scholarly journals In vitro activity of antimicrobial peptide CDP-B11 alone and in combination with colistin against colistin-resistant and multidrug-resistant Escherichia coli

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaitlin S. Witherell ◽  
Jason Price ◽  
Ashok D. Bandaranayake ◽  
James Olson ◽  
Douglas R. Call

AbstractMultidrug-resistant bacteria are a growing global concern, and with increasingly prevalent resistance to last line antibiotics such as colistin, it is imperative that alternative treatment options are identified. Herein we investigated the mechanism of action of a novel antimicrobial peptide (CDP-B11) and its effectiveness against multidrug-resistant bacteria including Escherichia coli #0346, which harbors multiple antibiotic-resistance genes, including mobilized colistin resistance gene (mcr-1). Bacterial membrane potential and membrane integrity assays, measured by flow cytometry, were used to test membrane disruption. Bacterial growth inhibition assays and time to kill assays measured the effectiveness of CDP-B11 alone and in combination with colistin against E. coli #0346 and other bacteria. Hemolysis assays were used to quantify the hemolytic effects of CDP-B11 alone and in combination with colistin. Findings show CDP-B11 disrupts the outer membrane of E. coli #0346. CDP-B11 with colistin inhibits the growth of E. coli #0346 at ≥ 10× lower colistin concentrations compared to colistin alone in Mueller–Hinton media and M9 media. Growth is significantly inhibited in other clinically relevant strains, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In rich media and minimal media, the drug combination kills bacteria at a lower colistin concentration (1.25 μg/mL) compared to colistin alone (2.5 μg/mL). In minimal media, the combination is bactericidal with killing accelerated by up to 2 h compared to colistin alone. Importantly, no significant red blood hemolysis is evident for CDP-B11 alone or in combination with colistin. The characteristics of CDP-B11 presented here indicate that it can be used as a potential monotherapy or as combination therapy with colistin for the treatment of multidrug-resistant infections, including colistin-resistant infections.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S285-S285
Author(s):  
Hyeri Seok ◽  
Ji Hoon Jeon ◽  
Hee Kyoung Choi ◽  
Won Suk Choi ◽  
Dae Won Park ◽  
...  

Abstract Background Fosfomycin is one of the antibiotics that may be a candidate for the next-generation antimicrobial agents againt multidrug-resistant bacteria. To date, it is known that the resistance rate is not high for Escherichia coli. However, it is necessary to update the fosfomycin resistance rates in E. coli according to the studies that extended spectrum β-lactamase (ESBL) producing E. coli strains are highly resistance to fosfomycin. We evaluated the resistance rate of fosfomycin, the resistant mechanism of fosfomycin in E. coli, and the activity of fosfomycin against susceptible and resistant strains of E. coli. Methods A total of 283 clinical isolates was collected from patients with Escherichia coli species during the period of January 2018 to June 2018, in three tertiary hospitals of Republic of Korea. In vitro antimicrobial susceptibility tests were performed in all E. coli isolates using the broth microdilution method according to the Clinical and Laboratory Standard Institute (CLSI). Multilocus sequence typing (MLST) of the Oxford scheme was conducted to determine the genotypes of E. coli isolated. Fosfomycin genes were investigated for all fosfomycin-resistant E. coli strains. Results The overall resistance rate to fosfomycin was 10.2%, compared with 53.4%, 46.3%, 41.3%, 31.1%, 10.6%, 2.5%, and 2.1% for ciprofloxacin, cefixime, cefepime, piperacillin/tazobactam, colistin, ertapenem, and amikacin, respectively. The 29 fosfomycin-resistant isolates did not show a clonal pattern on the phylogenetic tree. MurA and glp genes were identified in all strains. FosA3 were identified in two strains and uhp gene were identified in 4 strains. In time-kill curve studies, fosfomycin was more bactericidal than cefixime against all sensitive E. coli strain. Morever, fosfomycin was more bactericidal than piperacillin/tazobactam against ESBL-producing E. coli strain. Conclusion The resistant rate of fosfomycin to E. coli is still low. Fosfomycin was active against E. coli including ESBL producing strains. Disclosures All authors: No reported disclosures.


2019 ◽  
Vol 61 (1) ◽  
Author(s):  
Edgarthe Priscilla Ngaiganam ◽  
Isabelle Pagnier ◽  
Wafaa Chaalal ◽  
Thongpan Leangapichart ◽  
Selma Chabou ◽  
...  

