Antimicrobial betalains

Betalains are nitrogen-containing plant pigments that can be red-violet (betacyanins) or yellow-orange (betaxanthins), currently employed as natural colourants in the food and cosmetic sectors. Betalains exhibit antimicrobial activity against a broad spectrum of microbes including multidrug-resistant bacteria, as well as single-species and dual-species biofilm-producing bacteria, which is highly significant given the current antimicrobial resistance issue reported by The World Health Organization. Research demonstrating antiviral activity against dengue virus, in silico studies including SARS-CoV-2, and anti-fungal effects of betalains highlight the diversity of their antimicrobial properties. Though limited in vivo studies have been conducted, antimalarial and anti-infective activities of betacyanin have been observed in living infection models. Cellular mechanisms of antimicrobial activity of betalains are yet unknown; however existing research has laid the framework for a potentially novel antimicrobial agent. This review covers an overview of betalains as antimicrobial agents and discussions to fully exploit their potential as therapeutic agents to treat infectious diseases.     

The chemistry and applications of antimicrobial polymers: a state-of-the-art review

Microbial infection remains one of the most serious complications in several areas, particularly in medical devices, drugs, health care and hygienic applications, water purification systems, hospital and dental surgery equipment, textiles, food packaging, and food storage. Antimicrobials gain interest from both academic research and industry due to their potential to provide quality and safety benefits to many materials. However, low molecular weight antimicrobial agents suffer from many disadvantages, such as toxicity to the environment and short-term antimicrobial ability. To overcome problems associated with the low molecular weight antimicrobial agents, antimicrobial functional groups can be introduced into polymer molecules. The use of antimicrobial polymers offers promise for enhancing the efficacy of some existing antimicrobial agents and minimizing the environmental problems accompanying conventional antimicrobial agents by reducing the residual toxicity of the agents, increasing their efficiency and selectivity, and prolonging the lifetime of the antimicrobial agents. Research concerning the development of antimicrobial polymers represents a great a challenge for both the academic world and industry. This article reviews the state of the art of antimicrobial polymers primarily since the last comprehensive review by one of the authors in 1996. In particular, it discusses the requirements of antimicrobial polymers, factors affecting the antimicrobial activities, methods of synthesizing antimicrobial polymers, major fields of applications, and future and perspectives in the field of antimicrobial polymers.     

A microcalorimetric comparison of the anti-Streptococcus mutans efficacy of plant extracts and antimicrobial agents in oral hygiene formulations

AIMS: This study aimed to evaluate the efficacy of 'natural' putative antimicrobial agents against Streptococcus mutans and to compare these with synthetic agents using the flow microcalorimeter. Streptococcus mutans is one of the oral pathogens responsible for dental caries. METHODS AND RESULTS: Traditional microbiological techniques are invasive and destructive unlike flow microcalorimetry. This rapid technique was used to continuously monitor the power output (bioactivity) of Strep. mutans with reproducibility, precision and accuracy. The antibacterial agents found in oral hygiene products and all the natural agents tested showed anti-Strep. mutans ability. CONCLUSION: In this study microcalorimetry identified agents that had a biological effect and quantified the rate of kill achieved enabling four broad categories of antimicrobial agent to be defined. SIGNIFICANCE AND IMPACT OF THE STUDY: Microcalorimetric data are a better indication of antimicrobial efficacy than merely determining concentrations at which an antimicrobial agent is bacteriostatic or bactericidal.     

肝病住院患者抗菌药物使用调查

目的了解肝病住院患者抗菌药物的使用情况。方法对62例肝病住院患者抗菌药物的应用进行调查。结果抗菌药物的使用率为25.81％;单用占75．00％;主要抗菌药物为哌拉西林、阿莫西林和头孢曲松;用药途径以静脉以及口服 静脉为主;以治疗性用药为主,预防用药在住院患者中的总使用率为4．84％;细菌标本送检率仅为6．25％。结论减少预防性用药,严格掌握抗菌药物的使用可降低抗菌药物的应用率;对于复数耐药菌感染应采取联合用药;提高细菌标本的送检率对于抗菌药物的合理应用十分重要;加强临床医师的抗菌药物知识更新和公众普及教育。     

Effect of new antimicrobial agents on the ecological balance of human microflora

The human normal microflora is relatively stable at each ecological habitat under normal circumstances and acts as a barrier against colonization by potentially pathogenic microorganisms and against overgrowth of already present opportunistic microorganisms. Administration of antimicrobial agents causes disturbances in the ecological balance between the host and the normal microflora. The risk of emergence and spread of resistant strains between patients and dissemination of resistant determinants between microorganisms is reduced if colonization resistance is not disturbed by antimicrobial agents. In this article, the potential ecological effects of administration of new antimicrobial agents on the intestinal and oropharyngeal microflora are summarized. The review is based on clinical studies published during the past 10 years.     

