bacterial drug resistance

The problem of nosocomial infection is seriously escalating. Bacterial vaccines are indispensable for preventing infections caused by multi-drug resistant organisms. Some researchers have put forward the use of hydrogen peroxide (H2 O2 ) as a new technology platform for virus deactivation. This deactivated virus can induce the number of CD8+ T lymphocytes, which can enhance antiviral responses. Although, H2 O2 treatment has been rarely reported on the exploration of bacterial deactivation, H2 O2 deactivation of whole-cell bacteria could be a potential novel approach for bacterial vaccine development...

Optochin, a cinchona alkaloid derivative discovered over 100 years ago, possesses highly selective antibacterial activity towards Streptococcus pneumoniae. Pneumococcal disease remains the leading source of bacterial pneumonia and meningitis worldwide. The structure activity relationships of optochin were examined through modification to both the quinoline and quinuclidine subunits, which led to the identification of analogue 48 with substantially improved activity. Resistance and molecular modeling studies indicate 48 likely binds to the c-ring of ATP synthase near the conserved glutamate 52 ion binding site while mechanistic studies demonstrated 48 causes cytoplasmic acidification...

Curcumin as a flavonoid from the rhizome of Curcuma longa has antibacterial, antiviral and antifungal activity. Multidrug resistance in pathogenic bacteria is continuously increasing in hospitals. The aim of this study was to investigate the effect of curcumin encapsulated in micellar/polymersome nanoparticles as an efflux pump inhibitor (EPI) on the expression of mexX and oprM genes in curcumin-treated and -untreated isolates of Pseudomonas aeruginosa. Clinical isolates of Pseudomonas aeruginosa were treated with ciprofloxacin (sub-MICs) alone and/or in combination with curcumin-encapsulated in micellar/polymersome nanoparticles...

Colistin resistance in Enterobacteriaceae especially Klebsiella pneumoniae and Escherichia coli is driving the evolution of pan drug resistant strains. Screening a library of 13 plant nutraceuticals led to the identification of acetyl shikonin and ursolic acid, which exhibited synergy with colistin against extremely drug resistant (XDR) clinical strains of E. coli (U3790) and K. pneumoniae (BC936). Ursolic acid caused a significant colistin MIC reversal of 16-fold in U3790 and 4-fold in BC936 strains. Ursolic acid also potentiated the bactericidal effect of colistin against both U3790 and BC936 by causing ~ 4 to 4...

The accumulation of bacteria on surfaces is currently one of the greatest concerns for the management of proper healthcare systems, water and energy. Here, we describe the mechanism by which a single peptide forms two pH-dependent supramolecular particles that resist bacterial contamination. By using NMR and molecular dynamics (MD), we determined the structures of the peptide monomers and showed the forces directing the self-assembly of each structure under different conditions. These peptide assemblies change the characteristics of bare glass and confer it with the ability to prevent biofilm formation...

Microsomal cytochrome P450 (CYP) enzymes, isolated from recombinant bacterial/insect/yeast cells, are extensively used for drug metabolism studies. However, they may not always portray how a developmental drug would behave in human cells with intact intracellular transport mechanisms. This study emphasizes the usefulness of human HEK293 kidney cells, grown in 'suspension' for expression of CYPs, in finding potent CYP1A1/CYP1B1 inhibitors, as possible anticancer agents. With live cell-based assays, quinazolinones 9i/9b were found to be selective CYP1A1/CYP1B1 inhibitors with IC50 values of 30/21 nM, and > 150-fold selectivity over CYP2/3 enzymes, whereas they were far less active using commercially-available CYP1A1/CYP1B1 microsomal enzymes (IC50 , >10/1...

Bacterial persisters are a subpopulation of cells that exhibit phenotypic resistance during exposure to a lethal dose of antibiotics. They are difficult to target and thought to contribute to the long treatment duration required for tuberculosis. Understanding the molecular and cellular biology of persisters is critical to finding new tuberculosis drugs that shorten treatment. This review focuses on mycobacterial persisters and describes the challenges they pose in tuberculosis therapy, their characteristics and formation, how persistence leads to resistance, and the current approaches being used to target persisters within mycobacterial drug discovery...

Introduction: Shigellosis is a significant global human health problem, and Shigella is in charge of almost 165 million cases of this disease annually, of whom 163 million cases are in developing countries and 1.5 million cases are in developed countries. The main aims of the current survey were to identify Shigella spp. isolated from diarrheal patients by conventional biochemical tests, determine the antimicrobial susceptibility profiles by disk diffusion method, and detect the ipaH gene using the PCR assay...

Background and Aim: The extensive use of antimicrobials in poultry has led to an increase in bacterial multidrug resistance, and the emergence of multidrug-resistant nontyphoidal Salmonella is a global problem. This study was performed to detect antibiotic-resistant Salmonella serovars in poultry farming and processing environment. Materials and Methods: A total of 956 various samples, comprising 432 farm origin, 324 poultry processing stage wise and environmental, and 154 product processing stages and environmental samples, were collected from poultry farms and processing units located in and around Mumbai city...