Abstract Background We investigate here the presence of multidrug-resistant bacteria isolated from stool samples of yellow-legged gulls and chickens (n = 136) in urban parks and beaches of Marseille, France. Bacterial isolation was performed on selective media, including MacConkey agar with ceftriaxone and LBJMR medium. Antibiotic resistance genes, including extended-spectrum β-lactamases (ESBL) (i.e. blaCTX-M, blaTEM and blaSHV), carbapenemases (blaKPC, blaVIM, blaNDM, blaOXA-23, blaOXA-24, blaOXA-48 and blaOXA-58) and colistin resistance genes (mcr-1 to mcr-5) were screened by real-time PCR and standard PCR and sequenced when found. Results Of the 136 stools samples collected, seven ESBL-producing Gram-negative bacteria (BGN) and 12 colistin-resistant Enterobacteriaceae were isolated. Among them, five ESBL-producing Escherichia coli and eight colistin-resistant Hafnia alvei strains were identified. Four blaTEM-1 genes were detected in yellow-legged gulls and chickens. Three CTX-M-15 genes were detected in yellow-legged gulls and pigeons, and one CTX-M-1 in a yellow-legged gull. No mcr-1 to mcr-5 gene were detected in colistin-resistant isolates. Genotyping of E. coli strains revealed four different sequence types already described in humans and animals and one new sequence type. Conclusions Urban birds, which are believed to have no contact with antibiotics appear as potential source of ESBL genes. Our findings highlight the important role of urban birds in the proliferation of multidrug-resistant bacteria and also the possible zoonotic transmission of such bacteria from wild birds to humans.


2017 ◽  
Vol 66 (4) ◽  
pp. 533-536 ◽  
Author(s):  
Moreno Bondi ◽  
Anna Mazzini ◽  
Simona de Niederhäusern ◽  
Ramona Iseppi ◽  
Patrizia Messi

The authors studied the in vitro antibacterial activity of the photo-activated porphyrin meso-tri(N-methyl-pyridyl), mono(N-tetradecyl-pyridyl)porphine (C14) against four multidrug-resistant bacteria: Staphylococcus aureus, Enterococcus faecalis (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative). Using 10 μg/ml of porphyrin and 60 sec irradiation we observed the remarkable susceptibility of S. aureus and E. faecalis to treatment while, under the same conditions, E. coli and P. aeruginosa showed very low susceptibility. In a later stage, suspensions of Gram-negative bacteria were processed with EDTA before photo-activation, obtaining a significant decrease in viable counts. In view of the results, if the combination of low porphyrin concentrations and short irradiation times will be effective in vivo also, this approach could be a possible alternative to antibiotics, in particular against localized infections due to multidrug-resistant microorganisms.


2012 ◽  
Vol 56 (6) ◽  
pp. 3318-3323 ◽  
Author(s):  
Kairong Wang ◽  
Jiexi Yan ◽  
Ru Chen ◽  
Wen Dang ◽  
Bangzhi Zhang ◽  
...  

ABSTRACTThe extensive use of antibiotics in medicine, the food industry, and agriculture has resulted in the frequent emergence of multidrug-resistant bacteria, which creates an urgent need for new antibiotics. It is now widely recognized that antimicrobial peptides (AMPs) could play a promising role in fighting multidrug-resistant bacteria. Antimicrobial peptide polybia-CP was purified from the venom of the social waspPolybia paulista. In this study, we synthesized polybia-CP and studied its action mode of antibacterial activity. Our results revealed that polybia-CP has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. The results from both the real bacterial membrane and thein vitromodel membrane showed that polybia-CP is membrane active and that its action target is the membrane of bacteria. It is difficult for bacteria to develop resistance to polybia-CP, which may thus offer a new strategy for defending against resistant bacteria in medicine and the food and farming industries.


Author(s):  
Daile Meek Salvador-Membreve ◽  
Windell L. Rivera

Abstract Lakes are one of the sinks of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs); however, information on ARB and ARGs in lakes in the Philippines is scarce. In this study, Escherichia coli was isolated from the largest freshwater lake in the Philippines, Laguna Lake, to detect antibiotic resistance and the presence of ARGs. Broth microdilution assay (BMA) and molecular identification of five environmentally prevalent ARGs (strA, blaCTX-M, blaSHV, blaTEM, and tetA) were performed. The majority (75.70%) of the isolates harbored at least one of the targeted antibiotic genes. Multiplex PCR detected about 49.07% of the isolates had genes for extended-spectrum β-lactamases (ESBL), which were mostly represented by blaTEM (47.66%). The genes strA and tetA were observed in this study with detection frequencies of 29.91 and 45.33%, respectively. About 95.69% of thermotolerant E. coli isolates were non-susceptible to six different antibiotics using BMA. Nearly 37% of the isolates were found to be multidrug-resistant (MDR) with most isolates resistant to ampicillin (81.72%). Furthermore, the occurrence of ESBL genes was significantly correlated with tetA genes (P = 0.013). To date, this study is the first to report on the presence of MDR and thermotolerant E. coli in Laguna Lake, Philippines.