Antimicrobial and antioxidative activity of extracts and essential oils of Myrtus communis L.

Since synthetic antimicrobial agents and food additives can cause a number of adverse effects, there is a growing interest from consumers in ingredients from natural sources. Medicinal plants, such as Myrtus communis L. are a source of new compounds which can be used in both the food industry and for medical purposes, primarily as antimicrobial agents. In this review, the characteristics of myrtle essential oils and extracts are summarized, with particular attention to their chemical composition, biological activities and potential applications.     

Genes and mutations conferring antimicrobial resistance in Salmonella: an update

Resistance to various classes of antimicrobial agents has been encountered in many bacteria of medical and veterinary relevance. Particular attention has been paid to zoonotic bacteria such as Salmonella. Over the years, various studies have reported the presence of genes and mutations conferring resistance to antimicrobial agents in Salmonella isolates. This review is intended to provide an update on what is currently known about the genetic basis of antimicrobial resistance in Salmonella.     

The action of berry phenolics against human intestinal pathogens

Phenolic compounds present in berries selectively inhibit the growth of human gastrointestinal pathogens. Especially cranberry, cloudberry, raspberry, strawberry and bilberry possess clear antimicrobial effects against e.g. salmonella and staphylococcus. Complex phenolic polymers, such as ellagitannins, are strong antibacterial agents present in cloudberry, raspberry and strawberry. Berry phenolics seem to affect the growth of different bacterial species with different mechanisms. Adherence of bacteria to epithelial surfaces is a prerequisite for colonization and infection of many pathogens. Antimicrobial activity of berries may also be related to anti-adherence activity of the berries. Utilization of enzymes in berry processing increases the amount of phenolics and antimicrobial activity of the berry products. Antimicrobial berry compounds are likely to have many important applications in the future as natural antimicrobial agents for food industry as well as for medicine.     

Natural and hemi-synthetic pentacyclic triterpenes as antimicrobials and resistance modifying agents against <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>: a review

Staphylococcus aureus infections are considered as seriously problematic for human health and necessitate the development of new medicines and innovative antimicrobial strategies. Plant secondary metabolites have already demonstrated their potential as antibacterials when used alone but also in combination with other antimicrobial agents to potentiate their activity. Triterpenoids are widely distributed in the plant kingdom and known to have many beneficial effects, including anti-inflammatory, immunomodulatory, anti-proliferative, antimycotic, or antimicrobial activity. The aim of this paper is to review the activity of pentacyclic triterpenoids belonging to the ursane, oleanane, or lupane groups against Staphylococcus aureus. We summarize their activity as anti-staphylococcal compounds but also as resistance modifying agents when combined with common antibiotics.     

2003年至2007年大肠埃希菌的临床分离及耐药趋势分析

目的了解2003年至2007年大肠埃希菌在临床标本中的分离情况及其耐药趋势,为临床感染的预防和治疗提供参考资料。方法回顾分析2003年至2007年间所有标本中大肠埃希菌的分离率、标本和病区的分布构成情况以及对17种抗菌药物的耐药率。结果五年间大肠埃希菌的总分离率变化不明显,但其阳性分离率呈上升趋势,从2003年的5.02%增至2007年的6.26%;其在泌尿生殖道标本（尿液标本和尿道分泌物标本）的分离率最高（50.5%）,其次是呼吸道标本（36.66%）;病区分布以重症监护室最高（20.7%）,其次是普外科（18.3%）,所有内科病区（不含ICU）占46.6%;大肠埃希菌对12种抗菌药的耐药率大于50%,仅对其中5种的耐药率每年均低于50%。结论大肠埃希菌的临床总分离率没有明显变化,但阳性分离率有呈上升趋势,其对多数抗菌药物有较高的耐药性,所以感染的治疗应当依据抗菌药物的体外敏感试验。     

