scholarly journals Comparison of Polymyxin E and Polymyxin B as an Additive to Pulmonary Surfactant in Escherichia coli Pneumonia of Ventilated Neonatal Rabbits

2017 ◽  
Vol 2 (2) ◽  
pp. 1-9 ◽  
Author(s):  
Guido Stichtenoth ◽  
Marie Haegerstrand-Björkman ◽  
Gabi Walter ◽  
Bim Linderholm ◽  
Egbert Herting ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Growth ◽  
Pulmonary Surfactant ◽  
Bacterial Infections ◽  
Bacterial Load ◽  
Polymyxin B ◽  
Lung Compliance ◽  
Antimicrobial Treatment ◽  
E Coli ◽  
Polymyxin E

Background: Ascending maternofetal bacterial infections often result in premature birth and neonatal respiratory distress. These neonates are treated with exogenous pulmonary surfactant (SF) and systemic antibiotics. Polymyxins are antimicrobiotic peptides that may bind to SF phospholipids. Objectives: Does topical administration of SF/polymyxin reduce bacterial growth in neonatal rabbit pneumonia and improve pulmonary function? Methods: Neonatal rabbits were tracheotomized and treated intratracheally with mixtures of porcine SF, SF/polymyxin E (PxE), or polymyxin B (PxB). Control animals received saline. Animals were then inoculated with Escherichia coli and ventilated for 4 h. During the experiment, peak insufflation pressures, dynamic lung compliance, and ECG were recorded. Pulmonary and renal bacterial load were determined. Lung histology was performed. Lung and kidney IL-8 were measured in subgroups. Results: Eighty-five animals were included in 2 experimental series, of which 78% survived 4 h of ventilation. E. coli inoculation caused severe neonatal pneumonia with median IL-8 levels of 2.2 ng/g in the lungs compared to a median of 0.2 ng/g in the lungs of the saline controls (p < 0.01). Lung compliance after 4 h was significantly increased at a mean of 0.48 ml/(kg·cm H2O) in the SF group and 0.43 in the SF + PxE group compared to 0.35 in the E. coli group (p < 0.01). In direct comparison, bacterial growth found in the E. coli group was reduced 20-fold in the SF + PxB group compared to 75-fold in the SF + PxE group. Conclusion: Addition of polymyxin to SF effectively promotes antimicrobial treatment and improves lung function in neonatal pneumonia of rabbits.

Two Novel Mutations Associated with Polymyxin-B Resistance in a Pandemic Lineage of Uropathogenic Escherichia coli of the Sequence Type 69

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Carla Adriana dos Santos ◽  
Rodrigo Tavanelli Hernandes ◽  
Marcos Paulo Vieira Cunha ◽  
Filipe Onishi Nagamori ◽  
Claudia Regina Gonçalves ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Susceptibility Testing ◽  
Polymyxin B ◽  
Antimicrobial Treatment ◽  
Sequence Type ◽  
Broth Microdilution ◽  
Economic Costs ◽  
Novel Mutations ◽  
E Coli ◽  
Total Inhibition

<b><i>Background:</i></b> Uropathogenic <i>Escherichia coli</i> (UPEC) are frequent pathogens worldwide, impacting on the morbidity and economic costs associated with antimicrobial treatment. <b><i>Objectives:</i></b> We report two novel mutations associated with polymyxin-B resistance in an UPEC isolate collected in 2019. <b><i>Methods:</i></b> Isolate was submitted to antimicrobial susceptibility testing including broth microdilution for polymyxin B. Whole genome was sequenced and analyzed. <b><i>Results:</i></b> Polymyxin-B total inhibition occurred at 16 mg/L (resistant). UPEC isolate was assigned to the phylogroup D, serotype O117:H4, and Sequence Type 69. <i>mcr</i> genes were not detected, but two novel mutations in the <i>pmrA/basS</i> (A80S) and <i>pmrB/</i>basR (D149N) genes were identified. <b><i>Conclusions:</i></b> The occurrence of non-<i>mcr</i> polymyxin resistance in <i>E. coli</i> from extraintestinal infections underscores the need of a continuous surveillance of this evolving pathogen.

scholarly journals Restriction of bacterial growth by inhibition of polyamine biosynthesis by using monofluoromethylornithine, difluoromethylarginine and dicyclohexylammonium sulphate