2020 ◽  
Author(s):  
Franziska Jäger ◽  
Anaïs Lamy ◽  
Nina Guerini ◽  
Wei-Sheng Sun ◽  
Ronnie P-A Berntsson

AbstractMultidrug resistant bacteria are one of the most important current threats to public health and a serious problem in hospital acquired infections (HAIs). Most antibiotic resistance genes are acquired via conjugative gene transfer, in a process that is mediated by a protein machinery called the Type 4 Secretion System (T4SS). The core of the T4SS is a multiprotein complex that spans both the cell wall and cellular membrane(s), serving as a channel for macromolecular secretion. Although the majority of multidrug resistant bacteria responsible for HAIs are of Gram-positive origin, with Enterococci being major contributors, mostly Gram-negative T4SSs have been characterized. Here we describe the structure and organisation of PrgL, one of the seven membrane proteins forming the translocation channel of the T4SS encoded by the pCF10 plasmid from Enterococcus faecalis. We present the structure of the C-terminal domain of PrgL, which displays similarity to VirB8 proteins of Gram-negative secretion systems. PrgL forms dimers and higher order oligomers but does not interact strongly with the other T4SS components. In vitro experiments show that the soluble domain alone is enough to drive both dimerization and dodecamerisation, with a dimerization interface that differs from all other known VirB8-like proteins. Our findings provide insight into the molecular building blocks of Gram-positive T4SS, highlighting similarities but also unique features in PrgL compared to other VirB8-like proteins.


2019 ◽  
Vol 7 (2) ◽  
pp. 181-183
Author(s):  
Diep Le Ngoc ◽  
Ly Nguyen Thi Vu ◽  
Tro Chau Van ◽  
Vinh Ngo Minh ◽  
Hao Nguyen Trong ◽  
...  

BACKGROUND: Infected eczema is one of the most common complications of eczema. The progression and treatment of infected eczema have become more complex and difficulty due to the antibiotic resistance of bacteria and the abuse of antibiotics in treatment. AIM: Our research was conducted with the aim of investigating the severity of in vitro antibiotic resistance in patients with bacterially infected eczema at Ho Chi Minh City Hospital of Dermatology. METHODS: We studied 40 cases of patients, suffering from atopic dermatitis, contact dermatitis, vesicular palmoplantar eczema, with positive results of infected eczema. RESULTS: S. aureus accounted for 82.5%, followed by S. epidermidis (15%), P. aeruginosa (12.5%), S. pyogenes (5%) accounted for a small percentage. E. coli (2.5%) and M. morganii (2.5%) accounted for the lowest percentage. Both MSSA and MRSA were completely resistant to penicillin. MRSA is completely resistant to penicillin, erythromycin, and cefuroxime, highly resistant to clindamycin (82.35%). Our research showed that Pseudomonas aeruginosa was not resistant to a variety of antibiotics. It was completely resistant to tetracycline, trimethoprim/sulfamethoxazole (100%). Most bacteria are highly sensitive to linezolid, vancomycin as other studies in the world shown. There are also rifampicins, pristinamycin. Hence, it`s prioritised to be used for only patients with eczema infected with multidrug-resistant bacteria. CONCLUSION: Penicillin is not recommended for the treatment for infected eczema. Linezolid, vancomycin has a high sensitivity to bacteria including multidrug-resistant bacteria like MRSA.


2015 ◽  
Vol 13 (1) ◽  
Author(s):  
Emerson Danguy Cavassin ◽  
Luiz Francisco Poli de Figueiredo ◽  
José Pinhata Otoch ◽  
Marcelo Martins Seckler ◽  
Roberto Angelo de Oliveira ◽  
...  

2017 ◽  
Vol 83 (15) ◽  
Author(s):  
Mohammad Aminul Islam ◽  
Moydul Islam ◽  
Rashedul Hasan ◽  
M. Iqbal Hossain ◽  
Ashikun Nabi ◽  
...  

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.


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