scholarly journals Heterogeneous Absorption of Antimicrobial Peptide LL37 inEscherichia coliCells Enhances Population Survivability

2018 ◽  
Author(s):  
Mehdi Snoussi ◽  
John Paul Talledo ◽  
Nathan-Alexander Del Rosario ◽  
Bae-Yeun Ha ◽  
Andrej Košmrlj ◽  
...  

AbstractAntimicrobial peptides (AMPs) are broad spectrum antibiotics that selectively target bacteria. Here we investigate the activity of human AMP LL37 againstEscherichia coliby integrating quantitative, population and single-cell level experiments with theoretical modeling. Our data indicate an unexpected, rapid absorption and retention of a large number of LL37 byE. colicells upon the inhibition of their growth, which increases the chance of survival for the rest of population. Cultures with high-enough cell density exhibit two distinct subpopulations: a non-growing population that absorb peptides and a growing population that survive owing to the sequestration of the AMPs by others. A mathematical model based on this binary picture reproduces the rather surprising behaviors ofE. colicultures in the presence of LL37, including the increase of the minimum inhibitory concentration with cell density (even in dilute cultures) and the extensive lag in growth introduced by sub-lethal dosages of LL37.

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Mehdi Snoussi ◽  
John Paul Talledo ◽  
Nathan-Alexander Del Rosario ◽  
Salimeh Mohammadi ◽  
Bae-Yeun Ha ◽  
...  

Antimicrobial peptides (AMPs) are broad spectrum antibiotics that selectively target bacteria. Here we investigate the activity of human AMP LL37 against Escherichia coli by integrating quantitative, population and single-cell level experiments with theoretical modeling. We observe an unexpected, rapid absorption and retention of a large number of LL37 peptides by E. coli cells upon the inhibition of their growth, which increases population survivability. This transition occurs more likely in the late stage of cell division cycles. Cultures with high cell density exhibit two distinct subpopulations: a non-growing population that absorb peptides and a growing population that survive owing to the sequestration of the AMPs by others. A mathematical model based on this binary picture reproduces the rather surprising observations, including the increase of the minimum inhibitory concentration with cell density (even in dilute cultures) and the extensive lag in growth introduced by sub-lethal dosages of LL37 peptides.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Abdulkader Masri ◽  
Naveed Ahmed Khan ◽  
Muhammad Zarul Hanifah Md Zoqratt ◽  
Qasim Ayub ◽  
Ayaz Anwar ◽  
...  

Abstract Backgrounds Escherichia coli K1 causes neonatal meningitis. Transcriptome studies are indispensable to comprehend the pathology and biology of these bacteria. Recently, we showed that nanoparticles loaded with Hesperidin are potential novel antibacterial agents against E. coli K1. Here, bacteria were treated with and without Hesperidin conjugated with silver nanoparticles, and silver alone, and 50% minimum inhibitory concentration was determined. Differential gene expression analysis using RNA-seq, was performed using Degust software and a set of genes involved in cell stress response and metabolism were selected for the study. Results 50% minimum inhibitory concentration with silver-conjugated Hesperidin was achieved with 0.5 μg/ml of Hesperidin conjugated with silver nanoparticles at 1 h. Differential genetic analysis revealed the expression of 122 genes (≥ 2-log FC, P< 0.01) in both E. coli K1 treated with Hesperidin conjugated silver nanoparticles and E. coli K1 treated with silver alone, compared to untreated E. coli K1. Of note, the expression levels of cation efflux genes (cusA and copA) and translocation of ions, across the membrane genes (rsxB) were found to increase 2.6, 3.1, and 3.3- log FC, respectively. Significant regulation was observed for metabolic genes and several genes involved in the coordination of flagella. Conclusions The antibacterial mechanism of nanoparticles maybe due to disruption of the cell membrane, oxidative stress, and metabolism in E. coli K1. Further studies will lead to a better understanding of the genetic mechanisms underlying treatment with nanoparticles and identification of much needed novel antimicrobial drug candidates.


