scholarly journals Two Hits Are Better than One: Membrane-Active and DNA Binding-Related Double-Action Mechanism of NK-18, a Novel Antimicrobial Peptide Derived from Mammalian NK-Lysin

2012 ◽  
Vol 57 (1) ◽  
pp. 220-228 ◽  
Author(s):  
Jiexi Yan ◽  
Kairong Wang ◽  
Wen Dang ◽  
Ru Chen ◽  
Junqiu Xie ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Cytotoxic T Cells ◽  
Multidrug Resistant ◽  
Chemotherapeutic Agents ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Content Type ◽  
New Strategy ◽  
Conventional Antibiotics ◽  
Double Targets

ABSTRACTThe extensive use and misuse of antibiotics in medicine result in the emergence of multidrug-resistant bacteria, creating an urgent need for the development of new chemotherapeutic agents. Nowadays, antimicrobial peptides are widely recognized as a class of promising candidates with activity against multidrug-resistant bacteria. NK-18 is a truncated peptide derived from NK-Lysin, an effector of cytotoxic T cells and natural killer cells. In this study, we studied the antibacterial mechanism of action of NK-18. The results revealed that NK-18 has potent antibacterial activity againstEscherichia coliandStaphylococcus aureus. According to our findings, NK-18 is membrane active and its target of action is not only the bacterial membrane but also the DNA in the cytoplasm. The double targets of NK-18 make it difficult for bacteria to generate resistance, which may present a new strategy to defend against multidrug-resistant bacteria and provide a new lead in the design of potent antimicrobial peptides with therapeutic application in the presence of increasing resistance to conventional antibiotics.

scholarly journals Environmental Spread of New Delhi Metallo-β-Lactamase-1-Producing Multidrug-Resistant Bacteria in Dhaka, Bangladesh

2017 ◽  
Vol 83 (15) ◽  
Author(s):  
Mohammad Aminul Islam ◽  
Moydul Islam ◽  
Rashedul Hasan ◽  
M. Iqbal Hossain ◽  
Ashikun Nabi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Tap Water ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
New Delhi ◽  
Multidrug Resistant Bacteria ◽  
Content Type ◽  
Wastewater Samples

ABSTRACT Resistance to carbapenem antibiotics through the production of New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an emerging challenge in the treatment of bacterial infections. To monitor the possible source of the spread of these organisms in Dhaka, Bangladesh, we conducted a comparative analysis of wastewater samples from hospital-adjacent areas (HAR) and from community areas (COM), as well as public tap water samples, for the occurrence and characteristics of NDM-1-producing bacteria. Of 72 HAR samples tested, 51 (71%) samples were positive for NDM-1-producing bacteria, as evidenced by phenotypic tests and the presence of the bla NDM-1 gene, compared to 5 of 41 (12.1%) samples from COM samples (P < 0.001). All tap water samples were negative for NDM-1-producing bacteria. Klebsiella pneumoniae (44%) was the predominant bacterial species among bla NDM-1-positive isolates, followed by Escherichia coli (29%), Acinetobacter spp. (15%), and Enterobacter spp. (9%). These bacteria were also positive for one or more other antibiotic resistance genes, including bla CTX-M-1 (80%), bla CTX-M-15 (63%), bla TEM (76%), bla SHV (33%), bla CMY-2 (16%), bla OXA-48-like (2%), bla OXA-1 (53%), and bla OXA-47-like (60%) genes. Around 40% of the isolates contained a qnr gene, while 50% had 16S rRNA methylase genes. The majority of isolates hosted multiple plasmids, and plasmids of 30 to 50 MDa carrying bla NDM-1 were self-transmissible. Our results highlight a number of issues related to the characteristics and source of spread of multidrug-resistant bacteria as a potential public health threat. In view of the existing practice of discharging untreated liquid waste into the environment, hospitals in Dhaka city contribute to the potential dissemination of NDM-1-producing bacteria into the community. IMPORTANCE Infections caused by carbapenemase-producing Enterobacteriaceae are extremely difficult to manage due to their marked resistance to a wide range of antibiotics. NDM-1 is the most recently described carbapenemase, and the bla NDM-1 gene, which encodes NDM-1, is located on self-transmissible plasmids that also carry a considerable number of other antibiotic resistance genes. The present study shows a high prevalence of NDM-1-producing organisms in the wastewater samples from hospital-adjacent areas as a potential source for the spread of these organisms to community areas in Dhaka, Bangladesh. The study also examines the characteristics of the isolates and their potential to horizontally transmit the resistance determinants. The significance of our research is in identifying the mode of spread of multiple-antibiotic-resistant organisms, which will allow the development of containment measures, leading to broader impacts in reducing their spread to the community.

