scholarly journals A nematode-derived, mitochondrial stress signaling-regulated peptide exhibits broad antibacterial activity

Biology Open ◽  
2021 ◽  
Vol 10 (5) ◽  
Author(s):  
Madhab Sapkota ◽  
Mohammed Adnan Qureshi ◽  
Siraje Arif Mahmud ◽  
Yves Balikosa ◽  
Charlton Nguyen ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Model Organism ◽  
Multidrug Resistant ◽  
Cellular Functions ◽  
Antibiotic Resistant ◽  
Unfolded Protein ◽  
Dramatic Rise ◽  
Protein Response ◽  
Anti Fungal

ABSTRACT A dramatic rise of infections with antibiotic-resistant bacterial pathogens continues to challenge the healthcare field due to the lack of effective treatment regimes. As such, there is an urgent need to develop new antimicrobial agents that can combat these multidrug-resistant superbugs. Mitochondria are central regulators of metabolism and other cellular functions, including the regulation of innate immunity pathways involved in the defense against infection. The mitochondrial unfolded protein response (UPRmt) is a stress-activated pathway that mitigates mitochondrial dysfunction through the regulation of genes that promote recovery of the organelle. In the model organism Caenorhabditis elegans, the UPRmt also mediates an antibacterial defense program that combats pathogen infection, which promotes host survival. We sought to identify and characterize antimicrobial effectors that are regulated during the UPRmt. From our search, we discovered that the antimicrobial peptide CNC-4 is upregulated during this stress response. CNC-4 belongs to the caenacin family of antimicrobial peptides, which are predominantly found in nematodes and are known to have anti-fungal properties. Here, we find that CNC-4 also possesses potent antimicrobial activity against a spectrum of bacterial species and report on its characterization.

scholarly journals OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shira Mandel ◽  
Janna Michaeli ◽  
Noa Nur ◽  
Isabelle Erbetti ◽  
Jonathan Zazoun ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Safety Margin ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Development Of Resistance ◽  
Cecropin A

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.

Isolation and Identification of Multidrug-Resistant Isolates of Uropathogenic Klebsiella spp in Dogs

2021 ◽  
Vol 3 (1) ◽  
pp. 6-12
Author(s):  
M Mustapha ◽  
P Goel
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Urine Samples ◽  
Penicillin G ◽  
Isolation And Identification ◽  
Sensitivity Testing ◽  
Bacterial Organism ◽  
Tract Infections ◽  
Klebsiella Spp

The most widespread ailments in dogs are urinary tract infections (UTIs) caused by bacterial species. It is necessary to recognize the prevailing bacterial pathogens and their susceptibility to antimicrobial agents to effectively treat UTIs. The present study aimed to classify the bacterial organism that causes UTIs in dogs and their patterns of antimicrobial resistance. A total of 141 urine samples were collected from diseased dogs in Veterinary Clinical Complex LUVAS in Hisar, India. Culture, biochemical and sensitivity testing were performed for each of the urine samples based on standard method. Of the total 141 urine samples from dogs, 21 (14.9%) isolates were identified as Klebsiella spp. The isolates were found to be highly resistant to ampicillin (100%), penicillin G (100%), oxytetracycline (100%), enrofloxacin (85.7%), chloramphenicol (80.6%), ceftriaxone (76.2%) and cloxacillin (71.4%), while susceptibility was observed against gentamicin (100%), amikacin (100%) and neomycin (90.5%). In the current study, 19 out of 21 identified isolates were found to be multidrug-resistant. This study indicates that dogs in the study area are found to harbor highly resistant Klebsiella spp. Therefore, when deciding on the antibiotic regimen for UTIs cases, Vets should consider resistance profile of chosen antibacterial agents before usage in order to discourage dissemination of resistant organisms in the study area.

scholarly journals Proteomic Signatures of Clostridium difficile Stressed with Metronidazole, Vancomycin, or Fidaxomicin

