scholarly journals Antibacterial Activity of Synthetic Cationic Iron Porphyrins

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 972
Author(s):  
Artak Tovmasyan ◽  
Ines Batinic-Haberle ◽  
Ludmil Benov

Widespread antibiotic resistance demands new strategies for fighting infections. Porphyrin-based compounds were long ago introduced as photosensitizers for photodynamic therapy, but light-independent antimicrobial activity of such compounds has not been systematically explored. The results of this study demonstrate that synthetic cationic amphiphilic iron N-alkylpyridylporphyrins exert strong bactericidal action at concentrations as low as 5 μM. Iron porphyrin, FeTnHex-2-PyP, which is well tolerated by laboratory animals, efficiently killed Gram-negative and Gram-positive microorganisms. Its bactericidal activity was oxygen-independent and was controlled by the lipophilicity and accumulation of the compound in bacterial cells. Such behavior is in contrast with the anionic gallium protoporphyrin IX, whose efficacy depends on cellular heme uptake systems. Under aerobic conditions, however, the activity of FeTnHex-2-PyP was limited by its destruction due to redox-cycling. Neither iron released from the Fe-porphyrin nor other decomposition products were the cause of the bactericidal activity. FeTnHex-2-PyP was as efficient against antibiotic-sensitive E. coli and S. aureus as against their antibiotic-resistant counterparts. Our data demonstrate that development of amphiphilic, positively charged metalloporphyrins might be a promising approach in the introduction of new weapons against antibiotic-resistant strains.

Author(s):  
О.В. Шамова ◽  
М.С. Жаркова ◽  
П.М. Копейкин ◽  
Д.С. Орлов ◽  
Е.А. Корнева

Антимикробные пептиды (АМП) системы врожденного иммунитета - соединения, играющие важную роль в патогенезе инфекционных заболеваний, так как обладают свойством инактивировать широкий спектр патогенных бактерий, обеспечивая противомикробную защиту живых организмов. В настоящее время АМП рассматриваются как потенциальные соединения-корректоры инфекционной патологии, вызываемой антибиотикорезистентными бактериями (АБР). Цель данной работы состояла в изученим механизмов антибактериального действия трех пептидов, принадлежащих к семейству бактенецинов - ChBac3.4, ChBac5 и mini-ChBac7.5Nb. Эти химически синтезированные пептиды являются аналогами природных пролин-богатых АМП, обнаруженных в лейкоцитах домашней козы Capra hircus и проявляющих высокую антимикробную активность, в том числе и в отношении грамотрицательных АБР. Методы. Минимальные ингибирующие и минимальные бактерицидные концентрации пептидов (МИК и МБК) определяли методом серийных разведений в жидкой питательной среде с последующим высевом на плотную питательную среду. Эффекты пептидов на проницаемость цитоплазматической мембраны бактерий для хромогенного маркера исследовали с использованием генетически модифицированного штамма Escherichia coli ML35p. Действие бактенецинов на метаболическую активность бактерий изучали с применением маркера резазурина. Результаты. Показано, что все исследованные пептиды проявляют высокую антимикробную активность в отношении Escherichia coli ML35p и антибиотикоустойчивых штаммов Escherichia coli ESBL и Acinetobacter baumannii in vitro, но их действие на бактериальные клетки разное. Использован комплекс методик, позволяющих наблюдать в режиме реального времени динамику действия бактенецинов в различных концентрациях (включая их МИК и МБК) на барьерную функцию цитоплазматической мембраны и на интенсивность метаболизма бактериальных клеток, что дало возможность выявить различия в характере воздействия бактенецинов, отличающихся по структуре молекулы, на исследуемые микроорганизмы. Установлено, что действие каждого из трех исследованных бактенецинов в бактерицидных концентрациях отличается по эффективности нарушения целостности бактериальных мембран и в скорости подавления метаболизма клеток. Заключение. Полученная информация дополнит существующие фундаментальные представления о механизмах действия пролин-богатых пептидов врожденного иммунитета, а также послужит основой для биотехнологических исследований, направленных на разработку на базе этих соединений новых антибиотических препаратов для коррекции инфекционных заболеваний, вызываемых АБР и являющимися причинами тяжелых внутрибольничных инфекций. Antimicrobial peptides (AMPs) of the innate immunity are compounds that play an important role in pathogenesis of infectious diseases due to their ability to inactivate a broad array of pathogenic bacteria, thereby providing anti-microbial host defense. AMPs are currently considered promising compounds for treatment of infectious diseases caused by antibiotic-resistant bacteria. The aim of this study was to investigate molecular mechanisms of the antibacterial action of three peptides from the bactenecin family, ChBac3.4, ChBac5, and mini-ChBac7.5Nb. These chemically synthesized peptides are analogues of natural proline-rich AMPs previously discovered by the authors of the present study in leukocytes of the domestic goat, Capra hircus. These peptides exhibit a high antimicrobial activity, in particular, against antibiotic-resistant gram-negative bacteria. Methods. Minimum inhibitory and minimum bactericidal concentrations of the peptides (MIC and MBC) were determined using the broth microdilution assay followed by subculturing on agar plates. Effects of the AMPs on bacterial cytoplasmic membrane permeability for a chromogenic marker were explored using a genetically modified strain, Escherichia coli ML35p. The effect of bactenecins on bacterial metabolic activity was studied using a resazurin marker. Results. All the studied peptides showed a high in vitro antimicrobial activity against Escherichia coli ML35p and antibiotic-resistant strains, Escherichia coli ESBL and Acinetobacter baumannii, but differed in features of their action on bacterial cells. The used combination of techniques allowed the real-time monitoring of effects of bactenecin at different concentrations (including their MIC and MBC) on the cell membrane barrier function and metabolic activity of bacteria. The differences in effects of these three structurally different bactenecins on the studied microorganisms implied that these peptides at bactericidal concentrations differed in their capability for disintegrating bacterial cell membranes and rate of inhibiting bacterial metabolism. Conclusion. The obtained information will supplement the existing basic concepts on mechanisms involved in effects of proline-rich peptides of the innate immunity. This information will also stimulate biotechnological research aimed at development of new antibiotics for treatment of infectious diseases, such as severe in-hospital infections, caused by antibiotic-resistant strains.


