Synergistic effect of antimicrobial peptide LL-37 and colistin combination against multidrug-resistant Escherichia coli isolates

2021 ◽  
Author(s):  
Gianluca Morroni ◽  
Laura Di Sante ◽  
Oriana Simonetti ◽  
Lucia Brescini ◽  
Wojciech Kamysz ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Synergistic Effect ◽  
Antimicrobial Peptide ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
E Coli ◽  
Antibiotic Effect ◽  
Global Spread ◽  
Time Kill ◽  
Post Antibiotic Effect

Overview: The global spread of antibiotic resistance represents a serious threat for public health. Aim: We evaluated the efficacy of the antimicrobial peptide LL-37 as antimicrobial agent against multidrug-resistant Escherichia coli. Results: LL-37 showed good activity against mcr-1 carrying, extended spectrum β-lactamase- and carbapenemase-producing E. coli (minimum inhibitory concentration, MIC, from 16 to 64 mg/l). Checkerboard assays demonstrated synergistic effect of LL-37/colistin combination against all tested strains, further confirmed by time–kill and post antibiotic effect assays. MIC and sub-MIC concentrations of LL-37 were able to reduce biofilm formation. Conclusion: Our preliminary data indicated that LL-37/colistin combination was effective against multidrug resistant E. coli strains and suggested a new possible clinical application.

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
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Membrane Integrity ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
E Coli ◽  
Minimal Media

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.

scholarly journals Pathogenic potential in catheter associated Escherichia coli is associated with separable biofilm and virulence gene determinants

2021 ◽  
Author(s):  
Zongsen Zou ◽  
Robert Potter ◽  
William McCoy ◽  
George Katumba ◽  
Peter J. Mucha ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Biofilm Formation ◽  
Gene Networks ◽  
Bacterial Colonization ◽  
Asymptomatic Bacteriuria ◽  
Virulence Gene ◽  
Multidrug Resistant ◽  
Pathogenic Potential ◽  
E Coli

Urinary catheterization facilitates asymptomatic bacterial colonization of the urinary tract and increases the risk of urinary tract infection (UTI). Differentiating catheter-associated asymptomatic bacteriuria (CAASB) from catheter-associated UTI (CAUTI) can be challenging when the presence or origins of symptoms are unclear. To determine whether strain-specific Escherichia coli characteristics are associated with CAUTI, we compared genomic composition and experimental catheter biofilm production by urinary isolates from catheterized inpatients and rectal isolates from healthy volunteers. CAUTI isolates were associated with a distinctive phylotype B2 sub-clade dominated by the multidrug resistant, pandemic ST131 lineage. While catheter biofilm formation was widespread among E. coli isolates, phylotype B2 biofilms were more extensive and biofilm-associated genes were preferentially found in B2 and ST131 isolates. Distinctive suites of iron-responsive genes were associated with both the ST131 lineage and catheter biofilm formation. Catheter biofilms produced by some CAASB strains could inhibit ST131 colonization, suggesting a potential beneficial function for these strains. These results suggest that the combination of biofilm and non-biofilm-associated gene networks in urinary E. coli influence CAUTI risk in catheterized patients.

scholarly journals 1054. Biofilm Formation Among Escherichia coli Bloodstream Infection Isolates Is Associated With Source of Bacteremia and Bacterial Sequence Type

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S315-S315
Author(s):  
Carolyn Chang ◽  
Felicia Ruffin ◽  
Vance G Fowler ◽  
Joshua T Thaden
Keyword(s):  
Escherichia Coli ◽  
Biofilm Formation ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Clinical Impact ◽  
Sequence Type ◽  
Apache Ii Score ◽  
E Coli ◽  
Biofilm Production ◽  
Bacterial Sequence

Abstract Background The clinical impact of Escherichia coli biofilm formation is unknown. Methods Adults with E. coli bloodstream infections (BSI) were prospectively enrolled from 2002 to 2015. All E. coli isolates were genotyped using Multilocus sequence typing (MLST) and underwent crystal violet biofilm formation assay quantified by absorbance at 540 nm (OD540) in triplicate. Associations between biofilm formation and patient/bacterial characteristics were characterized by t-tests and ANOVA tests. Results Ninety-eight percent (186) of the 189 isolates formed detectable biofilms. Bacterial sequence type (ST) was associated with biofilm formation (P < 0.001), as ST73 (average OD540 = 0.017) and ST393 (average OD540 = 0.016) had higher average biofilm formation while ST69 (average OD540 = 0.007) and ST405 (average OD540 = 0.002) had lower biofilm formation. E. coli isolates with non-multidrug-resistant (non-MDR) phenotype were associated with increased biofilm formation (MDR: average OD540 = 0.006; average non-MDR: OD540 = 0.01; P = 0.003). BSI isolates arising from pneumonia or urine/pyelonephritis were associated with the highest biofilm production (P = 0.04). No associations were identified between biofilm formation and route of infection, APACHE-II score, mortality, or complications of BSI. Conclusion In this prospective study of E. coli BSI isolates, biofilm formation was associated with ST, non-MDR phenotype, and BSI source. Disclosures All authors: No reported disclosures.

