scholarly journals Synergy pattern of short cationic antimicrobial peptides against multidrug-resistant Pseudomonas aeruginosa

2019 ◽  
Author(s):  
Serge Ruden ◽  
Annika Rieder ◽  
Thomas Schwartz ◽  
Ralf Mikut ◽  
Kai Hilpert
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Peptides ◽  
Pathogenic Bacteria ◽  
Synergistic Effects ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Multi Drug Resistance ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Conventional Antibiotics

AbstractWith the rise of various multi-drug resistance pathogenic bacteria, worldwide health care is under pressure to respond. Conventional antibiotics are failing and the development of novel classes or alternative strategies is a major priority. Antimicrobial peptides (AMPs) can not only kill multi-drug resistant bacteria, but also can be used synergistically with conventional antibiotics. We selected 30 short AMPs from different origins and measured their synergy in combination with Polymyxin B, Piperacillin, Ceftazidime, Cefepime, Meropenem, Imipenem, Tetracycline, Erythromycin, Kanamycin, Tobramycin, Amikacin, Gentamycin, and Ciprofloxacin. In total 403 unique combinations were tested against a multi-drug resistant Pseudomonas aeruginosa isolate (PA910). As a measure of the synergistic effects, fractional inhibitory concentrations (FICs) were determined using microdilution assays with FICs ranges between 0.25 and 2. A high number of combinations between peptides and Polymyxin B, Erythromycin and Tetracycline were found to be synergistic. Novel variants of Indolicidin also showed a high frequency in synergist interaction.

A quest to the therapeutic arsenal: Novel strategies to combat multidrug-resistant bacteria

2021 ◽  
Vol 21 ◽  
Author(s):  
Priyanka Ashwath ◽  
Akhila Dharnappa Sannejal
Keyword(s):  
Multidrug Resistant ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antimicrobial Drugs ◽  
Short Palindromic Repeat ◽  
Prevention Of Infections ◽  
Resistant Bacterial Strain ◽  
Conventional Antibiotics ◽  
Drug Resistant Strains

: The increasing resistance of the disease-causing pathogens to antimicrobial drugs is a public health concern and a socio-economic burden. The emergence of multi-drug resistant strains has made it harder to treat and combat infectious diseases with available conventional antibiotics. There are currently few effective therapeutic regimens for the successful prevention of infections caused by drug-resistant microbes. The various alternative strategies used in the recent past to decrease and limit antibiotic resistance in pathogens include bacteriophages, vaccines, anti-biofilm peptides, and antimicrobial peptides. However, in this review, we focus on the novel and robust molecular approach of antisense RNA (asRNA) technology and the clustered regulatory interspaced short palindromic repeat (CRISPR)-based antibiotic therapy, which can be exploited to selectively eradicate the drug-resistant bacterial strain in a sequence-specific fashion establishing opportunities in the treatment of multi-drug resistant related infections.

scholarly journals Evolution under low antibiotic concentrations: a risk for the selection of Pseudomonas aeruginosa multidrug resistant mutants in nature

2021 ◽  
Author(s):  
Fernando Sanz-García ◽  
Sara Hernando-Amado ◽  
José Luis Martínez
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Published Data ◽  
Natural Ecosystems ◽  
Clinical Value ◽  
Drug Concentrations ◽  
Resistant Mutants

ABSTRACTBACKGROUNDAntibiotic pollution of non-clinical environments might have a relevant impact on human health if resistant pathogens are selected. However, this potential risk is often overlooked, since drug concentrations in nature are usually below their minimal inhibitory concentrations (MICs). Albeit, antibiotic resistant bacteria can be selected even at sub-MIC concentrations, in a range that is dubbed the sub-MIC selective window, which depends on both the antibiotic and the pathogen.OBJECTIVESDetermine the sub-MIC selective windows of seven antibiotics of clinical relevance in the opportunistic pathogen Pseudomonas aeruginosa and evaluate the risk for selecting resistant mutants in nature, based on published data about the amount of antimicrobials detected in natural environments.METHODSWe conducted evolution experiments of P. aeruginosa PA14 in presence of sub-MIC concentrations of ceftazidime, amikacin, levofloxacin, ciprofloxacin, tetracycline, polymyxin B or imipenem, and measured drug susceptibility of the evolved populations.RESULTSSub-MIC selective window of quinolones was the largest, and the ones of polymyxin B and imipenem, the narrowest. Clinically relevant multidrug resistant (MDR) mutants (presenting MICs above EUCAST clinical breakpoints) arose within the sub-MIC selective windows of the majority of antibiotics tested, being these phenotypes probably mediated by efflux pumps′ activity.DISCUSSIONOur data show that the concentration of antibiotics reported in aquatic ecosystems -colonizable by P. aeruginosa- are, in occasions, higher than the ones able to select MDR mutants. This finding has implications for understanding the role of different ecosystems and conditions in the emergence of antibiotic resistance from a One-Health point of view. Further, it highlights the importance of delineating the sub-MIC selective windows for drugs of clinical value in pathogens with environmental niches, in order to evaluate the health risks due to antibiotic pollution of natural ecosystems and ultimately tackle antibiotic resistance.