2017 ◽  
Vol 13 (11) ◽  
pp. 2323-2327 ◽  
Author(s):  
Ying Ge ◽  
Ya-Jun Zhou ◽  
Ke-Wu Yang ◽  
Yi-Lin Zhang ◽  
Yang Xiang ◽  
...  

A UV-Vis approach is reported for activity assays and inhibition of β-lactamases in complex biological systems of living bacteria.


Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 811
Author(s):  
Md. Akil Hossain ◽  
Hae-Chul Park ◽  
Sung-Won Park ◽  
Seung-Chun Park ◽  
Min-Goo Seo ◽  
...  

Pathogenic Escherichia coli (E. coli)-associated infections are becoming difficult to treat because of the rapid emergence of antibiotic-resistant strains. Novel approaches are required to prevent the progression of resistance and to extend the lifespan of existing antibiotics. This study was designed to improve the effectiveness of traditional antibiotics against E. coli using a combination of the gallic acid (GA), hamamelitannin, epicatechin gallate, epigallocatechin, and epicatechin. The fractional inhibitory concentration index (FICI) of each of the phenolic compound-antibiotic combinations against E. coli was ascertained. Considering the clinical significance and FICI, two combinations (hamamelitannin-erythromycin and GA-ampicillin) were evaluated for their impact on certain virulence factors of E. coli. Finally, the effects of hamamelitannin and GA on Rattus norvegicus (IEC-6) cell viability were investigated. The FICIs of the antibacterial combinations against E. coli were 0.281–1.008. The GA-ampicillin and hamamelitannin-erythromycin combinations more effectively prohibited the growth, biofilm viability, and swim and swarm motilities of E. coli than individual antibiotics. The concentration of hamamelitannin and GA required to reduce viability by 50% (IC50) in IEC-6 cells was 988.54 μM and 564.55 μM, correspondingly. GA-ampicillin and hamamelitannin-erythromycin may be potent combinations and promising candidates for eradicating pathogenic E. coli in humans and animals.


2019 ◽  
Vol 366 (8) ◽  
Author(s):  
Sophie Van Hamelsveld ◽  
Muyiwa E Adewale ◽  
Brigitta Kurenbach ◽  
William Godsoe ◽  
Jon S Harding ◽  
...  

