scholarly journals The Trp-rich Antimicrobial Amphiphiles With Intramolecular Aromatic Interactions for the Treatment of Bacterial Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihua Wang ◽  
Qiuke Li ◽  
Jinze Li ◽  
Jiawei Li ◽  
Lu Shang ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Design Strategy ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Infection Group ◽  
Bacterial Colony ◽  
Aromatic Interactions ◽  
Cytokine Levels ◽  
Penetration Mechanism ◽  
Antimicrobial Performance

Antibiotic resistance is emerging as a hot issue with the abuse and overuse of antibiotics, and the shortage of effective antimicrobial agents against multidrug resistant bacteria creates a huge problem to treat the threatening nosocomial skin and soft tissue infection. Antimicrobial peptides (AMPs) exhibite enormous potential as one of the most promising candidates of antibiotic to fight against pathogenic infections because of its unique membrane penetration mechanism to kill pathogens, whereas the clinical application of AMPs still faces the challenges of production cost, stability, safety, and design strategy. Herein, a series of Trp-rich peptides was designed following the principle of paired Trp plated at the ith and ith+4 position on the backbone of peptides, based on the template (VKKX)4, where X represents W, A, or L, to study the effect of intramolecular aromatic interactions on the bioactivity of AMPs. Through comparing the antimicrobial performance, hemolysis, cytotoxicity, and stability, VW5 which is equipped with the characters of direct antimicrobial efficacy (GM=1.68μM) and physical destruction of bacterial membrane (SEM and electron microscopy) stood out from the engineering peptides. VW5 also performed well in mice models, which could significantly decrease the bacterial colony (VW5 vs infection group, 12.72±2.26 vs 5.52±2.01×109CFU/abscess), the area of dermo-necrosis (VW5 vs infection group, 0.74±0.29 vs 1.86±0.98mm2) and the inflammation cytokine levels at the abscess site without causing toxicity to the skin. Overall, this study provides a strategy and template to diminish the randomness in the exploration and design of novel peptides.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

scholarly journals Antimicrobial and Antibiofilm Peptides

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 652 ◽  
Author(s):  
Angela Di Somma ◽  
Antonio Moretta ◽  
Carolina Canè ◽  
Arianna Cirillo ◽  
Angela Duilio
Keyword(s):  
Antimicrobial Peptides ◽  
Biofilm Formation ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiofilm Activity ◽  
Chronic Infections ◽  
Planktonic Bacteria ◽  
Hostile Environments

The increasing onset of multidrug-resistant bacteria has propelled microbiology research towards antimicrobial peptides as new possible antibiotics from natural sources. Antimicrobial peptides are short peptides endowed with a broad range of activity against both Gram-positive and Gram-negative bacteria and are less prone to trigger resistance. Besides their activity against planktonic bacteria, many antimicrobial peptides also show antibiofilm activity. Biofilms are ubiquitous in nature, having the ability to adhere to virtually any surface, either biotic or abiotic, including medical devices, causing chronic infections that are difficult to eradicate. The biofilm matrix protects bacteria from hostile environments, thus contributing to the bacterial resistance to antimicrobial agents. Biofilms are very difficult to treat, with options restricted to the use of large doses of antibiotics or the removal of the infected device. Antimicrobial peptides could represent good candidates to develop new antibiofilm drugs as they can act at different stages of biofilm formation, on disparate molecular targets and with various mechanisms of action. These include inhibition of biofilm formation and adhesion, downregulation of quorum sensing factors, and disruption of the pre-formed biofilm. This review focuses on the proprieties of antimicrobial and antibiofilm peptides, with a particular emphasis on their mechanism of action, reporting several examples of peptides that over time have been shown to have activity against biofilm.

scholarly journals Membrane Perturbation Action Mode and Structure-Activity Relationships of Protonectin, a Novel Antimicrobial Peptide from the Venom of the Neotropical Social Wasp Agelaia pallipes pallipes