scholarly journals The Concerted Action of Two B3-Like Prophage Genes Excludes Superinfecting Bacteriophages by Blocking DNA Entry into Pseudomonas aeruginosa

2020 ◽  
Vol 94 (15) ◽  
Author(s):  
Marco Antonio Carballo-Ontiveros ◽  
Adrián Cazares ◽  
Pablo Vinuesa ◽  
Luis Kameyama ◽  
Gabriel Guarneros
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Alternative Therapy ◽  
Multidrug Resistant ◽  
Open Reading Frames ◽  
Resistant Bacteria ◽  
Content Type ◽  
Secondary Infections ◽  
Genes Encoding

ABSTRACT In this study, we describe seven vegetative phage genomes homologous to the historic phage B3 that infect Pseudomonas aeruginosa. Like other phage groups, the B3-like group contains conserved (core) and variable (accessory) open reading frames (ORFs) grouped at fixed regions in their genomes; however, in either case, many ORFs remain without assigned functions. We constructed lysogens of the seven B3-like phages in strain Ps33 of P. aeruginosa, a novel clinical isolate, and assayed the exclusion phenotype against a variety of temperate and virulent superinfecting phages. In addition to the classic exclusion conferred by the phage immunity repressor, the phenotype observed in B3-like lysogens suggested the presence of other exclusion genes. We set out to identify the genes responsible for this exclusion phenotype. Phage Ps56 was chosen as the study subject since it excluded numerous temperate and virulent phages. Restriction of the Ps56 genome, cloning of several fragments, and resection of the fragments that retained the exclusion phenotype allowed us to identify two core ORFs, so far without any assigned function, as responsible for a type of exclusion. Neither gene expressed separately from plasmids showed activity, but the concurrent expression of both ORFs is needed for exclusion. Our data suggest that phage adsorption occurs but that phage genome translocation to the host’s cytoplasm is defective. To our knowledge, this is the first report on this type of exclusion mediated by a prophage in P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa is a Gram-negative bacterium frequently isolated from infected immunocompromised patients, and the strains are resistant to a broad spectrum of antibiotics. Recently, the use of phages has been proposed as an alternative therapy against multidrug-resistant bacteria. However, this approach may present various hurdles. This work addresses the problem that pathogenic bacteria may be lysogenized by phages carrying genes encoding resistance against secondary infections, such as those used in phage therapy. Discovering phage genes that exclude superinfecting phages not only assigns novel functions to orphan genes in databases but also provides insight into selection of the proper phages for use in phage therapy.

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.

scholarly journals In vivo emergence of resistance to cefiderocol in an XDR Pseudomonas aeruginosa and an MDR Citrobacter koseri after prolonged therapy: a case report.

2020 ◽  
Author(s):  
Carolina Grande Perez ◽  
Evelyne Maillart ◽  
Véronique Yvette Miendje Deyi ◽  
Te Din Daniel Huang ◽  
Prochore Kamgang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Class A ◽  
Stewardship Program ◽  
Class D ◽  
Emergence Of Resistance