scholarly journals Synergy between Florfenicol and Aminoglycosides against Multidrug-Resistant Escherichia coli Isolates from Livestock

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 185 ◽  
Author(s):  
Shukho Kim ◽  
Jung Hwa Woo ◽  
So Hyun Jun ◽  
Dong Chan Moon ◽  
Suk-Kyung Lim ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Synergistic Effect ◽  
Antimicrobial Agents ◽  
Alternative Therapy ◽  
Multidrug Resistant ◽  
Combination Regimen ◽  
E Coli ◽  
Effective Combination

The increasing prevalence of antimicrobial resistance and the laborious development of novel antimicrobial agents have limited the options for effective antimicrobial therapy. The combination of previously used antimicrobial agents represents an alternative therapy for multidrug-resistant (MDR) pathogens. The objective of this study was to investigate the synergistic effect of a florfenicol (FFL)-based combination with other antimicrobial agents against MDR Escherichia coli isolates from livestock using checkerboard assays and murine infection models. The FFL/amikacin (AMK) and FFL/gentamicin (GEN) combinations showed synergy against 10/11 and 6/11 MDR E. coli isolates in vitro, respectively. The combination of FFL with aminoglycosides (AMK or GEN) exhibited a better synergistic effect against MDR E. coli isolates than the cephalothin (CEF)/GEN or FFL/CEF combinations. The combination of FFL with AMK or GEN could reduce the emergence of resistant mutants in vitro. The FFL/AMK combination showed a higher survival rate of mice infected with MDR E. coli isolates than FFL or AMK alone. In summary, the combination of FFL with aminoglycosides (AMK or GEN) is highly effective against MDR E. coli isolates both in vitro and in vivo. Our findings may contribute to the discovery of an effective combination regimen against MDR E. coli infections in veterinary medicine.

scholarly journals The Effects of β-Lactam Antibiotics on Surface Modifications of Multidrug-Resistant Escherichia coli: A Multiscale Approach

2019 ◽  
Vol 25 (1) ◽  
pp. 135-150 ◽  
Author(s):  
Samuel C. Uzoechi ◽  
Nehal I. Abu-Lail
Keyword(s):  
Escherichia Coli ◽  
Biofilm Formation ◽  
Bacterial Infections ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Multiscale Approach ◽  
Bacterial Cells ◽  
Adhesion Forces ◽  
E Coli ◽  
Resistant Strains

AbstractPossible multidrug-resistant (MDR) mechanisms of four resistant strains of Escherichia coli to a model β-lactam, ampicillin, were investigated using contact angle measurements of wettability, crystal violet assays of permeability, biofilm formation, fluorescence imaging, and nanoscale analyses of dimensions, adherence, and roughness. Upon exposure to ampicillin, one of the resistant strains, E. coli A5, changed its phenotype from elliptical to spherical, maintained its roughness and biofilm formation abilities, decreased its length and surface area, maintained its cell wall integrity, increased its hydrophobicity, and decreased its nanoscale adhesion to a model surface of silicon nitride. Such modifications are suggested to allow these cells to conserve energy during metabolic dormancy. In comparison, resistant strains E. coli D4, A9, and H5 elongated their cells, increased their roughness, increased their nanoscale adhesion forces, became more hydrophilic, and increased their biofilm formation upon exposure to ampicillin. These results suggest that these strains resisted ampicillin through biofilm formation that possibly introduces diffusion limitations to antibiotics. Investigations of how MDR bacterial cells modify their surfaces in response to antibiotics can guide research efforts aimed at designing more effective antibiotics and new treatment strategies for MDR bacterial infections.