DICP ◽  
1989 ◽  
Vol 23 (6) ◽  
pp. 456-460
Author(s):  
Michael N. Dudley ◽  
Hilary D. Mandler ◽  
Kenneth H. Mayer ◽  
Stephen H. Zinner

Serum inhibitory and bactericidal titers were measured in nine healthy volunteers following single iv doses of ciprofloxacin 100, 150, and 200 mg. The median peak serum bactericidal titer (5 minutes following completion of a 30-minute infusion) against two highly susceptible strains of Escherichia coli ranged between 1:64 and 1:1024 and titers exceeded 1:8 for six hours for all dose levels. The bactericidal titers against two strains of Pseudomonas aeruginosa and a methicillin-resistant strain of Staphylococcus aureus were considerably lower, the median peak being 1:2 at all dose levels. Measured inhibitory and bactericidal titers at five minutes and one hour postinfusion were significantly greater than those predicted (measured serum ciprofloxacin concentration to minimum inhibitory concentration [MIC] or minimum bactericidal concentration [MBC]) for only one strain of E. coli. Intravenous doses of ciprofloxacin 100–200 mg produce high and sustained serum bactericidal titers against highly susceptible bacteria; considerably lower levels of activity are seen against bacteria having higher MICs and MBCs but still considered susceptible to the drug.


2014 ◽  
Vol 112 (1) ◽  
pp. 178-183 ◽  
Author(s):  
Julia Bos ◽  
Qiucen Zhang ◽  
Saurabh Vyawahare ◽  
Elizabeth Rogers ◽  
Susan M. Rosenberg ◽  
...  

Bacteria can rapidly evolve resistance to antibiotics via the SOS response, a state of high-activity DNA repair and mutagenesis. We explore here the first steps of this evolution in the bacteriumEscherichia coli. Induction of the SOS response by the genotoxic antibiotic ciprofloxacin changes theE. colirod shape into multichromosome-containing filaments. We show that at subminimal inhibitory concentrations of ciprofloxacin the bacterial filament divides asymmetrically repeatedly at the tip. Chromosome-containing buds are made that, if resistant, propagate nonfilamenting progeny with enhanced resistance to ciprofloxacin as the parent filament dies. We propose that the multinucleated filament creates an environmental niche where evolution can proceed via generation of improved mutant chromosomes due to the mutagenic SOS response and possible recombination of the new alleles between chromosomes. Our data provide a better understanding of the processes underlying the origin of resistance at the single-cell level and suggest an analogous role to the eukaryotic aneuploidy condition in cancer.


2019 ◽  
Vol 21 (6) ◽  
pp. 280-283
Author(s):  
Farshad Kakian ◽  
Behnam Zamanzad ◽  
Abolfazle Gholipour ◽  
Kiarash Zamanzad

Background and aims: Carbapenems are the final-line treatments for multidrug-resistant, gram-negative infections. The patterns of resistance to carbapenems among hospital bacterial pathogens vary widely across different hospitals in a country. Considering that Escherichia coli is one of the most important causes of nosocomial infections, it is essential to study its drug resistance. Methods: In this descriptive-analytical study, a total of 80 samples of E. coli isolated from inpatients with urinary tract infections (UTIs) were collected in different wards (i.e., women, urology, infectious, and ICU) of Shahrekord hospitals. After the diagnosis and confirmation of bacteria by standard bacteriological methods, their sensitivity to imipenem and meropenem was investigated by the antibiogram (diskdiffusion) method. Then, the minimum inhibitory concentration (MIC) was determined by the E-test strip according to the Clinical and Laboratory Standards Institute (CLSI) standard. Results: In this study, resistance to meropenem and imipenem by antibiogram (disc diffusion) was observed in 21 (25.26%) and 20 (25%) of the isolates, respectively. Twenty isolates had MIC ≥4 μg/mL for meropenem, 13 isolates demonstrated MIC≥4 μg/mL for imipenem, and 14 isolates had 1≤MIC<4 μg/mL and were semi-sensitive. Conclusion: In general, E. coli had significant resistance to carbapenems. Therefore, rapid and accurate identification of these strains can be a major step to the treatment and control of these strains and prevention of the spread of the resistance.