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 213 ◽  
Author(s):  
Sandra Maaß ◽  
Andreas Otto ◽  
Dirk Albrecht ◽  
Katharina Riedel ◽  
Anke Trautwein-Schult ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Antibiotic Treatment ◽  
Antimicrobial Agents ◽  
Cell Envelope ◽  
Protein Biosynthesis ◽  
Cellular Functions ◽  
Antibiotic Resistant ◽  
Incidence And Mortality ◽  
A Cell ◽  
Proteomic Response

The anaerobic pathogen Clostridium difficile is of growing significance for the health care system due to its increasing incidence and mortality. As C. difficile infection is both supported and treated by antibiotics, a deeper knowledge on how antimicrobial agents affect the physiology of this important pathogen may help to understand and prevent the development and spreading of antibiotic resistant strains. As the proteomic response of a cell to stress aims at counteracting the harmful effects of this stress, it can be expected that the pattern of a pathogen’s responses to antibiotic treatment will be dependent on the antibiotic mechanism of action. Hence, every antibiotic treatment is expected to result in a specific proteomic signature characterizing its mode of action. In the study presented here, the proteomic response of C. difficile 630∆erm to vancomycin, metronidazole, and fidaxomicin stress was investigated on the level of protein abundance and protein synthesis based on 2D PAGE. The quantification of 425 proteins of C. difficile allowed the deduction of proteomic signatures specific for each drug treatment. Indeed, these proteomic signatures indicate very specific cellular responses to each antibiotic with only little overlap of the responses. Whereas signature proteins for vancomycin stress fulfil various cellular functions, the proteomic signature of metronidazole stress is characterized by alterations of proteins involved in protein biosynthesis and protein degradation as well as in DNA replication, recombination, and repair. In contrast, proteins differentially expressed after fidaxomicin treatment can be assigned to amino acid biosynthesis, transcription, cell motility, and the cell envelope functions. Notably, the data provided by this study hint also at so far unknown antibiotic detoxification mechanisms.

scholarly journals Droplet rather than Aerosol Mediated Dispersion is the Primary Mechanism of Bacterial transmission from Contaminated Hand Washing Sink Traps

2018 ◽  
Author(s):  
Shireen Kotay ◽  
Rodney M. Donlan ◽  
Christine Ganim ◽  
Katie Barry ◽  
Bryan E. Christensen ◽  
...  
Keyword(s):  
Patient Care ◽  
Sampling Methods ◽  
Model Organism ◽  
Air Sampling ◽  
Multidrug Resistant ◽  
Hand Washing ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Potential Reservoir ◽  
Healthcare Associated

ABSTRACTAn alarming rise in hospital outbreaks implicating hand-washing sinks has led to widespread acknowledgement that sinks are a major reservoir of antibiotic resistant pathogens in patient-care areas. An earlier study using a GFP-expressing Escherichia coli (GFP-E. coli) as a model organism demonstrated dispersal from drain biofilm in contaminated sinks. The present study further characterizes the dispersal of microorganisms from contaminated sinks. Replicate hand-washing sinks were inoculated with GFP-E. coli, and dispersion was measured using qualitative (settle plates) and quantitative (air sampling) methods. Dispersal caused by faucet water was captured with settle plates and air sampling methods when bacteria were present on the drain. In contrast, no dispersal was captured without or in between faucet events amending earlier theory that bacteria aerosolize from P-trap and disperse. Numbers of dispersed GFP-E. coli diminished substantially within 30 minutes after faucet usage, suggesting that the organisms were associated with larger droplet-sized particles that are not suspended in the air for long periods.IMPORTANCEAmong the possible environmental reservoirs in a patient care environment, sink drains are increasingly recognized as potential reservoir of multidrug resistant healthcare-associated pathogens to hospitalized patients. With increasing antimicrobial resistance limiting therapeutic options for patients, better understanding of how pathogens disseminate from sink drains is urgently needed. Once this knowledge gap has decreased, interventions can be engineered to decrease or eliminate transmission from hospital sink drains to patients. The current study further defines the mechanisms of transmission for bacteria colonizing sink drains.