Effect of the Association and Evaluation of the Induction to Adaptation of the (+)-α-pinene with Commercial Antimicrobials against Strains of Escherichia coli

2020 ◽  
Vol 20 (25) ◽  
pp. 2300-2307
Author(s):  
Felipe Lemos Esteves do Amaral ◽  
Ticiane Costa Farias ◽  
Raquel Carlos de Brito ◽  
Thamara Rodrigues de Melo ◽  
Paula Benvindo Ferreira ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Diffusion Method ◽  
Disk Diffusion Method ◽  
E Coli ◽  
Inappropriate Use ◽  
Microdilution Method ◽  
Antibiotic Effect ◽  
Bacterial Cell Membrane

Background: The increasing and inappropriate use of antibiotics has increased the number of multidrug-resistant microorganisms to these drugs, causing the emergence of infections that are difficult to control and manage by health professionals. As an alternative to combat these pathogens, some monoterpenes have harmful effects on the bacterial cell membrane, showing themselves as an alternative in combating microorganisms. Therefore, the positive enantiomer α -pinene becomes an alternative to fight bacteria, since it was able to inhibit the growth of the species Escherichia coli ATCC 25922, demonstrating the possibility of its use as an isolated antimicrobial or associated with other drugs. Aims: The aim of this study is to evaluate the sensitivity profile of E. coli ATCC 25922 strain against clinical antimicrobials associated with (+) -α-pinene and how it behaves after successive exposures to subinhibitory concentrations of the phytochemicals. Methods: : The minimum inhibitory concentration (MIC) was determined using the microdilution method. The study of the modulating effect of (+) -α-pinene on the activity of antibiotics for clinical use in strains of E. coli and the analysis of the strain's adaptation to the monoterpene were tested using the adapted disk-diffusion method. Results: The results demonstrate that the association of monoterpene with the antimicrobials ceftazidime, amoxicillin, cefepime, cefoxitin and amikacin is positive since it leads to the potentiation of the antibiotic effect of these compounds. It was observed that the monoterpene was able to induce crossresistance only for antimicrobials: cefuroxime, ceftazidime, cefepime and chloramphenicol. Conclusion: It is necessary to obtain more concrete data for the safe use of these combinations, paying attention to the existence of some type of existing toxicity reaction related to the herbal medicine and to understand the resistance mechanisms acquired by the microorganism.

In Vitro Synergism of Sulbactam- Cefoperazone and Fosfomycin Against Escherichia Coli and Klebsiella Aeromobilis from Indonesia

2021 ◽  
Vol 71 (5) ◽  
pp. 209-214
Author(s):  
Agus Syahrurachman ◽  
Atna Permana
Keyword(s):  
Inhibitory Concentration ◽  
Clinical Laboratory ◽  
Independent Effect ◽  
E Coli ◽  
Susceptibility Data ◽  
Antibiotic Effect ◽  
Time Kill ◽  
Checkerboard Titration ◽  
Post Antibiotic Effect

Introduction: There is no susceptibility data of E. coli and K. aeromobilis in Indonesia, even data regarding minimal inhibitory concentration (MIC)-based susceptibility of E. coli and K. aeromobilis towards single antibiotic or combination of fosfomycin (FOS) and sulbactam-cepoferazone (SUL-CPZ) is very scarce, even though the data is required by clinicians. Methods: A descriptive observational study was carried out at the Microbiology Clinical Laboratory of the Faculty of Medicine, Universitas Indonesia. Thirty strains each of clinical isolates of E. coli and K. aeromobilis were subjected to MIC determination against FOS and SUL-CPZ. For susceptibility criteria, we adopted the Eucast guideline. The synergism of the combined antibiotics was determined by checkerboard titration. One strain of E. coli and K. aeromobilis showing a synergistic and independent effect against the combined antibiotics was subjected to a time-kill assay. The post-antibiotic effect (PAE) was determined on a strain of E. coli showing synergism against the combined antibiotics. Results: The MIC level of all strains decreased when the bacteria were exposed to the combined antibiotics. Synergism was observed in 53.3% of E. coli and 56.8% of K. aeromobilis. No antagonism was observed. Higher bacterial death during the first four hours occurred with the isolate, showing synergism compared to the isolate showing an independent effect. The PAE of E. coli was longer when exposed to combined antibiotics. Conclusion: In vitro synergism of FOS and SUL-CPZ was observed in the majority of isolates and could be used as the basis for further research on empirical treatment

scholarly journals A Novel Trimethoprim Resistance Gene, dfrA36, Characterized from Escherichia coli from Calves

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Dominik Wüthrich ◽  
Michael Brilhante ◽  
Anna Hausherr ◽  
Jens Becker ◽  
Mireille Meylan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Multidrug Resistant ◽  
Content Type ◽  
Genetic Link ◽  
E Coli ◽  
Global Spread ◽  
Different Sources ◽  
Disinfectant Resistance

The presence of dfrA36 associated with ISCR2 in Escherichia coli from animals, as well as its presence in other E. coli strains from different sources and countries and in Acinetobacter, highlights the global spread of this gene and its potential for further dissemination. The genetic link of ISCR2-dfrA36 with other antibiotic and disinfectant resistance genes showed that multidrug-resistant E. coli may be selected and maintained by the use of either one of several antimicrobials.

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