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1.
Article in English | MEDLINE | ID: mdl-38778618

ABSTRACT

BACKGROUND: Eliminating and managing L. monocytogenes, L. welshimeri, and L. ivanovii biofilms is a significant problem for food safety, as listeriosis is among the worst foodborne illnesses. METHOD: The Listex P100 bacteriophage's bactericidal and inhibitory properties have been investigated in relation to varying strains of vegetative cells and biofilms of L. monocytogenes, L. welshimeri, and L. ivanovii. RESULTS: The phage concentrations of 109 and 1010 PFU/ml showed strong antibacterial activity against L. monocytogenes, L. welshimeri, and L. ivanovii at both 10°C and 30°C (P<0.05). In 96- well microplate experiments, bacteriophage treatment inhibited biofilm development and reduced biofilm by up to 57.6% (P ≤ 0.05). When compared to controls, Listex P100 bacteriophage significantly reduced the populations of L. monocytogenes, L. welshimeri, and L. ivanovii biofilms on the surfaces of galvanised, stainless steel, and plastic surfaces where holes were produced and the structure of Listeria spp. was disturbed. CONCLUSION: This study clearly demonstrated that L. monocytogenes, L. welshimeri, and L. ivanovii biofilms on galvanised, stainless steel, and plastic surfaces might be removed by using Listex P100 bacteriophage.

2.
Curr Protein Pept Sci ; 24(7): 551-566, 2023.
Article in English | MEDLINE | ID: mdl-37496250

ABSTRACT

As more antibiotics become ineffective due to drug-resistant bacteria, alternative therapies for infections must be prioritized. While pathogenic bacteria are a major threat, they also supply a massive reservoir of potential drugs for treating a wide range of illnesses. The concerning emergence of antimicrobial resistance and the rapidly dwindling therapeutic pipeline need the quick discovery and development of new antibiotics. Despite their great promise for natural product medicine development, pathogenic microorganisms have remained mostly unexplored and understudied. We review the antibacterial activity of specialized metabolites derived from pathogenic bacteria, emphasizing those presently in pre-clinical studies or with promise for medication development. Several atypical biosynthetic pathways are outlined, together with the crucial functions. We also discuss the mechanism of action and antibacterial activities of the antibiotics under consideration. Pathogenic bacteria as a rich source of antibiotics, along with recent advances in genomics and natural product research methods, may usher in a new golden age of antibiotic discovery.


Subject(s)
Anti-Bacterial Agents , Antimicrobial Peptides , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria , Genomics , Drug Development
3.
Curr Drug Targets ; 24(7): 613-625, 2023.
Article in English | MEDLINE | ID: mdl-37211854

ABSTRACT

INTRODUCTION: Salmonellosis, which is typically distinguished by an immediate onset of fever, abdominal pain, diarrhea, nausea, and vomiting, is a bacterial infection caused by Salmonella. The rising incidence of antibiotic resistance in Salmonella Typhimurium is a major worldwide problem, and a better knowledge of the distribution of antibiotic resistance patterns in Salmonella Typhimurium is critical for selecting the best antibiotic for infection treatment. In this work, the efficiency of bacteriophage therapy of vegetative cells and biofilms of S. Typhimurium was investigated. METHODS: Based on their host ranges, five Bacteriophages were chosen for therapy against 22 Salmonella isolates collected from various sources. PSCs1, PSDs1, PSCs2, PSSr1, and PSMc1 phages were found to exhibit potent anti-S. Typhimurium properties. In a 96-well microplate, the efficacy of bacteriophage therapy (105-1011 PFU/mL) against S. Typhimurium biofilm formers was first tested. A bacteriophage treatment (109 PFU/mL) was subsequently applied in the laboratory for 24 hours to minimize Salmonella adhering to the surfaces of gallstones and teeth. In 96-well microplate experiments, bacteriophage treatment inhibited biofilm development and reduced biofilm by up to 63.6% (P ≤ 0.05). RESULT: When compared to controls, bacteriophages (PSCs1, PSDs1, PSCs2, PSSr1, PSMc1) demonstrated a rapid drop in the populations of S. Typhimurium biofilms generated on the surfaces of gallstones and teeth where the structure of the Salmonella bacteria in the biofilm was broken and holes were created. CONCLUSION: Clearly, this study indicated that phages might be employed to eliminate S. Typhimurium biofilms on gallstone and tooth surfaces.