Abstract Baseline studies are needed to identify environmental reservoirs of non-pathogenic but associating microbiota or pathogenic bacteria that are resistant to antibiotics and to inform safe use of freshwater ecosystems in urban and agricultural settings. Mesophilic bacteria and Escherichia coli were quantified and isolated from water and sediments of two rivers, one in an urban and one in an agricultural area near Christchurch, New Zealand. Resistance of E. coli to one or more of nine different antibiotics was determined. Additionally, selected strains were tested for conjugative transfer of resistances. Despite having similar concentrations of mesophilic bacteria and E. coli, the rivers differed in numbers of antibiotic-resistant E. coli isolates. Fully antibiotic-susceptible and -resistant strains coexist in the two freshwater ecosystems. This study was the first phase of antibiotic resistance profiling in an urban setting and an intensifying dairy agroecosystem. Antibiotic-resistant E. coli may pose different ingestion and contact risks than do susceptible E. coli. This difference cannot be seen in population counts alone. This is an important finding for human health assessments of freshwater systems, particularly where recreational uses occur downstream.


The Analyst ◽  
2020 ◽  
Vol 145 (22) ◽  
pp. 7320-7329
Author(s):  
Muhammad Asif ◽  
Fazli Rabbi Awan ◽  
Qaiser Mahmood Khan ◽  
Bongkot Ngamsom ◽  
Nicole Pamme

We investigate paper microfluidic devices for detection of pathogenic bacteria and their sensitivity towards β-lactamase and Extended Spectrum Beta Lactamases (ESBLs) in milk samples to enable appropriate prescription of antibiotics for mastitis.


1997 ◽  
Vol 60 (8) ◽  
pp. 1001-1005 ◽  
Author(s):  
MARIA A. TESSI ◽  
MARIA S. SALSI ◽  
MARIA I. CAFFER ◽  
MARIA A. MOGUILEVSKY

The antibiotic resistance profiles and transferable R factors of Salmonella and Escherichia coli isolates from 104 broiler carcasses taken from one processing plant were determined. Carcasses were sampled after immersion chilling. All samples were transported iced and immediately analyzed upon arrival to the laboratory. The resistance patterns of isolates to 12 antibiotics were determined (i.e., ampicillin, cephalothin, streptomycin, sulfisoxazole, trim-ethoprim-sulfamethoxazole, nalidixic acid, tetracycline, neomycin, chloramphenicol, gentamicin, colistin, and nitrofurantoin). Isolates resistant to one or more antibiotics were utilized as donors of resistance to completely antibiotic-sensitive strains, an E. coli K-12, F−, J5, azide-resistant strain and a Salmonella serovar Enteritidis. Transfer of the different R plasmids was confirmed by the determination of the resistance patterns of the transconjugants. Of the 93 Salmonella and 71 E. coli strains isolated from these samples, the largest numbers were resistant to tetracycline (52.7% and 49.3%), sulfisoxazole (45.2% and 42.3%), and streptomycin (37.6% and 39.4%). Large percentages of the Salmonella (33.3%) and the E. coli (30.0%) strains transferred all or part of their resistance to E. coli K-12 in mixed cultures. Great variation was observed between different strains in the frequency at which they transferred resistance. Resistance to tetracycline, sulfisoxazole, and streptomycin was found to be conferred by 31.7%, 29.8%, and 21.6% of the 19 R factors identified. No transfer of resistance to nalidixic acid, gentamicin, cephalothin, nitrofurantoin, and chloramphenicol was detected. When 30 antibiotic-resistant E. coli strains were cultured with a sensitive strain of Salmonella serovar Enteritidis,7 (23.3%) of the resistant strains were found capable of transferring R factors. Only 2 (6.7%) of the resistant strains could transfer R factors and unusual β-galactosidase activity.


Planta Medica ◽  
2019 ◽  
Vol 85 (16) ◽  
pp. 1253-1262 ◽  
Author(s):  
Matthew J. Cheesman ◽  
Alan White ◽  
Ben Matthews ◽  
Ian E. Cock

AbstractThe development of multiple antibiotic–resistant bacteria has vastly depleted our repertoire of effective antibiotic chemotherapies. The development of multi-β-lactam-resistant strains are particularly concerning due to our previous reliance on this class of antibiotics because of their initial efficacy and broad-spectrum activity. With increases in extended-spectrum β-lactam-resistance and an expanded resistance to other classes of antibiotics, there is an urgent need for the development of effective new antibiotic therapies. Terminalia ferdinandiana is an endemic Australian plant known for its high antioxidant and tannin contents. T. ferdinandiana fruit and leaf extracts have strong antibacterial activity against a wide variety of bacterial pathogens. However, T. ferdinandiana extracts have not been tested against ESBL and MRSA antibiotic-resistant pathogens. An objective of this study was to screen T. ferdinandiana fruit and leaf extracts for bacterial growth inhibitory activity by disc diffusion assay against β-lactam-sensitive and -resistant E. coli strains and against methicillin-sensitive and -resistant S. aureus. The minimum inhibitory concentration (MIC) was quantified by liquid dilution techniques. The fruit methanolic extract, as well as the methanolic, aqueous, and ethyl acetate leaf extracts strongly inhibited the growth of the MRSA, with MICs as low as 223 µg/mL. In contrast, the extracts were ineffective inhibitors of ESBL growth. Metabolomic fingerprint analysis identified a diversity and relative abundance of tannins, flavonoids, and terpenoids, several of which have been reported to inhibit MRSA growth in isolation. All extracts were nontoxic in the Artemia nauplii and HDF toxicity assays, further indicating their potential for medicinal use.