2017 ◽  
Vol 14 (1) ◽  
Author(s):  
Samuel Hager ◽  
Ellen Jensen ◽  
Timothy Johnson ◽  
David Mitchell

Bacteria are quick to adapt and evolve, especially under the effects of selective pressures from chemical antibiotics. In addition, bacteria may develop resistance to antibiotics from multiple classes simultaneously, making their eradication from the human body particularly challenging. This study aims to demonstrate that bacterial multiple-drug resistance can be developed and retained in a laboratory setting. Escherichia coli B was grown in tryptic soy broth in the presence of a small, increasing concentration of streptomycin. This exposure resulted in a strain of E. coli, which had an increased minimum inhibitory concentration (MIC) towards streptomycin, or “resistance.” This resistant strain was then grown in like manner in nalidixic acid and then penicillin G. The result was a strain that became resistant to streptomycin and nalidixic acid, and increasingly resistant to nalidixic acid after penicillin G exposure. Additionally, the bacteria retained resistance to streptomycin and nalidixic acid even after exposure to those chemicals ceased. Genome sequencing and comparison to E. coli B reference strain REL606 revealed the emergence of point mutations with each exposure to an antibiotic. Of particular interest is a mutation associated with the appearance of nalidixic acid resistance. Base pair 4,553,488 was changed from adenine to guanine, resulting in a change from aspartate to glycine in the protein helicase. Previous studies have not indicated mutations to this locus as nalidixic acid resistance conferring. Thus, this mutation may be a novel mutation conferring E. coli B nalidixic acid resistance. Since the region of the mutated helicase is functionally undefined, a mechanism is not apparent. Further research needs to be done to confirm this hypothesis and illuminate a mechanism. KEYWORDS: Bacteria; Escherichia coli; Evolution; Antibiotic Resistance; Nalidixic Acid; Streptomycin; Point Mutation; Single-nucleotide Polymorphism; Helicase; Minimum Inhibitory Concentration


2020 ◽  
Vol 7 (2) ◽  
pp. 289-295
Author(s):  
Mohammad Arfi Setiawan ◽  
Mita Dewi Retnoningrum ◽  
Febriyandhi Yahya ◽  
Resa Ragil Andika ◽  
Dyan Hatining Ayu Sudarni

Antibacterial Activity of Citrus seed (Citrus reticulata) Extract on Escherichia coli Indonesian agriculture provides a resource of medicinal plants whose potential needs to be explored in order to benefit society. One of them is the use of Siam orange seeds (Citrus reticulata) which has the potential for the production of antibacterial compounds. This study aims to test the antibacterial activity of the ethanol and n-hexane extract of orange seeds. The extract was obtained through maceration techniques using ethanol and n-hexane as solvents. The antibacterial activity test of orange seeds against Escherichia coli used the paper disc diffusion method with nutrient agar (NA) media. The concentration of orange seed extract for the determination of MIC (Minimum Inhibitory Concentration) was 0.5, 2, 8, 10, 20 mg mL-1. The results showed that the ethanol and n-hexane extract of orange seeds had antibacterial activity against E. coli. However, the ethanol extract had a higher antibacterial effect than the n-hexane orange seed extract. From the results of this study, it is hoped that the waste of orange seeds will provide beneficial contribution for pharmaceutical development. Pertanian Indonesia memiliki sumber tanaman obat yang perlu digali potensinya agar bermanfaat bagi masyarakat. Salah satunya pemanfaatan biji jeruk siam (Citrus reticulata) yang berpotensi menghasilkan senyawa antibakteri. Penelitian ini bertujuan untuk menguji aktivitas antibakteri ekstrak etanol dan n-heksana biji jeruk. Ekstrak diperoleh melalui teknik maserasi menggunakan pelarut etanol dan n-heksana. Uji aktivitas antibakteri biji jeruk terhadap Escherichia coli menggunakan metode difusi paper disc dengan media nutrient agar (NA). Konsentrasi ekstrak biji jeruk untuk penentuan MIC (Minimum Inhibitory Concentration) adalah 0,5, 2, 8, 10, 20 mg mL-1. Hasil penelitian menunjukkan bahwa ekstrak etanol dan n-heksana biji jeruk memiliki aktivitas antibakteri terhadap E. coli. Namun, ekstrak etanol memiliki efek antibakteri yang lebih tinggi dibandingkan ekstrak biji jeruk n-heksana. Dari hasil penelitian ini, limbah biji jeruk diharapkan dapat memberikan kontribusi bermanfaat bagi pengembangan farmasi.


