenol, Dibutyl phthalate as well as various types of alkanes and their derivatives.


2021 ◽  
Vol 22 (17) ◽  
pp. 9286
Author(s):  
Laura Mosca ◽  
Martina Pagano ◽  
Luigi Borzacchiello ◽  
Luigi Mele ◽  
Annapina Russo ◽  
...  

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.


2009 ◽  
Vol 6 (3) ◽  
pp. 549-552
Author(s):  
Baghdad Science Journal

60 cases of Bacteremia were documented at Ibn Al-Baladi hospital during 6 months (1-1-2002 to 1-7-2002), with an incidence of 5.2 were gram-negative organisms and most common one was Salmonella and Klebsiella. Incidence was significantly higher in male than female .Antimicrobial sensitivity tests revealed that isolated bacteria are with multiple drug resistance to commonly used antimicrobial agents. Salmonella showed high resistance to cephaloxin, co-trimoxazole and amoxicillin and also Klebsiella showed resistance to cephaloxin and amoxicillin.


2020 ◽  
Vol 32 (10) ◽  
pp. 2647-2652
Author(s):  
Rudrangshu Chatterjee ◽  
Dushyant Singh ◽  
M.L. Aggarwal ◽  
Ajit Varma ◽  
Abhishek Chauhan ◽  
...  

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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