1998 ◽  
Vol 61 (10) ◽  
pp. 1390-1395 ◽  
Author(s):  
JOHN A. LOPES

Acid anionic sanitizers for treatment of fruits and vegetables were prepared using ingredients generally recognized as safe by the U.S. Food and Drug Administration or anionic surfactants and organic acid food additives. They met the regulatory definition as sanitizers by showing bactericidal efficacy of 99.999% in 30 s against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 11229. These sanitizers showed a broad spectrum of microbicidal activity against both gram-positive and gram-negative bacteria. Antibiotic-sensitive and resistant strains of Listeria monocytogenes and Salmonella typhimurium were equally susceptible to these sanitizers. The acid anionic sanitizers showed microbicidal efficacy equal to that of hypochlorite against Aeromonas hydrophila, E. coli O157:H7, L. monocytogenes, Pseudomonas aeruginosa, S. typhimurium, and S. aureus. Unlike most other sanitizers, these agents do not covalently react with organic components of food; unlike cationic agents, they do not leave residues. The acid anionic sanitizers are prepared using stable, biodegradable, and nontoxic ingredients. Rapid microbicidal activity and the ease of storage, transportation, and use make these sanitizers an attractive alternative to hypochlorite for sanitizing fruits and vegetables.


1999 ◽  
Vol 67 (4) ◽  
pp. 2005-2009 ◽  
Author(s):  
Monisha G. Scott ◽  
Hong Yan ◽  
Robert E. W. Hancock

ABSTRACT A series of α-helical cationic antimicrobial peptide variants with small amino acid changes was designed. Alterations in the charge, hydrophobicity, or length of the variant peptides did not improve the antimicrobial activity, and there was no statistically significant correlation between any of these factors and the MIC forPseudomonas aeruginosa, Escherichia coli, orSalmonella typhimurium. Individual peptides demonstrated synergy with conventional antibiotics against antibiotic-resistant strains of P. aeruginosa. The peptides varied considerably in the ability to bind E. coli O111:B4 lipopolysaccharide (LPS), and this correlated significantly with their antimicrobial activity and ability to block LPS-stimulated tumor necrosis factor and interleukin-6 production. In general, the peptides studied here demonstrated a broad range of activities, including antimicrobial, antiendotoxin, and enhancer activities.


Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 440 ◽  
Author(s):  
Nataliia P. Antonova ◽  
Daria V. Vasina ◽  
Evgeny O. Rubalsky ◽  
Mikhail V. Fursov ◽  
Alina S. Savinova ◽  
...  

The use of recombinant endolysins is a promising approach for antimicrobial therapy capable of counteracting the spread of antibiotic-resistant strains. To obtain the necessary biotechnological product, diverse peptide tags are often fused to the endolysin sequence to simplify enzyme purification, improve its ability to permeabilize the bacterial outer membrane, etc. We compared the effects of two different types of protein modifications on endolysin LysECD7 bactericidal activity in vitro and demonstrated that it is significantly modulated by specific permeabilizing antimicrobial peptides, as well as by widely used histidine tags. Thus, the tags selected for the study of endolysins and during the development of biotechnological preparations should be used with the appropriate precautions to minimize false conclusions about endolysin properties. Further, modifications of LysECD7 allowed us to obtain a lytic enzyme that was largely devoid of the disadvantages of the native protein and was active over the spectra of conditions, with high in vitro bactericidal activity not only against Gram-negative, but also against Gram-positive, bacteria. This opens up the possibility of developing effective antimicrobials based on N-terminus sheep myeloid peptide of 29 amino acids (SMAP)-modified LysECD7 that can be highly active not only during topical treatment but also for systemic applications in the bloodstream and tissues.


Sign in / Sign up

Export Citation Format

Share Document