Indole-based novel small molecules for the modulation of bacterial signalling pathways

2015 ◽  
Vol 13 (3) ◽  
pp. 925-937 ◽  
Author(s):  
Nripendra Nath Biswas ◽  
Samuel K. Kutty ◽  
Nicolas Barraud ◽  
George M. Iskander ◽  
Renate Griffith ◽  
...  

Indole basedN-acylatedl-homoserine lactone (AHL) mimics were developed as quorum sensing (QS) inhibitors for Gram-negative bacteriaPseudomonas aeruginosaand can be used as novel antimicrobial agents.

2012 ◽  
Vol 37 (2) ◽  
pp. 315-318 ◽  
Author(s):  
Chigusa Okano ◽  
Marina Arai ◽  
Eri Nasuno ◽  
Ken-ichi Iimura ◽  
Tomohiro Morohoshi ◽  
...  

2006 ◽  
Vol 89 (3-4) ◽  
pp. 167-211 ◽  
Author(s):  
Debra Smith ◽  
Jin-Hong Wang ◽  
Jane E. Swatton ◽  
Peter Davenport ◽  
Bianca Price ◽  
...  

Author(s):  
Oludare Temitope Osuntokun

Nose/Face masks are physical barriers to respiratory droplets that may enter through the nose and mouth to cause infections in the respiratory tract. The study was determined and assess the presence of Gram-negative bacteria in used home-made and surgical nose mask by residents of Akungba-Akoko Ondo State and to determine the antimicrobial susceptibility and resistant profile of the isolated bacteria to eight (8) different antimicrobial agents. The antimicrobial analysis were performed using standard microbiological and biochemical methods. Antimicrobial Susceptibility test of all identified isolates to antimicrobial agents were determined using the standard Kirby-Bauer disk diffusion method. The Gram-negative bacteria that were detected from the used home-made and surgical nose mask in this study include: Haemophilus influenza, Proteus mirabilis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia. During this study, all the Gram-negative bacteria isolates were resistant to Ciproflox in both used home-made and surgical nose mask. All isolates were also resistant to Ampicilin, Augmentin, Septrin and Streptomycin. In this study, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were isolated organism from used home-made nose mask, it was observed that Escherichia coli were resistant to Augmentin, Tarivid, Ciproflox, Gentamycin, and Reflaxine, and Pseudomonas aeruginosa were resistant to Tarivid, Ciproflox, and Nalidixic acid between 20 mm and 24 mm zones of inhibition respectively. Haemophilus influenza, Pseudomonas aeruginosa, Escherichia coli and Proteus mirabilis were isolated organism from used surgical nose mask. It was observed that all isolated organisms from the used surgical nose/face mask were resistant to Augmentin and Gentamycin between 20 and 24 mm zones of inhibition respectively. Klebsiella pneumoniae were isolated from both used home-made and surgical nose/face mask and were found to be resistant to Streptomycin, Septrin, Ampicilin, and Gentamicin between 20 to 22 mm zones of inhibition respectively. Proteus mirabilis were isolated from used surgical nose/face mask,        they were found to be resistant to Ciproflox at 21mm zones of inhibition. Haemophilus influenza were resistant to Ampicilin, Septrin, Streptomycin, and Augmentin at 23 mm zones of inhibition. Isolates from used both home-made and surgical nose/face mask were subjected to modified and synergized antibiotics, it was observed that the isolates from both used home-made and surgical nose mask were resistant to all modified and synergized antibiotics between 20 and 25 mm zones of inhibition respectively. The result of this study validates the potency of  Gram negative bacteria isolated from used both home-made and surgical nose/face mask and the degree of invasion and evasiveness, thereby causing various degrees of infections and a false sense of protection against SARS-CoV-2 (COVID-19). Finding from this research recommends a stringent measures were needed to be implemented, to halt and combat this revenging situation especially in the new era of mutating SARS-CoV-2 Virus not only in Nigeria, worldwide at large.


2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Christopher Longshaw ◽  
Davide Manissero ◽  
Masakatsu Tsuji ◽  
Roger Echols ◽  
Yoshinori Yamano

Abstract Objectives Many carbapenem-resistant (CR) Gram-negative (GN) pathogens exhibit MDR, meaning few therapeutic options are available for CR-GN infections. Cefiderocol, a siderophore cephalosporin, has demonstrated in vitro efficacy against CR-GN bacteria. In the SIDERO-CR-2014–2016 surveillance study, European clinical isolates comprising carbapenem-non-susceptible (CarbNS) Enterobacterales and MDR non-fermenters were tested against cefiderocol and comparators. Methods Cefiderocol MICs were determined using iron-depleted CAMHB, and comparators using CAMHB, per recommended CLSI methodology. Carbapenemase gene profiles were determined using PCR. Results Isolates (N = 870) from 23 European countries comprised CarbNS Enterobacterales (n = 457), MDR Pseudomonas aeruginosa (n = 177) and MDR Acinetobacter baumannii (n = 236). The most common carbapenemases were KPC (52%), OXA-48-like (19%), VIM (14%) and NDM (8%) in Enterobacterales, VIM (41%) in P. aeruginosa and OXA-23-like (57%) and OXA-24/40-like (37%) in A. baumannii. Most carbapenemase-producing isolates (65%) co-carried ESBLs. Approximately half of P. aeruginosa isolates were negative for carbapenemases, compared with 10% of Enterobacterales and 3% of A. baumannii. A similar proportion of Enterobacterales were susceptible to cefiderocol (81.6%; 79.0% of VIM producers; 51.4% of NDM producers; based on EUCAST breakpoint values) compared with comparator antimicrobial agents, including colistin (76.4%; 93.5% of VIM producers; 78.4% of NDM producers) and ceftazidime/avibactam (76.6%; 1.6% of VIM producers; 2.7% of NDM producers). Of P. aeruginosa isolates, 98.3% were susceptible to cefiderocol (100% of VIM producers), similar to colistin (100%). Against A. baumannii, 94.9% had cefiderocol MIC ≤2 mg/L and 93.6% of isolates were susceptible to colistin. Conclusions Cefiderocol demonstrated potent activity against CarbNS and MDR GN bacteria, including non-fermenters and a wide variety of MBL- and serine-β-lactamase-producing strains.