Subject(s)
Bacteriophages , Gallstones , Humans , Gallstones/microbiology , Biofilms , Salmonella typhimurium , Anti-Bacterial Agents/pharmacology
4.
Comb Chem High Throughput Screen ; 26(11): 1945-1959, 2023.
Article in English | MEDLINE | ID: mdl-36366840

ABSTRACT

SARS-CoV-2 is a disease that endangers both human life and the economy. There was an 11- month period of relative evolutionary standstill following the appearance of SARS-CoV-2 in late 2019. However, the emergence of clusters of mutations known as' variants of concern 'with variable viral properties such as transmissibility and antigenicity defined the evolution of SARS-CoV-2. Several efforts have been made in recent months to understand the atomic level properties of SARS-CoV-2. A review of the literature on SARS-CoV-2 mutations is offered in this paper. The critical activities performed by different domains of the SARS-CoV-2 genome throughout the virus's entry into the host and overall viral life cycle are discussed in detail. These structural traits may potentially pave the way for the development of a vaccine and medication to combat the SARS-CoV-2 sickness.


Subject(s)
COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2/genetics , Vaccine Development , Mutation , Phenotype
5.
Curr Protein Pept Sci ; 23(5): 356-368, 2022.
Article in English | MEDLINE | ID: mdl-35786184

ABSTRACT

BACKGROUND: Infection caused by multidrug-resistant K. pneumoniae is regarded as a severe public health concern worldwide, with most countries reporting an increase in fatality rates over time. Efflux pumps are significant determinants of acquired and/or intrinsic resistance in K. pneumoniae. OBJECTIVES: Our aim is to explore efflux-mediated resistance mechanisms in K. pneumoniae by using quantitative real-time PCR in order to evaluate the expression of efflux pump genes (acrA, acrB, oqxA, and oqxB) and pump regulators (marA, soxS, and rarA). METHODS: Efflux pump inhibitor CCCP reduced MIC values of ciprofloxacin by 2 to 64-fold in 43/46 (93%) of MDR-K. pneumoniae isolates. RESULTS: Compared to the control strain (untreated one), our results demonstrated that acrA, acrB, oqxA, oqxB, marA, soxS, and rarA were overexpressed in 29 (63%), 24 (52%), 29 (63%), 24 (52%), 17 (37%), 16 (35%), and 16 (35%) of K. pneumoniae isolates, respectively. Additionally, a positive correlation was established between the expressions of acrAB and marA (r = 0.50, r = 0.45, respectively) and oqxAB and rarA (r = 0.462912, r = 0.519354, respectively). CONCLUSION: Ciprofloxacin resistance was caused by overexpression of the efflux pump genes acrAB and oqxAB, as well as the transcriptional regulators marA, soxS, and rarA in clinical isolates of K. pneumonia.


Subject(s)
Drug Resistance, Bacterial , Klebsiella pneumoniae , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology , Ciprofloxacin/pharmacology , Drug Resistance, Bacterial/genetics , Humans , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Microbial Sensitivity Tests
6.
Pharmacol Rep ; 73(1): 1-16, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32946075

ABSTRACT

The discovery of antibiotics ought to have ended the issue of bacterial infections, but this was not the case as it has led to the evolution of various mechanisms of bacterial resistance against various antibiotics. The efflux pump remains one of the mechanisms through which organisms develop resistance against antibiotics; this is because organisms can extrude most of the clinically relevant antibiotics from the interior cell environment to the exterior environment via the efflux pumps. Efflux pumps are thought to contribute significantly to biofilm formation as highlighted by various studies. Therefore, the inhibition of these efflux pumps can be a potential way of improving the activity of antibiotics, particularly now that the discovery of novel antibiotics is becoming tedious. Efflux pump inhibitors (EPIs) are molecules that can inhibit efflux pumps; they have been considered potential therapeutic agents for rejuvenating the activity of antibiotics that have already lost their activity against bacteria. However, studies are yet to determine the specific substrates for such pumps; the effect of altered efflux activity of these pumps on biofilm formation is still being investigated. A clear knowledge of the involvement of efflux pumps in biofilm development could aid in developing new agents that can interfere with their function and help to prevent biofilms formation; thereby, improving the outcome of treatment strategies. This review focuses on the novel update of EPIs and discusses the evidence of the roles of efflux pumps in biofilm formation; the potential approaches towards overcoming the increasing problem of biofilm-based infections are also discussed.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/drug effects , Membrane Transport Proteins/drug effects , Animals , Bacteria/drug effects , Biofilms/drug effects , Humans
7.
Mini Rev Med Chem ; 20(18): 1908-1916, 2020.
Article in English | MEDLINE | ID: mdl-32811410