2013 ◽  
Vol 57 (10) ◽  
pp. 4632-4639 ◽  
Author(s):  
Kairong Wang ◽  
Wen Dang ◽  
Jiexi Yan ◽  
Ru Chen ◽  
Xin Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Social Wasp ◽  
Multidrug Resistant ◽  
Structural Features ◽  
Helical Conformation ◽  
Resistant Bacteria ◽  
Content Type ◽  
Natural Analog ◽  
Action Mode

ABSTRACTWith the extensive use of antibiotics, multidrug-resistant bacteria emerge frequently. New antimicrobial agents with novel modes of action are urgently needed. It is now widely accepted that antimicrobial peptides (AMPs) could be promising alternatives to conventional antibiotics. In this study, we aimed to study the antimicrobial activity and mechanism of action of protonectin, a cationic peptide from the venom of the neotropical social waspAgelaia pallipes pallipes. We demonstrated that protonectin exhibits potent antimicrobial activity against a spectrum of bacteria, including multidrug-resistant strains. To further understand this mechanism, the structural features of protonectin and its analogs were studied by circular dichroism (CD). The CD spectra demonstrated that protonectin and its natural analog polybia-CP formed a typical α-helical conformation in the membrane-mimicking environment, while its proline-substituted analog had much lower or even no α-helix conformation. Molecular dynamics simulations indicated that the α-helical conformation in the membrane is required for the exhibition of antibacterial activity. In conclusion, protonectin exhibits potent antimicrobial activity by disruption of the integrity of the bacterial membrane, and its α-helical confirmation in the membrane is essential for this action.

scholarly journals Emergence of high multidrug-resistant Escherichia coli isolates from neonates with infection

2020 ◽  
Author(s):  
Dan Wu ◽  
Yijun Ding ◽  
Jinjing Zhang ◽  
Kaihu Yao ◽  
Wei Gao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistance ◽  
Clavulanic Acid ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
E Coli ◽  
Mueller Hinton ◽  
Mueller Hinton Agar ◽  
Amoxicillin Clavulanic Acid

Abstract Background Escherichia coli (E.coli) rank one of the most common pathogens that can cause neonatal infections. The emergence of antibiotic-resistant bacteria is a major cause of treatment failure in newborn with infection. The purpose of this study was to describe the antibiotic resistance and multidrug-resistance of E.coli isolated from neonates with infection.Methods The antimicrobial susceptibility testing of the E. coli strains to selected antibiotics was assessed with the E-test technique on the Mueller-Hinton agar. The antimicrobials tests were included ceftazidime, cefuroxime, cefatriaxone, amoxicillin, amoxicillin-clavulanic acid, cefoperazone - sulbactam, meropenem, gentamicin, ciprofloxacin and sulfonamides. The minimal inhibitory concerntration (MIC) values of the antimicrobial agents selected for this study was determined by an agar dilution technique on Mueller-Hinton agar according to the Clinical and Laboratory Standards Institute recommendations. Results A total of 100 E. coli strains was isolated from phlegm (n = 78), blood (n = 10), cerebrospinal fluid (n = 5), and umbilical discharge (n = 7) of neonates hospitalized at Beijing Children’s Hospital. The highest resistance rate of E.coli was found in amoxicillin at 85%, followed by cefuroxime 65%, and cefatriaxone 60%, respectively. 6% and 5% of all isolates were resistant to amoxicillin/clavulanic acid and cefoperazone -sulbactam merely. The resistance rates to ceftazidime, gentamicin, ciprofloxacin and sulfonamides were 31%, 20%, 33%, 47%, respectively. All the isolates were susceptible to meropenem. Multidrug resistance was defined in E.coli as resistance to at least three antibiotic families. About 26% (26/100) of all the E.coli isolates were multidrug-resistant. The detection rate of ESBL-Producing E. coli was 55%. The rate in E. coli isolates from phlegm was higher than aseptic humoral. The difference was statistically significant (P < 0.05). It is worth noting that the majority of the isolates were also resistant to non-β-lactam antimicrobial agents, but the resistant rates were significantly lower than extended-spectrum β-lactamases.Conclusions: Multi-drug-resistant E.coli has become a thorny problem in clinical treatment. It is necessary to monitor E. coli resistance.