1982 ◽  
Vol 208 (2) ◽  
pp. 435-441 ◽  
Author(s):  
A J Bitonti ◽  
P P McCann ◽  
A Sjoerdsma
Keyword(s):  
Escherichia Coli ◽  
Ornithine Decarboxylase ◽  
Bacterial Growth ◽  
Active Site ◽  
Bacterial Infections ◽  
Polyamine Biosynthesis ◽  
E Coli ◽  
Subsequent Investigation ◽  
Generation Times ◽  
Viable Approach

Bacterial growth was measurably slowed by a combination of drugs which inhibit polyamine-biosynthetic enzymes. Addition of DL-alpha-monofluoromethylornithine, which was shown to inactivate irreversibly ornithine decarboxylase extracted from Escherichia coli (Ki = 0.36 mM) and Pseudomonas aeruginosa (Ki = 0.30 mM), DL-alpha-difluoromethylarginine and dicyclohexylammonium sulphate to cultures of E. coli or P. aeruginosa resulted in a 40 and 70% increase in generation times (decreased growth rates) respectively, which was completely reversed by the addition of 0.1 mM-putrescine plus 0.1 mM-spermidine to the medium. Decreased intracellular polyamine concentrations correlated with increased generation times; putrescine concentration was decreased by 70% in E. coli and 80% in P. aeruginosa, while spermidine concentration was decreased by 50% in E. coli and 95% in P. aeruginosa. Subsequent investigation of the inactivation of the ornithine decarboxylase by monofluoromethylornithine indicated that it was active-site directed, as the normal substrate ornithine slowed the rate of inhibition. Specific interference with polyamine biosynthesis may be a viable approach to control of some bacterial infections.

scholarly journals Transcriptome changes and polymyxin resistance of acid-adapted Escherichia coli O157:H7 ATCC 43889

Gut Pathogens ◽  
2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Daekeun Hwang ◽  
Seung Min Kim ◽  
Hyun Jung Kim
Keyword(s):  
Escherichia Coli ◽  
Acid Treatment ◽  
Bacterial Infections ◽  
Acid Tolerance ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Health Concern ◽  
E Coli ◽  
Tolerance Response ◽  
Acid Tolerant

Abstract Background Acid treatment is commonly used for controlling or killing pathogenic microorganisms on medical devices and environments; however, inadequate acid treatment may cause acid tolerance response (ATR) and offer cross-protection against environmental stresses, including antimicrobials. This study aimed to characterise an Escherichia coli strain that can survive in the acidic gastrointestinal environment. Results We developed an acid-tolerant E. coli O157:H7 ATCC 43889 (ATCC 43889) strain that can survive at pH 2.75 via cell adaptation in low pH conditions. We also performed RNA sequencing and qRT-PCR to compare differentially expressed transcripts between acid-adapted and non-adapted cells. Genes related to stress resistance, including kdpA and bshA were upregulated in the acid-adapted ATCC 43889 strain. Furthermore, the polymyxin resistance gene arnA was upregulated in the acid-adapted cells, and resistance against polymyxin B and colistin (polymyxin E) was observed. As polymyxins are important antibiotics, effective against multidrug-resistant gram-negative bacterial infections, the emergence of polymyxin resistance in acid-adapted E. coli is a serious public health concern. Conclusion The transcriptomic and phenotypic changes analysed in this study during the adaptation of E. coli to acid environments can provide useful information for developing intervention technologies and mitigating the risk associated with the emergence and spread of antimicrobial resistance.

scholarly journals Different effects of transcriptional regulators MarA, SoxS and Rob on susceptibility of Escherichia coli to cationic antimicrobial peptides (CAMPs): Rob-dependent CAMP induction of the marRAB operon

Microbiology ◽  
2010 ◽  
Vol 156 (2) ◽  
pp. 570-578 ◽  
Author(s):  
Douglas M. Warner ◽  
Stuart B. Levy
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptides ◽  
Bacterial Infections ◽  
Transcriptional Regulators ◽  
Polymyxin B ◽  
Cationic Antimicrobial Peptides ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Camp Induction ◽  
Increased Susceptibility