ABSTRACT

The need for new therapeutics and drug delivery systems has become necessary owing to the public health concern associated with the emergence of multidrug-resistant microorganisms. Among the newly discovered therapeutic agents is cefiderocol, which was discovered by Shionogi Company, Japan as an injectable siderophore cephalosporin. Just like the other ß-lactam antibiotics, cefiderocol exhibits antibacterial activity via cell wall synthesis inhibition, especially in Gram negative bacteria (GNB); it binds to the penicillin-binding proteins, but its unique attribute is that it crosses the periplasmic space of bacteria owing to its siderophore-like attribute; it also resists the activity of ß-lactamases. Among all the synthesized compounds with the modified C-7 side chain, cefiderocol (3) presented the best and well-balanced activity against multi-drug resistant (MDR) Gram negative bacteria, including those that are resistant to carbapenem. In this article, an overview of the recent studies on cefiderocol was presented.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cephalosporins/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Gram-Negative Bacteria/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Cephalosporins/chemical synthesis , Cephalosporins/chemistry , Microbial Sensitivity Tests , Molecular Structure , Cefiderocol
8.
Curr Drug Targets ; 21(13): 1326-1343, 2020.
Article in English | MEDLINE | ID: mdl-32564749

ABSTRACT

Iron, which is described as the most basic component found in nature, is hard to be assimilated by microorganisms. It has become increasingly complicated to obtain iron from nature as iron (II) in the presence of oxygen oxidized to press (III) oxide and hydroxide, becoming unsolvable at neutral pH. Microorganisms appeared to produce organic molecules known as siderophores in order to overcome this condition. Siderophore's essential function is to connect with iron (II) and make it dissolvable and enable cell absorption. These siderophores, apart from iron particles, have the ability to chelate various other metal particles that have collocated away to focus the use of siderophores on wound care items. There is a severe clash between the host and the bacterial pathogens during infection. By producing siderophores, small ferric iron-binding molecules, microorganisms obtain iron. In response, host immune cells produce lipocalin 2 to prevent bacterial reuptake of siderophores loaded with iron. Some bacteria are thought to produce lipocalin 2-resistant siderophores to counter this risk. The aim of this article is to discuss the recently described roles and applications of bacterial siderophore.


Subject(s)
Bacteria/metabolism , Siderophores/biosynthesis , Siderophores/physiology , Animals , Anti-Bacterial Agents/chemistry , Host-Pathogen Interactions , Humans , Iron/metabolism , Lipocalin-2/metabolism , Mitophagy , Siderophores/chemistry , Siderophores/therapeutic use , beta-Lactams/chemistry
9.
Mini Rev Med Chem ; 18(6): 507-526, 2018.
Article in English | MEDLINE | ID: mdl-28425868

ABSTRACT

Four distinguished although overlying stages make up the methodical procedure of wound healing, which are hemostasis, inflammation, proliferation and remodelling. Multiple sclerosis (MS) is described as an incessant inflammatory central nervous system disease, and is linked with neurodegeneration, demyelination, as well as susceptibility to oxidative pressure. Obesity signifies a swiftly developing danger to the wellbeing of populations in a rising number of nations. Usually called diabetes mellitus (DM) by medical practitioners, diabetes details a collection of metabolic diseases within which the individual has raised blood glucose, either due to an insufficiency of insulin generation, or the lack of suitable response by the body to insulin, or both. Conventionally, the pomegranate, as well as its flowers, leaves, fruit juice and tree bark, has been applied in the treatment of conditions including acidosis, haemorrhage, diarrhoea and microbial contagions. Extracts of pomegranate have been established to contain intense anti-inflammatory, antioxidant as well as antitumor features in vivo as well as ex vivo. Of late, beneficial consequences of decrease of fat have been illustrated employing the pomegranate as well as its extracts. Several of the favourable consequences are associated with the availability of anthocyanins, tannins, and considerably elevated amounts of antioxidants, as well as flavonoids and polyphenols. A summary of the endeavours applied to deal with the possible advantages of the pomegranate towards healing wounds, Alzheimer's disease (AD), diabetes mellitus (DM) and obesity, as well as an appraisal of the efficiency of intervention through the pomegranate and its extracts is provided in this article.


Subject(s)
Diabetes Mellitus/drug therapy , Lythraceae , Neurodegenerative Diseases/drug therapy , Obesity/drug therapy , Plant Extracts/therapeutic use , Wound Healing/drug effects , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/therapeutic use , Antioxidants/chemistry , Antioxidants/therapeutic use , Fruit/chemistry , Humans , Hydrolyzable Tannins/chemistry , Hydrolyzable Tannins/therapeutic use , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/therapeutic use , Lythraceae/chemistry , Plant Extracts/chemistry
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