Abstract The non-fermenters, e.g. Pseudomonas aeruginosa, and the extended spectrum β-lactamases or carbapenemases producing enterobacteriaceae represent a serious threat for patients admitted in Intensive Care Units (ICUs). News antibiotics have been developed to treat multidrug resistant bacteria. However, treatment emerging resistance has been shown for many of these newest antibiotics. Cefiderocol, a siderophore-antibiotic, has been developed to overcome most of the resistance mechanisms and shows great efficacy against most multi-drug resistant and extensively drug resistant Gram-negative bacteria, including the non-fermenters. We report the case of a patient abundantly treated with antibiotics. He received 158 days of antibiotherapy on 230 hospitalization days, including a six-week course of cefiderocol, in 14 different treatment lines. The patient developed a Pseudomonas aeruginosa (MIC: 8 µg/ml, GES type ESBL) and a Citrobacter koseri (MIC: 16 µg/ml, CTX-M group 9 type class A β-lactamase and a class D OXA-1 oxacillinase) resistant to cefiderocol. This antibiotic should be used with caution to preserve its efficacy, within a strict antimicrobial stewardship program.

scholarly journals Analysis of Susceptibility Patterns of Pseudomonas aeruginosa and Isolation, Characterization of Lytic Bacteriophages Targeting Multi Drug Resistant Pseudomonas aeruginosa

2018 ◽  
Vol 11 (2) ◽  
pp. 1105-1117 ◽  
Author(s):  
Shri Natrajan Arumugam ◽  
Akarsh Chickamagalur Rudraradhya ◽  
Sathish Sadagopan ◽  
Sunilkumar Sukumaran ◽  
Ganesh Sambasivam ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Host Range ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Dilution Method ◽  
Drug Resistant ◽  
Susceptibility Pattern ◽  
Infectivity Rate

Pseudomonas aeruginosa is known to be a major cause of Hospital Acquired Infections leading to high mortality in immune-compromised patients. Due to precipitous rise in antibiotic resistance, bacteriophages are significant alternative therapeutic approach for treatment and to combat resistance development. Objective of the current study was to identify MDR Pseudomonas aeruginosa from clinical isolates and to isolate bacteriophages from sewage samples against these MDR Pseudomonas aeruginosa strains. One hundred and forty-four Pseudomonas isolates were tested for their susceptibility pattern with 13 different antibiotics by micro-broth dilution method. Frequency of multidrug resistant (MDR) and Extensive Drug resistant (XDR) of Pseudomonas aeruginosa were found to be 35.5% and 23.6%, respectively. 7.61% isolates were identified as Pan drug resistant (PDR). Rate of susceptibility pattern were Piperacillin/Tazobactam 75%, Polymyxin B 74.6%, Meropenem 73.6%, Colistin 69.2%, Cefepime 54.9%, Ciprofloxacin 54.2%, Gentamicin 54.2%, Aztreonam 53.5%, Tobramycin 47.9%, Ticarcillin/Clavulanic acid 46.9%, Ertapenem 45.8%, Ceftazidime 40.3% and Imipenem 39.2%. Ninety-four bacteriophages were isolated from sewage samples against Pseudomonas aeruginosa PAO1/ATCC9027/clinical strains and host range testing study was carried out with all MDR clinical isolates. Among 51 MDR strains 34 strains were infected by phages. Phage infectivity rate were calculated for individual phages based on their host range infectivity results. AP025 and AP006 phages exhibited good infectivity rate of 39% and 30% respectively against MDR strains. Combination of 5 phages (AP002, AP006, AP011, AP025 and AP067) lysed 62.7% of the strains. Based on the obtained results, phages could be employed for treatment of infections caused by MDR strains with substantiated in-vivo experiments.

scholarly journals Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244673
Author(s):  
Julalak C. Ontong ◽  
Nwabor F. Ozioma ◽  
Supayang P. Voravuthikunchai ◽  
Sarunyou Chusri
Keyword(s):  
Antibacterial Activity ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibacterial Effects ◽  
Drug Resistant Bacteria ◽  
Multidrug Resistant Pathogens ◽  
Conventional Antibiotics ◽  
Global Health Problem