Cationic antimicrobial peptides (CAMPs), a component of the mammalian immune system, protect the host from bacterial infections. The roles of the Escherichia coli transcriptional regulators MarA, SoxS and Rob in susceptibility to these peptides were examined. Overexpression of marA, either in an antibiotic-resistant marR mutant or from a plasmid, decreased bacterial susceptibility to CAMPs. Overexpression of the soxS gene from a plasmid, which decreased susceptibility to antibiotics, unexpectedly caused no decrease in CAMP susceptibility; instead it produced increased susceptibility to different CAMPs. Deletion or overexpression of rob had little effect on CAMP susceptibility. The marRAB operon was upregulated when E. coli was incubated in sublethal amounts of CAMPs polymyxin B, LL-37 or human β-defensin-1; however, this upregulation required Rob. Deletion of acrAB increased bacterial susceptibility to polymyxin B, LL-37 and human β-defensin-1 peptides. Deletion of tolC yielded an even greater increase in susceptibility to these peptides and also led to increased susceptibility to human α-defensin-2. Inhibition of cellular proton-motive force increased peptide susceptibility for wild-type and acrAB deletion strains; however, it decreased susceptibility of tolC mutants. These findings demonstrate that CAMPs are both inducers of marA-mediated drug resistance through interaction with Rob and also substrates for efflux in E. coli. The three related transcriptional regulators show different effects on bacterial cell susceptibility to CAMPs.

scholarly journals Critical Role of 3′-Downstream Region of pmrB in Polymyxin Resistance in Escherichia coli BL21(DE3)

2021 ◽  
Vol 9 (3) ◽  
pp. 655
Author(s):  
Fuzhou Xu ◽  
Atsushi Hinenoya ◽  
Ximin Zeng ◽  
Xing-Ping Li ◽  
Ziqiang Guan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Lipid A ◽  
Mrna Level ◽  
Critical Role ◽  
Polymyxin B ◽  
Colistin Resistance ◽  
E Coli ◽  
Escherichia Coli Bl21 ◽  
Downstream Region

Polymyxins, such as colistin and polymyxin B, are the drugs used as a last resort to treat multidrug-resistant Gram-negative bacterial infections in humans. Increasing colistin resistance has posed a serious threat to human health, warranting in-depth mechanistic research. In this study, using a functional cloning approach, we examined the molecular basis of colistin resistance in Escherichia coli BL21(DE3). Five transformants with inserts ranging from 3.8 to 10.7 kb displayed significantly increased colistin resistance, three of which containing pmrB locus and two containing pmrD locus. Stepwise subcloning indicated that both the pmrB with a single G361A mutation and at least a 103 bp downstream region of pmrB are essential for conferring colistin resistance. Analysis of the mRNA level and stability showed that the length of the downstream region drastically affected the pmrB mRNA level but not its half-life. Lipid A analysis, by mass spectrometry, revealed that the constructs containing pmrB with a longer downstream region (103 or 126 bp) have charge-altering l-4-aminoarabinose (Ara4N) and phosphoethanolamine (pEtN) modifications in lipid A, which were not observed in both vector control and the construct containing pmrB with an 86 bp downstream region. Together, the findings from this study indicate that the 3′-downstream region of pmrB is critical for the PmrB-mediated lipid A modifications and colistin resistance in E. coli BL21(DE3), suggesting a novel regulatory mechanism of PmrB-mediated colistin resistance in E. coli.

scholarly journals A New Surface Charge Neutralizing Nano-Adjuvant to Potentiate Polymyxins in Killing Mcr-1 Mediated Drug-Resistant Escherichia coli

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 250
Author(s):  
Hyejin Cho ◽  
Atanu Naskar ◽  
Sohee Lee ◽  
Semi Kim ◽  
Kwang-Sun Kim
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Underlying Mechanism ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Gene Products ◽  
Physical Status ◽  
Cellular Gene ◽  
Gram Negative ◽  
E Coli