2016 ◽  
Vol 144 (14) ◽  
pp. 2967-2970 ◽  
Author(s):  
D. ORTEGA-PAREDES ◽  
P. BARBA ◽  
J. ZURITA

SUMMARYColistin resistance mediated by the mcr-1 gene has been reported worldwide, but to date not from the Andean region, South America. We report the first clinical isolate of Escherichia coli harbouring the mcr-1 gene in Ecuador. The strain was isolated from peritoneal fluid from a 14-year-old male with acute appendicitis, and subjected to molecular analysis. The minimum inhibitory concentration of colistin for the strain was 8 mg/ml and it was susceptible to carbapenems but resistant to tigecycline. The strain harboured mcr-1 and blaCTX-M-55 genes and was of sequence type 609. The recognition of an apparently commensal strain of E. coli harbouring mcr-1 serves as an alert to the presence in the region of this recently described resistance mechanism to one of the last line of drugs available for the treatment of multi-resistant Gram-negative infections.


2019 ◽  
Vol 86 (3) ◽  
Author(s):  
Wenchao Zhang ◽  
Yan Wang ◽  
Huining Lu ◽  
Qin Liu ◽  
Chuandong Wang ◽  
...  

ABSTRACT The predatory behavior of Myxococcus xanthus has attracted extensive attention due to its unique social traits and inherent biological activities. In addition to group hunting, individual M. xanthus cells are able to kill and lyse prey cells; however, there is little understanding of the dynamics of solitary predation. In this study, by employing a bacterial tracking technique, we investigated M. xanthus predatory dynamics on Escherichia coli at the single-cell level. The killing and lysis of E. coli by a single M. xanthus cell was monitored in real time by microscopic observation, and the plasmolysis of prey cells was identified at a relatively early stage of solitary predation. After quantitative characterization of their solitary predatory behavior, M. xanthus cells were found to respond more dramatically to direct contact with live E. coli cells than heat-killed or UV-killed cells, showing slower predator motion and faster lysing of prey. Among the three contact-dependent killing modes classified according to the major subareas of M. xanthus cells in contact with prey, leading pole contact was observed most. After killing the prey, approximately 72% of M. xanthus cells were found to leave without thorough degradation of the lysed prey, and this postresidence behavior is described as a lysis-leave pattern, indicating that solitary predation has low efficiency in terms of prey-cell consumption. Our results provide a detailed description of the single-cell level dynamics of M. xanthus solitary predation from both prey and predator perspectives. IMPORTANCE Bacterial predation plays multiple essential roles in bacterial selection and mortality within microbial ecosystems. In addition to its ecological and evolutionary importance, many potential applications of bacterial predation have been proposed. The myxobacterium Myxococcus xanthus is a well-known predatory member of the soil microbial community. Its predation is commonly considered a collective behavior comparable to a wolf pack attack; however, individual M. xanthus cells are also able to competently lead to the lysis of a prey cell. Using a bacterial tracking technique, we are able to observe and analyze solitary predation by M. xanthus on Escherichia coli at the single-cell level and reveal the dynamics of both predator and prey during the process. The present study will not only provide a comprehensive understanding of M. xanthus solitary predation but also help to explain why M. xanthus often displays multicellular characteristic predatory behaviors in nature, while a single cell is capable of predation.


Author(s):  
Phan Vu Hai ◽  
Hoang Thi Hong Van ◽  
Nguyen Van Chao ◽  
Nguyen Dinh Thuy Khuong ◽  
Thuong Thi Thanh Le ◽  
...  

The chives and ginger’s bulbs were extracted by ethanol 96%, 72%, 48% within 5, 10 and 15 days for each concentration (15, 30 and 45 days in total, respectively). The solidified extract then was used for antibacterial activity against E. coli and Salmonella spp. isolated from fecal of chickens with diarrhoea. The results showed that both ginger and chive, which socked and leached for greater than 30 days gave better antibacterial ability. Extracts diluted at concentrations of 5 µg/µl, 7.5 µg/µl and 10 µg/µl of ginger and chive bulbs are resistant to both bacteria. Compared with antibiotics, E. coli was resistant to amoxicillin, whereas Salmonella spp. was resistant to gentamicin and amoxicillin. The minimum inhibitory concentration (MIC) of chives extract (30 days) was 16-63 (31-125) mg/ml and ginger extract (30 days) was 16-80 (2-4) mg/ml; overall, the results indicated that both extract had bacteriostatic/bactericidal effects on E. coli and Salmonella spp.


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