Multidrug resistant Enterobacterales have become a serious global health problem, with extended hospital stay and increased mortality. Antibiotic monotherapy has been reported ineffective against most drug resistant bacteria including Klebsiella pneumoniae, thus encouraging the use of multidrug therapies as an alternative antibacterial strategy. The present works assessed the antibacterial activity of colistin against K. pneumoniae isolates. Resistant isolates were tested against 16 conventional antibiotics alone and in combination with colistin. The results revealed that all colistin resistant isolates demonstrated multidrug resistance against the tested antibiotics except amikacin. At sub-inhibitory concentrations, combinations of colistin with amikacin, or fosfomycin showed synergism against 72.72% (8 of 11 isolates). Colistin with either of gentamicin, meropenem, cefoperazone, cefotaxime, ceftazidime, moxifloxacin, minocycline, or piperacillin exhibited synergism against 81.82% (9 of 11 isolates). Combinations of colistin with either of tobramycin or ciprofloxacin showed synergism against 45.45% (5 in 11 isolates), while combinations of colistin with imipenem or ceftolozane and tazobactam displayed 36.36% (4 of 11 isolates) and 63.64% (7 of 11 isolates) synergism. In addition, combinations of colistin with levofloxacin was synergistic against 90.91% (10 of 11 isolates). The results revealed that combinations of colistin with other antibiotics could effectively inhibit colistin resistant isolates of K. pneumoniae, and thus could be further explore for the treatment of multidrug resistant pathogens.

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.

Antimicrobial peptides isolated from the blood of farm animals

2010 ◽  
Vol 50 (7) ◽  
pp. 660 ◽  
Author(s):  
Pak-Lam Yu ◽  
Danitsja S. van der Linden ◽  
Haryadi Sugiarto ◽  
Rachel C. Anderson
Keyword(s):  
Antimicrobial Peptides ◽  
Pathogenic Bacteria ◽  
Synergistic Effects ◽  
Waste Product ◽  
Pharmaceutical Products ◽  
Farm Animals ◽  
Antimicrobial Substances ◽  
Spectrum Activity ◽  
Conventional Antibiotics

The development of antimicrobial resistance by pathogenic bacteria has fuelled the search for alternatives to conventional antibiotics. Endogenous antimicrobial peptides have the potential to be used as new antimicrobial substances because they have low minimum inhibitory concentration in vitro, have broad-spectrum activity, neutralise lipopolysaccharides, promote wound healing and have synergistic effects with conventional antibiotics. Farm animals, in particular the blood that is a by-product of the meat and poultry industries, are an abundant, and currently underutilised, source of such antimicrobial peptides. These antimicrobial peptides could be isolated and developed into high-value products such as biopreservatives, topical neutraceutical products and pharmaceuticals. There have been some clinical trials of antimicrobial peptides as pharmaceutical products, but up to now, the trials have shown disappointing results. Further research and development is still needed before such peptides can be commercialised and full advantage taken of this waste product of the meat and poultry industries.

scholarly journals A Mig-14-like protein (PA5003) affects antimicrobial peptide recognition in Pseudomonas aeruginosa

Microbiology ◽  
2011 ◽  
Vol 157 (9) ◽  
pp. 2647-2657 ◽  
Author(s):  
Nicholas Jochumsen ◽  
Yang Liu ◽  
Søren Molin ◽  
Anders Folkesson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Fluorescent Protein ◽  
Flow Chamber ◽  
Gene Encoding ◽  
Conventional Antibiotics ◽  
Green Fluorescent

The evolution of antibiotic resistance in pathogenic bacteria is a growing global health problem which is gradually making the treatment of infectious diseases less efficient. Antimicrobial peptides are small charged molecules found in organisms from the complete phylogenetic spectrum. The peptides are attractive candidates for novel drug development due to their activity against bacteria that are resistant to conventional antibiotics, and reports of peptide resistance are rare in the clinical setting. Paradoxically, many clinically relevant bacteria have mechanisms that can recognize and respond to the presence of cationic antimicrobial peptides (CAMPs) in the environment by changing the properties of the microbial surface thereby increasing the tolerance of the microbes towards the peptides. In Pseudomonas aeruginosa an essential component of this inducible tolerance mechanism is the lipopolysaccharide modification operon arnBCADTEF–PA3559 which encodes enzymes required for LPS alterations leading to increased antimicrobial peptide tolerance. The expression of the operon is induced by the presence of CAMPs in the environment but the molecular mechanisms underlying the cellular recognition of the peptides are poorly elucidated. In this work, we investigate the factors influencing arnB expression by transposon mutagenesis and arnB promoter green fluorescent protein reporters. We have identified a novel gene encoding a Mig-14-like protein that is required for recognition of the CAMPs colistin and Novispirin G10 by P. aeruginosa. Moreover, we show that this gene is also required for the formation of CAMP-tolerant subpopulations in P. aeruginosa hydrodynamic flow chamber biofilms.

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