Designer protein pseudo-capsids targeting intracellular bacteria

2021 ◽  
Author(s):  
Stephanie Rey ◽  
Nilofar Faruqui ◽  
Alex Hoose ◽  
Camilla Dondi ◽  
Maxim Ryadnov
Keyword(s):  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Intracellular Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Antimicrobial Materials ◽  
Conventional Antibiotics

The emergence of multidrug-resistant bacteria stimulates the search for antimicrobial materials capable of addressing challenges conventional antibiotics fail to address. The ability to target intracellular bacteria remains one of the...

Antimicrobial peptides: an overview of a promising class of therapeutics

2007 ◽  
Vol 2 (1) ◽  
pp. 1-33 ◽  
Author(s):  
Andrea Giuliani ◽  
Giovanna Pirri ◽  
Silvia Nicoletto
Keyword(s):  
Antimicrobial Peptides ◽  
Multidrug Resistant ◽  
Innate Immune ◽  
Resistant Bacteria ◽  
Yeast Fungi ◽  
Wide Range ◽  
New Development ◽  
Catheter Site ◽  
Conventional Antibiotics

AbstractAntibiotic resistance is increasing at a rate that far exceeds the pace of new development of drugs. Antimicrobial peptides, both synthetic and from natural sources, have raised interest as pathogens become resistant against conventional antibiotics. Indeed, one of the major strengths of this class of molecules is their ability to kill multidrug-resistant bacteria. Antimicrobial peptides are relatively small (6 to 100 aminoacids), amphipathic molecules of variable length, sequence and structure with activity against a wide range of microorganisms including bacteria, protozoa, yeast, fungi, viruses and even tumor cells. They usually act through relatively non-specific mechanisms resulting in membranolytic activity but they can also stimulate the innate immune response. Several peptides have already entered pre-clinical and clinical trials for the treatment of catheter site infections, cystic fibrosis, acne, wound healing and patients undergoing stem cell transplantation. We review the advantages of these molecules in clinical applications, their disadvantages including their low in vivo stability, high costs of production and the strategies for their discovery and optimization.

Polymicrobial multidrug-resistant bacteria isolated from street vended fresh fruit juices in Pakistan

2018 ◽  
Vol 120 (6) ◽  
pp. 1358-1365
Author(s):  
Muhammad Hussnain Siddique ◽  
Muhammad Usman Qamar ◽  
Sumreen Hayat ◽  
Bilal Aslam ◽  
Habibullah Nadeem ◽  
...  
Keyword(s):  
Public Health ◽  
Multidrug Resistant ◽  
Fruit Juices ◽  
Fresh Fruit ◽  
Resistant Bacteria ◽  
Local Market ◽  
Multidrug Resistant Bacteria ◽  
Content Type ◽  
Preliminary Identification ◽  
Surface Spread

Purpose The purpose of this paper is to evaluate the prevalence and antibiograms of bacteria isolated from various fresh fruit juices at a local market in Faisalabad. Design/methodology/approach Fresh fruit juice samples (n=125) were randomly collected using aseptic technique. Each sample (10 mL) was serially diluted with 90 mL of sterile peptone water, from 1×10−1 to 1×10−5. Each dilution was then used to inoculate nutrient agar by surface spread plating. Aerobic colony counts (ACCs) were determined by colony counting. The isolates were sub-cultured on blood and MacConkey agar. Preliminary identification was achieved on the basis of colony morphology and culture characteristic, and confirmed by API® 20E, 20NE, and API® Staph testing. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer disk diffusion assay, per CLSI 2015 guidelines. Findings The mean ACC ranged from 2.0×106 CFU/mL to 4.93×106 CFU/mL, with the highest ACC determined for orange juice. Overall, 153 polymicrobial were identified in 125 samples; 103 of these were Gram-negative rods (GNR) and 28 were Gram-positive cocci (GPC). Escherichia coli (n=38), Klebsiella pneumoniae (n=32) and Pseudomonas aeruginosa (n=24) were the predominant GNR; Staphylococcus aureus (n=28) was the predominant GPC. Antibiogram analysis revealed that all GNR were resistant to ampicillin. However, most E. coli isolates were resistant to ceftazidime (72.4 percent of isolates), and ceftriaxone and cefepime (68.9 percent), while most K. pneumoniae isolates were resistant to cefepime (72 percent) and ceftriaxone (64 percent). All S. aureus isolates were resistant to penicillin, while most (64 percent) were resistant to piperacillin; the most effective drugs against bacteria were vancomycin and imipenem. Practical implications The findings suggest that the local government regulatory food and public health authorities should take immediate emergency measures. Appropriate surveillance studies and periodic monitoring of food items should be regularly performed to safeguard public health. Originality/value The current study revealed the prevalence of multidrug-resistant bacteria in freshly prepared fruit juices sold by local street vendors.