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 Bacteriocins, Antimicrobial Peptides from Bacterial Origin: Overview of Their Biology and Their Impact against Multidrug-Resistant Bacteria

2020 ◽  
Vol 8 (5) ◽  
pp. 639 ◽  
Author(s):  
Alexis Simons ◽  
Kamel Alhanout ◽  
Raphaël E. Duval
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Further Development

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.

scholarly journals 611. Fosfomycin Resistance of Multidrug-Resistant Escherichia coli and Mechanisms of Fosfomycin Resistance

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S285-S285
Author(s):  
Hyeri Seok ◽  
Ji Hoon Jeon ◽  
Hee Kyoung Choi ◽  
Won Suk Choi ◽  
Dae Won Park ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Coli Strain ◽  
Resistant Bacteria ◽  
E Coli ◽  
Broth Microdilution Method ◽  
Fosfomycin Resistance

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.

scholarly journals Antimicrobial O-Alkyl Derivatives of Naringenin and Their Oximes Against Multidrug-Resistant Bacteria

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3642 ◽  
Author(s):  
Anna Duda-Madej ◽  
Joanna Kozłowska ◽  
Paweł Krzyżek ◽  
Mirosław Anioł ◽  
Alicja Seniuk ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Quantitative Measure ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Beta Lactam ◽  
Multidrug Resistant Bacteria ◽  
Alkyl Derivatives ◽  
Vancomycin Resistant ◽  
Derivatives Of

New antimicrobial agents are needed to address infections caused by multidrug-resistant bacteria. Here, we are reporting novel O-alkyl derivatives of naringenin and their oximes, including novel compounds with a naringenin core and O-hexyl chains, showing activity against clinical strains of clarithromycin-resistant Helicobacter pylori, vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, and beta-lactam-resistant Acinetobacter baumannii and Klebsiella pneumoniae. The minimum inhibitory concentrations (MICs), which provide a quantitative measure of antimicrobial activity, were in the low microgram range for the selected compounds. Checkerboard assays for the most active compounds in combination with antibiotics revealed interactions that varied from synergistic to neutral.

scholarly journals A Review of Superbug: A Global Threat in Health Care System

2018 ◽  
Vol 4 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Bhuiyan Mohammad Mahtab Uddin ◽  
Md Abdullah Yusuf ◽  
Zubair Ahmed Ratan
Keyword(s):  
Public Health ◽  
Health Problem ◽  
Antimicrobial Agents ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Major Public Health Problem ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Hospital Acquired

The rapid spread and dissemination of the multidrug-resistant bacteria worldwide represents a major public health problem. The development of antibiotics decreased the mortality among the human and animals leading to a better life expectancy. But the injudicious use of antimicrobials and selection pressure the microbes have developed resistance which became more prominent during last few decades. With the evolution of Methicilin-resistant Staphylococcus aureus (MRSA), Hospital-acquired MRSA, Communityacquired MRSA and MDR TB (Multidrug resistant tuberculosis) challenge for the clinicians have increased to a greater extent. The global emergence and dissemination of acquired carbapenemases among gram negative bacteria are considered a major public health problem. Gram-negative bacteria, most notably Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, are among the most important causes of serious hospital-acquired and community-onset bacterial infections in humans, and resistance to antimicrobial agents in these bacteria has become an increasingly relevant problem. Recent development in nanotechnology based drug delivery system may prove to be solution for combating these resistant bacteria. However policies and regulations for antibiotic use should be formulated to control the further development of resistance among the microbes.Bangladesh Journal of Infectious Diseases 2017;4(1):25-28

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