Surgical sutures are vulnerable to bacterial infections and biofilm formation. At the suture site, pain and undesirable, excess inflammation are additionally detrimental to wound healing. The development of a polymerized cyclodextrin (pCD) coated surgical suture introduces the capability to locally deliver both anti-inflammatory and anti-microbial drugs throughout the phases of acute and chronic healing. Local delivery allows for the improvement of wound healing while reducing related systemic side effects and drug resistance...

A series of aminothiazolyl norfloxacin analogues as a new type of potential antimicrobial agents were synthesized and screened for their antimicrobial activities. Most of the prepared compounds exhibited excellent inhibitory efficiencies. Especially, norfloxacin analogue II-c displayed superior antimicrobial activities against K. pneumoniae and C. albicans with MIC values of 0.005 and 0.010 mM to reference drugs, respectively. This compound not only showed broad antimicrobial spectrum, rapid bactericidal efficacy and strong enzymes inhibitory potency including DNA gyrase and chitin synthase (CHS), low toxicity against mammalian cells and no obvious propensity to trigger the development of bacterial resistance, but also exerted efficient membrane permeability, and could effectively intercalate into K...

Catheters are highly prone to bacterial colonization during catheterization. Catheter-associated urinary tract infections caused by Klebsiella pneumoniae are significantly associated with high morbidity. Klebsiella pneumoniae is the prominent cause of infections in individuals with indwelling urinary catheters. Hence, the present work was aimed to find the efficacy of caprylic acid (CAP), a non-antibiotic natural compound to control Klebsiella pneumonaie biofilm. Upon 24 hours treatment of caprylic acid at 0...

Phage therapy, long overshadowed by chemical antibiotics, is garnering renewed interest in Western medicine. This stems from the rise in frequency of multi-drug-resistant bacterial infections in humans. There also have been recent case reports of phage therapy demonstrating clinical utility in resolving these otherwise intractable infections. Nevertheless, bacteria can readily evolve phage resistance too, making it crucial for modern phage therapy to develop strategies to capitalize on this inevitability. Here, we review the history of phage therapy research...

Background The increasing number of multi-drug resistant (MDR) bacteria provides enormous challenges for choosing an appropriate antibiotic therapy in the early phase of sepsis. While bacterial identification has been greatly accelerated by the introduction of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), the antibiotic susceptibility testing (AST) remains time-consuming. Here, we present a rapid susceptibility testing method for testing Gram-negative bacteria, exemplarily validated for Escherichia coli and Klebsiella spp...

Antibiotic resistance in pathogenic bacteria has emerged as a big challenge to human and animal health and significant economy loss worldwide. Development of novel strategies to tackle antibiotic resistance is of the utmost priority. In this study, we combined glutathione (GSH), a master antioxidant in all mammalian cells, and nitric oxide, a proven biofilm-dispersing agent, to produce GSNO. Resazurin biofilm viability assay, crystal violet biofilm assay, and confocal microscopy techniques showed that GSNO disrupted biofilms of both P...

Aminoglycoside acetyltransferases are important determinants of resistance to aminoglycoside antibiotics in most bacterial genera. In mycobacteria, however, aminoglycoside acetyltransferases contribute only partially to aminoglycoside susceptibility since they are related with low level resistance to these antibiotics (while high level aminoglycoside resistance is due to mutations in the ribosome). Instead, aminoglycoside acetyltransferases contribute to other bacterial functions, and this can explain its widespread presence along species of genus Mycobacterium ...

The emergence of multidrug resistant (MDR) infections and the shortage of new therapeutic options have made colistin, a polymyxin antibiotic, the main option for the treatment of MDR Gram-negative bacterial infections in the last decade. However, the rapid onset of renal damage often prevents the achievement of optimal therapeutic doses and/or forces the physicians to interrupt the therapy, increasing the risk of drug resistance. The proper management of colistin-induced nephrotoxicity remains challenging, mostly because the investigation of the cellular and molecular pharmacology of this drug, off the market for decades, has been largely neglected...

Melioidosis associated with opportunistic pathogen Burkholderia pseudomallei imparts a huge medical burden in Southeast Asia and Australia. At present there is no available human vaccine that protects against B. pseudomallei infection and antibiotic treatments are limited particularly for drug-resistant strains and bacteria in biofilm forms. Biofilm forming bacteria exhibit phenotypic features drastically different to their planktonic states, often exhibiting a diminished response to antimicrobial therapies...

The numbers of multiple drug-resistant Gram-negative bacterial infections are rising worldwide. The threat is increased by the lack of new antibiotics, so clinicians are turning to older drugs previously abandoned due to their recognized toxicity, such as colistin. However, the need to avoid kidney toxicity from colistin has led to its topical use. We present the case of a patient with type I cardiorenal syndrome with cystitis due to multiple drug-resistant Pseudomonas aeruginosa who was successfully treated with intravesical instillation of colistin...

BACKGROUND: Metabolites obtained from the marine microorganisms were known for their important role in microbial inhibition. Interestingly, bioprospecting of secondary metabolites from marine derived actinomycetes has huge demand especially in the treatment of multi drug resistant clinical pathogens. The present study subjected towards the identification of promising antimicrobial actinomycetes from the Arabian Gulf regions and metabolic profiling of the crude organic solvent extract by chromatographic techniques...