scholarly journals Species Diversity of Environmental GIM-1-Producing Bacteria Collected during a Long-Term Outbreak

2016 ◽  
Vol 82 (12) ◽  
pp. 3605-3610 ◽  
Author(s):  
Andreas F. Wendel ◽  
Sofija Ressina ◽  
Susanne Kolbe-Busch ◽  
Klaus Pfeffer ◽  
Colin R. MacKenzie
Keyword(s):  
Resistance Genes ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Resistant Bacteria ◽  
Environmental Sampling ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Content Type

ABSTRACTReports of outbreaks concerning carbapenemase-producing Gram-negative bacteria in which the main source of transmission is the hospital environment are increasing. This study describes the results of environmental sampling in a protracted polyspecies metallo-beta-lactamase GIM-1 outbreak driven by plasmids and bacterial clones ofEnterobacter cloacaeandPseudomonas aeruginosain a tertiary care center. Environmental sampling targeting wet locations (especially sinks) was carried out on a surgical intensive care unit and on a medical ward on several occasions in 2012 and 2013. We were able to demonstrate 43blaGIM-1-carrying bacteria (mainly nonfermenters but alsoEnterobacteriaceae) that were either related or unrelated to clinical strains in 30 sinks and one hair washbasin. GIM-1 was found in 12 different species, some of which are described here as carriers of GIM-1. Forty out of 43 bacteria displayed resistance to carbapenems and, in addition, to various non-beta-lactam antibiotics. Colistin resistance was observed in twoE. cloacaeisolates with MICs above 256 mg/liter. TheblaGIM-1gene was harbored in 12 different class 1 integrons, some without the typical 3′ end. TheblaGIM-1gene was localized on plasmids in five isolates.In vitroplasmid transfer by conjugation was successful in one isolate. The environment, with putatively multispecies biofilms, seems to be an important biological niche for multidrug-resistant bacteria and resistance genes. Biofilms may serve as a “melting pot” for horizontal gene transfer, for dissemination into new species, and as a reservoir to propagate future hospital outbreaks.IMPORTANCEIn Gram-negative bacteria, resistance to the clinically relevant broad-spectrum carbapenem antibiotics is a major public health concern. Major reservoirs for these resistant organisms are not only the gastrointestinal tracts of animals and humans but also the (hospital) environment. Due to the difficulty in eradicating biofilm formation in the latter, a sustained dissemination of multidrug-resistant bacteria from the environment can occur. In addition, horizontal transfer of resistance genes on mobile genetic elements within biofilms adds to the total “resistance gene pool” in the environment. To gain insight into the transmission pathways of a rare and locally restricted carbapenemases resistance gene (blaGIM-1), we analyzed the genetic background of theblaGIM-1gene in environmental bacteria during a long-term polyspecies outbreak in a German hospital.

scholarly journals Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 501 ◽  
Author(s):  
Berthony Deslouches ◽  
Ronald C. Montelaro ◽  
Ken L. Urish ◽  
Yuanpu P. Di
Keyword(s):  
Antimicrobial Peptides ◽  
De Novo ◽  
Multidrug Resistant ◽  
Clinical Development ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Health Crisis ◽  
Test Conditions ◽  
Reduced Activity

The increasing rate of antibiotic resistance constitutes a global health crisis. Antimicrobial peptides (AMPs) have the property to selectively kill bacteria regardless of resistance to traditional antibiotics. However, several challenges (e.g., reduced activity in the presence of serum and lack of efficacy in vivo) to clinical development need to be overcome. In the last two decades, we have addressed many of those challenges by engineering cationic AMPs de novo for optimization under test conditions that typically inhibit the activities of natural AMPs, including systemic efficacy. We reviewed some of the most promising data of the last two decades in the context of the advancement of the field of helical AMPs toward clinical development.

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