scholarly journals Antibiotic Resistant Enterobacteriaceae in Milk Alternatives

Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3070
Author(s):  
Winnie Mukuna ◽  
Abdullah Ibn Mafiz ◽  
Bharat Pokharel ◽  
Aniume Tobenna ◽  
Agnes Kilonzo-Nthenge
Keyword(s):  
Bacterial Species ◽  
Antibiotic Sensitivity ◽  
Enterobacter Cloacae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Limited Data ◽  
Antibiotic Resistant ◽  
Predominant Species ◽  
Diffusion Technique ◽  
Dairy Milk

The consumption of non-dairy milk is on the rise due to health benefits. Although there is increasing inclination towards milk alternatives (MA), there is limited data on antibiotic resistant bacteria in these substitutes. The aim of this study was to investigate antimicrobial resistance of bacteria isolated from MA. A total of 138 extracts from almonds (n = 63), cashew nuts (n = 36), and soybeans (n = 39) were analyzed for Enterobacteriaceae. The identification of the bacteria was based on biochemical and PCR methods. Antibiotic sensitivity was determined by using the Kirby-Bauer disk diffusion technique. Overall, 31% (43 of 138) of extracts were positive for Enterobacteriaceae. Ten bacterial species were identified, of which Enterobacter cloacae (42.7%) and Enterobacter cancerogenus (35.4%) were the most predominant species (p < 0.05). Antibiotic resistance was exhibited to vancomycin (88.3%), novobiocin (83.8%), erythromycin (81.1%), which was significantly higher (p < 0.05) than in tetracycline (59.5%), cefpodoxime (30.6%), and nalidixic acid (6.3%). There was no resistance displayed to kanamycin and imipenem. ERY-NOV-VAN-TET and ERY-NOV-CEP-VAN-TET were the most common resistant patterns displayed by Enterobacter cloacae. The findings of this study suggest that MAs, though considered healthy, may be a reservoir of multidrug resistant opportunist pathogens.

scholarly journals Strain diversity and antibiotic-sensitivity of staphylococcus spp. Isolates from patients of multiprofile pediatric hospital in St. Petersburg, Russia

2021 ◽  
Vol 12 (4) ◽  
pp. 15-25
Author(s):  
D. P. Gladin ◽  
A. R. Khairullina ◽  
A. M. Korolyuk ◽  
N. S. Kozlova ◽  
O. V. Ananyeva ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Antibiotic Sensitivity ◽  
Specific Weight ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Therapeutic Effects ◽  
Antimicrobial Drugs ◽  
Antibiotic Resistant ◽  
Resistant Strains ◽  
Staphylococcus Spp

Background. Staphylocci are the leading pus-forming Gram-positive bacteria in the childrens hospitals. The prevalence of the antibiotic resistant strains among them limits therapeutic effects of infections in children. Aim. The research is aimed at characterizing the species of staphylococcus, which are isolated from the different clinical specimens of the patients at the clinics of Saint Petersburg State Pediatric Medical University in 2019, and analysis of their susceptibility to antimicrobial agents. Materials and metods. According to the clinical recommendations of 2018, susceptibility to antimicrobial drugs (AMD) was revealed in 860 strains of staphylococci determined by the disc diffusion method, which were identified by the automated analyser Vitek-2 compact. Results. Six species of staphylococci were represented at the hospital departments, among which Staphylococcus epidermidis prevailed in the departments of the neonate pathology department and intensive care units (63.0% and 46.2% respectively), Staphylococcus aureus is commonly found at the departments of surgery and the departments of the therapeutic profiles (61.7% and 46.2% respectively). More than a half of the staphylococci strains (63.0%) were resistant to at least one of the antimicrobial drugs. Vancomycin and line solid showed the highest activity to these staphylococci. High specific weight of multidrug resistant (MDR) bacteria (37.8%) and extensively drug resistant (XDR) strains of the phenotype (33.0%) was revealed. The level of antibiotic resistant strains was the highest in Staphylococcus haemolyticus (98.1%) and S. epidermidis (82.0%), while the specific weight of the resistant ones, MDR and XDR strains was extremely low among S. aureus (16.2%, 1.5% and 0.4 respectively), as well as in methicillin-resistant isolates (0.8%). Conclusions. A great variety of antibiotic resistance was revealed among the staphylococci. The prevalence of these strains in the pediatric hospitals requires constant local monitoring of the antibiotic resistant staphylococci.