Resistance to polymyxins when treating multidrug-resistant (MDR) Gram-negative bacterial infections limit therapeutic options. Here, we report the synthesis of a nickel (Ni) doped Zinc oxide (NZO) combined with black phosphorus (BP) (NZB) nanocomposite and its synergistic action with polymyxin B (PolB) against polymyxin-resistant Escherichia coli harboring mobilized colistin resistance (mcr-1) gene. NZB and PolB combination therapy expressed a specific and strong synergy against Mcr-1 expressing E. coli cells. The underlying mechanism of the synergy is the charge neutralization of the E. coli cell surface by NZB, resulting in a more feasible incorporation of PolB to E. coli. The synergistic concentration of NZB with PolB was proved biocompatible. Thus, the NZB is the first biocompatible nano-adjuvant to polymyxins against polymyxin-resistant E. coli cells, recognizing the physical status of bacteria instead of known adjuvants targeting cellular gene products. Therefore, NZB has the potential to revive polymyxins as leading last-resort antibiotics to combat polymyxin-resistant Gram-negative bacterial infections.

scholarly journals Three-Year Trend in Escherichia coli Antimicrobial Resistance among Children’s Urine Cultures in an Italian Metropolitan Area

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 597
Author(s):  
Luca Pierantoni ◽  
Laura Andreozzi ◽  
Simone Ambretti ◽  
Arianna Dondi ◽  
Carlotta Biagi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metropolitan Area ◽  
Bacterial Infections ◽  
Asymptomatic Bacteriuria ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
First Line ◽  
E Coli ◽  
First Line Therapy ◽  
Tract Infections

Urinary tract infections (UTIs) are among the most common bacterial infections in children, and Escherichia coli is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. Given the current increasing rates of antibiotic resistance worldwide, this study aimed to investigate the three-year trend in the resistance rate of E. coli isolated from pediatric urine cultures (UCs) in a metropolitan area of northern Italy. We conducted a retrospective review of E. coli-positive, non-repetitive UCs collected in children aged from 1 month to 14 years, regardless of a diagnosis of UTI, catheter colonization, urine contamination, or asymptomatic bacteriuria. During the study period, the rate of resistance to AMC significantly increased from 17.6% to 40.2% (p < 0.001). Ciprofloxacin doubled its resistance rate from 9.1% to 16.3% (p = 0.007). The prevalence of multidrug-resistant E. coli rose from 3.9% to 9.2% (p = 0.015). The rate of resistance to other considered antibiotics remained stable, as did the prevalence of extended spectrum beta-lactamases and extensively resistant E. coli among isolates. These findings call into question the use of AMC as a first-line therapy for pediatric UTIs in our population, despite the indications of recent Italian guidelines.

scholarly journals Mechanistic insights into synergy between nalidixic acid and tetracycline against clinical isolates of Acinetobacter baumannii and Escherichia coli

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Nalidixic Acid ◽  
Bacterial Infections ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Infection Model ◽  
Drug Resistant ◽  
E Coli

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)

Alteration of the phagocytosis and antimicrobial defense of Octodonta nipae (Coleoptera: Chrysomelidae) pupae to Escherichia coli following parasitism by Tetrastichus brontispae (Hymenoptera: Eulophidae)

2018 ◽  
Vol 109 (2) ◽  
pp. 248-256
Author(s):  
E. Meng ◽  
J. Li ◽  
B. Tang ◽  
Y. Hu ◽  
T. Qiao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Response ◽  
Immune Responses ◽  
Mrna Expression ◽  
Bactericidal Activity ◽  
Bacterial Infections ◽  
Expression Level ◽  
Primary Immune Response ◽  
Mrna Expression Level ◽  
E Coli

AbstractAlthough parasites and microbial pathogens are both detrimental to insects, little information is currently available on the mechanism involved in how parasitized hosts balance their immune responses to defend against microbial infections. We addressed this in the present study by comparing the immune response between unparasitized and parasitized pupae of the chrysomelid beetle, Octodonta nipae (Maulik), to Escherichia coli invasion. In an in vivo survival assay, a markedly reduced number of E. coli colony-forming units per microliter was detected in parasitized pupae at 12 and 24 h post-parasitism, together with decreased phagocytosis and enhanced bactericidal activity at 12 h post-parasitism. The effects that parasitism had on the mRNA expression level of selected antimicrobial peptides (AMPs) of O. nipae pupae showed that nearly all transcripts of AMPs examined were highly upregulated during the early and late parasitism stages except defensin 2B, whose mRNA expression level was downregulated at 24 h post-parasitism. Further elucidation on the main maternal fluids responsible for alteration of the primary immune response against E. coli showed that ovarian fluid increased phagocytosis at 48 h post-injection. These results indicated that the enhanced degradation of E. coli in parasitized pupae resulted mainly from the elevated bactericidal activity without observing the increased transcripts of target AMPs. This study contributes to a better understanding of the mechanisms involved in the immune responses of a parasitized host to bacterial infections.