2019 ◽  
Vol 35 (4) ◽  
pp. 1248-1253
Author(s):  
Lubna Swellmeen ◽  
Amal Uzrail ◽  
Rand Shahin ◽  
Yusuf AL-Hiari

Fluoroquinolones are well known to have an anti-infective action. In the present study we described the synthesis of novel florouquinolones derivative as antimicrobial agent. The biological test highlighted a good inhibitory activity for the 7-Chloro-1-Alkyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derived synthons especially against pathogenic Gram-negative bacteria (Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Streptococcus agalactiae). The binding interactions were monitored and could explain the good inhibitory activity of the synthesized derivatives of florouquinolones.


2016 ◽  
Author(s):  
Vijay Kothari ◽  
Pooja Patel ◽  
Chinmayi Joshi ◽  
Brijesh Mishra ◽  
Shashikant Dubey ◽  
...  

AbstractEffect of nine different mono-frequency sound stimuli on two gram-negative bacteria (Pseudomonas aeruginosa and Serratia marcescens) was investigated. Frequency of the test sound ranged from 100 Hz to 2,000 Hz. Both the test bacteria responded differently to sonic stimulation. Sound corresponding to 600 HZ caused a notable reduction in quorum sensing (QS) regulated production of the pigment pyoverdine by P. aeruginosa. 400 Hz sound affected prodigiosin production by S. marcescens the most. 500 Hz sound could enhance prodigiosin production without affecting growth of the producing bacterium, suggesting the effect purely to be QS modulatory. This study has demonstrated the capacity of the sound waves of affecting bacterial growth and quorum sensing regulated metabolite production.


Biofilms ◽  
2005 ◽  
Vol 2 (1) ◽  
pp. 37-61 ◽  
Author(s):  
M. Hentzer ◽  
L. Eberl ◽  
M. Givskov

In nature, bacteria are able to form complex surface-attached communities called biofilms. Microbial biofilms pose a particular problem in many human infections because of an inherent tolerance to antimicrobial agents and host immune killing and clearance. We have used complementary DNA (cDNA) microarray technology to identify Pseudomonas aeruginosa genes that are differentially expressed in growing and developing biofilms. Our study shows that, when compared with planktonic bacteria, gene expression profiles of biofilm cells have the highest resemblance to the profiles of stationary-phase cells. We suggest that the process of biofilm development involves a series of adaptive responses including those to anaerobic and iron-limitation stresses, rather than being associated with a unique biofilm developmental program. Mapping of quorum-sensing regulated genes in a P. aeruginosa biofilm identified a set of N-acyl homoserine lactone (AHL)-dependent genes that are exclusively expressed in sessile cells. One of these genes, pvdQ, encodes an AHL acylase that degrades long-acyl but not short-acyl AHLs. This result may provide an explanation for the previous finding that the level of long-acyl AHLs is greatly reduced in P. aeruginosa biofilm cells as compared with their planktonic counterparts. Furthermore, we present evidence that quorum sensing is participating in the control of iron-limitation responses in the biofilm cells.


2012 ◽  
Vol 56 (12) ◽  
pp. 6088-6094 ◽  
Author(s):  
Li Ma ◽  
Xiangyang Liu ◽  
Haihua Liang ◽  
Yizhou Che ◽  
Caixia Chen ◽  
...  

ABSTRACTInPseudomonas aeruginosa, the quorum-sensing (QS) system is closely related to biofilm formation. We previously demonstrated that 14-alpha-lipoyl andrographolide (AL-1) has synergistic effects on antibiofilm and antivirulence factors (pyocyanin and exopolysaccharide) ofP. aeruginosawhen combined with conventional antibiotics, while it has little inhibitory effect on its growth. However, its molecular mechanism remains elusive. Here we investigated the effect of AL-1 on QS systems, especially the Las and Rhl systems. This investigation showed that AL-1 can inhibit LasR–3-oxo-C12-homoserine lactone (HSL) interactions and repress the transcriptional level of QS-regulated genes. Reverse transcription (RT)-PCR data showed that AL-1 significantly reduced the expression levels oflasR,lasI,rhlR, andrhlIin a dose-dependent manner. AL-1 not only decreased the expression level of Psl, which is positively regulated by the Las system, but also increased the level of secretion of ExoS, which is negatively regulated by the Rhl system, indicating that AL-1 has multiple effects on both the Las and Rhl systems. It is no wonder that AL-1 showed synergistic effects with other antimicrobial agents in the treatment ofP. aeruginosainfections.


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