scholarly journals A Study of Isolation and Identification of Multidrug Resistant Pseudomonas aeruginosa from Wound Specimen

2020 ◽  
pp. 26-31
Author(s):  
Maria Muddassir ◽  
Sadaf Munir ◽  
Almas Raza ◽  
Adeel Iqbal ◽  
Muddassir Ahmed ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Antimicrobial Agents ◽  
Morphological Characteristics ◽  
Multidrug Resistant ◽  
Hospitalized Patients ◽  
Clinical Samples ◽  
Isolation And Identification ◽  
Antimicrobial Drugs ◽  
Antibiotic Resistant

Background: Pseudomonas aeruginosa is a clinically important pathogenic microbe in hospitalized patients. It is a major cause of mortality and morbidity having a number of mechanisms that make it antibiotic resistant. Considering the dearth of antimicrobial drugs to treat infection with this pathogen, it has become a necessity to open up new arena for treatment with this organism. Recently, there has been an up rise in the number of multidrug resistant pathogenic strains of Pseudomonas aeruginosa. Objective: Isolation and identification of multidrug resistant Pseudomonas aeruginosa from wound specimens and to evaluate the antibiotic resistant strains of this microbe. Methodology: One hundred and fifty clinical samples of wound were taken from hospitalized patients at Jinnah hospital Lahore during the period of October 2019 to April 2020. In total, twenty (20) isolates of Pseudomonas aeruginosa were identified using the cultural features, morphological characteristics and various biochemical tests plus the Vitek 2 system. Blue/green, brown /blue and yellow/green pigment production showed the presence and growth of Pseudomonas aeruginosa. Results: Percentage of Pseudomonas aeruginosa in females came out to be 15% as compared to 11.42% in males. This was followed by testing susceptibility of isolates of Pseudomonas aeruginosa to various antimicrobial drugs. Piperacillin/tazobactam and meropenem showed the highest efficacy against Pseudomonas aeruginosa. Highest resistance was exhibited against trimethoprim/sulfamethoxazole which was 75%. Conclusion: Most isolates showed multidrug resistance to four or more drugs. Development of multidrug resistance has emerged as a global problem with pathogens commonly causing infections becoming increasingly resistant to antimicrobial agents.

scholarly journals The Neutrally Charged Diarylurea Compound PQ401 Kills Antibiotic-Resistant and Antibiotic-Tolerant Staphylococcus aureus

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Wooseong Kim ◽  
Guijin Zou ◽  
Wen Pan ◽  
Nico Fricke ◽  
Hammad A. Faizi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Lipid Bilayers ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Lead Compound ◽  
Neutral Form ◽  
Cationic Form ◽  
Antibiotic Resistant ◽  
Content Type