scholarly journals Antimicrobial Interventions to Reduce Shiga Toxin-Producing Escherichia coli (STEC) Surrogate Populations on Beef Striploins Intended for Blade Tenderization

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
C. L. Thomas ◽  
H. Thippareddi ◽  
M. Rigdon ◽  
S. Kumar ◽  
R. W. McKee ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Sodium Dodecyl ◽  
Antimicrobial Treatment ◽  
Sodium Chlorite ◽  
Beef Industry ◽  
Anterior Portion ◽  
E Coli ◽  
Group Data ◽  
Blade Tenderization ◽  
Antimicrobial Interventions

ObjectivesBlade tenderization (BT) is used in the beef industry to improve tenderness of steaks prepared from subprimals but can translocate surface pathogens to the interior of meat. Application of antimicrobial solutions on the surface of subprimals prior to blade tenderization can reduce the risk of translocation of surface microorganisms. The objectives of this research were: 1) evaluate the efficacy of antimicrobial interventions applied to inoculated (surrogate Escherichia coli) beef striploins prior to blade tenderization; and 2) examine the transfer of E. coli from inoculated striploins to subsequent non-inoculated subprimals.Materials and MethodsThe anterior portion of whole muscle beef striploins (30.48 cm) were inoculated (lean side) across a 10 cm band with an approximately 8.00 log CFU/mL cocktail containing non-pathogenic, rifampicin-resistant surrogate STEC strains (BAA-1427, BAA-1428, BAA-1429, BAA-1430, and BAA-1431). The inoculated striploins were sprayed with (1) levulinic acid (5.0%) + sodium dodecyl sulfate (0.50%) (LVA+SDS), (2) peroxyacetic acid (2000 ppm; PAA; FCN 1666), (3) acidified sodium chlorite (1200 ppm; ASC), or (4) lactic acid (4.5%; LA) by passing through a spray cabinet and blade tenderized, along with an inoculated, non-sprayed control (CON). To evaluate the potential for cross-contamination of subsequent subprimals, an inoculated striploin (for each treatment) was blade tenderized followed by a non-inoculated beef striploin. For each striploin, surface and subsurface samples (2.54 cm wide) were collected from three different locations including the anterior, middle, and posterior end of each striploin. A total of 30 striploins across three replications were randomly assigned to treatment stratification. Sponge samples were also collected from the blade tenderizer (plate of the blade unit and blades) after each treatment group. Data were analyzed using Proc Mixed (SAS Inst., v.9.4; Cary, NC) as a completely randomized split-plot design. Microbial counts for all samples were log transformed and then analyzed for the main effects of antimicrobial treatment, location (anterior to posterior and surface or interior), and their interaction. Differences were considered significant at α ≤ 0.05.ResultsPAA was more effective in reducing E. coli populations (1.80 log CFU/g; P ≤ 0.05) and had lowest recovery of the microorganism from the striploin subsurface compared to other treatments, followed by LVA+SDS (1.00 log CFU/g). E. coli populations gradually decreased (P ≤ 0.05) on the surface and subsurface as sampling moved anterior to posterior. However, E. coli populations were similar (P > 0.05) on the posterior end of inoculated striploins and the anterior end of the subsequent, non-inoculated striploins, indicating transfer of microorganisms from one striploin to the following striploin. E. coli populations of 3.03 log CFU/cm2 and 2.47 log CFU/cm2 were recovered from the plate of the blade unit and the blades of the blade tenderizer. E. coli populations recovered from the plastic plate (3.46 log CFU/cm2) and blades (2.87 log CFU/cm2) of the blade tenderizer were the similar (P > 0.05) for all treatment groups except for PAA (1.41 log CFU/cm2 and 0.97 log CFU/cm2, respectively).ConclusionThese results showed that PAA and LVA+SDS can be used to improve the safety of blade tenderized beef.

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