ABSTRACT Resistance or tolerance to traditional antibiotics is a challenging issue in antimicrobial chemotherapy. Moreover, traditional bactericidal antibiotics kill only actively growing bacterial cells, whereas nongrowing metabolically inactive cells are tolerant to and therefore “persist” in the presence of legacy antibiotics. Here, we report that the diarylurea derivative PQ401, previously characterized as an inhibitor of the insulin-like growth factor I receptor, kills both antibiotic-resistant and nongrowing antibiotic-tolerant methicillin-resistant Staphylococcus aureus (MRSA) by lipid bilayer disruption. PQ401 showed several beneficial properties as an antimicrobial lead compound, including rapid killing kinetics, low probability for resistance development, high selectivity to bacterial membranes compared to mammalian membranes, and synergism with gentamicin. In contrast to well-studied membrane-disrupting cationic antimicrobial low-molecular-weight compounds and peptides, molecular dynamic simulations supported by efficacy data demonstrate that the neutral form of PQ401 penetrates and subsequently embeds into bacterial lipid bilayers more effectively than the cationic form. Lastly, PQ401 showed efficacy in both the Caenorhabditis elegans and Galleria mellonella models of MRSA infection. These data suggest that PQ401 may be a lead candidate for repurposing as a membrane-active antimicrobial and has potential for further development as a human antibacterial therapeutic for difficult-to-treat infections caused by both drug-resistant and -tolerant S. aureus. IMPORTANCE Membrane-damaging antimicrobial agents have great potential to treat multidrug-resistant or multidrug-tolerant bacteria against which conventional antibiotics are not effective. However, their therapeutic applications are often hampered due to their low selectivity to bacterial over mammalian membranes or their potential for cross-resistance to a broad spectrum of cationic membrane-active antimicrobial agents. We discovered that the diarylurea derivative compound PQ401 has antimicrobial potency against multidrug-resistant and multidrug-tolerant Staphylococcus aureus. PQ401 selectively disrupts bacterial membrane lipid bilayers in comparison to mammalian membranes. Unlike cationic membrane-active antimicrobials, the neutral form of PQ401 rather than its cationic form exhibits maximum membrane activity. Overall, our results demonstrate that PQ401 could be a promising lead compound that overcomes the current limitations of membrane selectivity and cross-resistance. Also, this work provides deeper insight into the design and development of new noncharged membrane-targeting therapeutics to combat hard-to-cure bacterial infections.

scholarly journals Design, Overproduction and Purification of the Chimeric Phage Lysin MLTphg Fighting against Staphylococcus aureus

Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1587
Author(s):  
Feng Wang ◽  
Xiaohang Liu ◽  
Zhengyu Deng ◽  
Yao Zhang ◽  
Xinyu Ji ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Conventional Antibiotics ◽  
Phage Lysin ◽  
Shed Light

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.

scholarly journals Clinical Significance of Manuka and Medical-Grade Honey for Antibiotic-Resistant Infections: A Systematic Review

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 766
Author(s):  
Victoria C. Nolan ◽  
James Harrison ◽  
John E. E. Wright ◽  
Jonathan A. G. Cox
Keyword(s):  
Systematic Review ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Original Research ◽  
Burn Treatment ◽  
Antibiotic Resistant ◽  
Global Issue ◽  
Antibiotic Discovery ◽  
Medical Grade

Antimicrobial resistance is an ever-increasing global issue that has the potential to overtake cancer as the leading cause of death worldwide by 2050. With the passing of the “golden age” of antibiotic discovery, identifying alternative treatments to commonly used antimicrobials is more important than ever. Honey has been used as a topical wound treatment for millennia and more recently has been formulated into a series of medical-grade honeys for use primarily for wound and burn treatment. In this systematic review, we examined the effectiveness of differing honeys as an antimicrobial treatment against a variety of multidrug-resistant (MDR) bacterial species. We analysed 16 original research articles that included a total of 18 different types of honey against 32 different bacterial species, including numerous MDR strains. We identified that Surgihoney was the most effective honey, displaying minimum inhibitory concentrations as low as 0.1% (w/v); however, all honeys reviewed showed a high efficacy against most bacterial species analysed. Importantly, the MDR status of each bacterial strain had no impact on the susceptibility of the organism to honey. Hence, the use of honey as an antimicrobial therapy should be considered as an alternative approach for the treatment of antibiotic-resistant infections.

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