VirAB在单核细胞增生李斯特菌耐药性及生物被膜形成中的作用

【背景】单核细胞增生李斯特菌(Listeria monocytogenes,Lm)对一些临床常用抗生素、乳酸链球菌素(Nisin)等抗菌药物的敏感性下降,然而其背后的机制仍未完全阐明。【目的】调查转运蛋白VirAB在Lm对抗菌药物的耐药性及生物被膜形成中的作用。【方法】利用同源重组技术构建Lm基因缺失突变株,比较野生株和缺失株对抗菌药物的耐药性;利用微孔板法观测突变株生物被膜形成能力的变化;利用平板泳动法研究菌株的泳动能力。【结果】与野生株相比,virAB缺失突变株对头孢类抗生素、Nisin和溴化乙锭的敏感性增加;当培养基中分别添加亚致死浓度的苯扎氯铵、卡那霉素和四环素时,突变株均表现出不同程度的生长缺陷。缺失virAB后菌株形成生物被膜的能力下降。【结论】VirAB在Lm对头孢类等抗菌药物的耐药及生物被膜形成方面具有重要作用。     

抗菌肽结构改造与人工智能研发策略

抗菌肽是一类广泛存在于生物体内的小分子肽,参与构成生物体先天免疫,可以有效抵抗病原微生物的入侵。抗菌肽具有广谱抗菌活性,且不易产生耐药性等特点,在治疗感染性疾病方面具有独特的优势,有望成为理想的抗感染药物。然而,由于部分抗菌肽尚存在稳定性差、毒性高等问题,限制了抗菌肽的广泛应用。由于人工智能算法能有效合成具有高稳定性、低毒性的抗菌肽,在探索天然抗菌肽中展现了巨大的潜力,因此本文简述了抗菌肽的抗菌机制、结构改造以及利用机器学习和深度学习等人工智能算法进行新型抗菌肽研发的优化策略,以期为抗菌肽结构优化及研发提供新思路。     

A microcalorimetric comparison of the anti-Streptococcus mutans efficacy of plant extracts and antimicrobial agents in oral hygiene formulations

T. D. MORGAN, A. E. BEEZER, J. C. MITCHELL AND A. W. BUNCH. 2001 .
Aims: This study aimed to evaluate the efficacy of 'natural' putative antimicrobial agents against Streptococcus mutans and to compare these with synthetic agents using the flow microcalorimeter. Streptococcus mutans is one of the oral pathogens responsible for dental caries.
Methods and Results: Traditional microbiological techniques are invasive and destructive unlike flow microcalorimetry. This rapid technique was used to continuously monitor the power output (bioactivity) of Strep. mutans with reproducibility, precision and accuracy. The antibacterial agents found in oral hygiene products and all the natural agents tested showed anti- Strep. mutans ability.
Conclusions: In this study microcalorimetry identified agents that had a biological effect and quantified the rate of kill achieved enabling four broad categories of antimicrobial agent to be defined.
Significance and Impact of the Study: Microcalorimetric data are a better indication of antimicrobial efficacy than merely determining concentrations at which an antimicrobial agent is bacteriostatic or bactericidal.     

铁载体-抗生素耦合物:一种新型的抗菌制剂

随着细菌对抗生素耐药性的增强,寻找一种新型抗菌制剂越来越重要。细菌细胞外膜对药物分子的通透性降低是引起致病菌产生耐药性的一个重要因素,克服膜介导耐药性的方法之一是利用铁载体-抗生素耦合物。铁载体是细菌分泌的一种小分子铁离子螯合物,与铁离子螯合后被特定的外膜受体识别并转运至胞浆内供细菌利用。人工合成的铁载体-抗生素耦合物被特定外膜受体识别后主动转运跨过外膜进入胞质内。当铁载体-抗生素耦合物到达细胞质,它们通过释放药物杀死微生物,这可以阻止进一步获取铁离子,并且耦合物自身也可以作为一种抗菌剂。本文综述了铁载体-抗生素耦合物作为一种新型抗菌制剂的研究进展,有助于为进一步研发新型抗菌药物提供理论基础,对治疗耐药性细菌性疾病具有潜在的重要意义。     

Binding properties of antimicrobial agents to dipeptide terminal of lipid II using surface plasmon resonance

We developed a surface plasmon resonance (SPR) assay to estimate the interactions of antimicrobial agents with the dipeptide terminal of lipid II (d-alanyl-d-alanine) and its analogous dipeptides (l-alanyl-l-alanine and d-alanyl-d-lactate) as ligands. The established SPR method showed the reproducible immobilization of ligands on sensor chip and analysis of binding kinetics of antimicrobial agents to ligands. The ligand-immobilized chip could be used repeatedly for at least 200 times for the binding assay of antimicrobial agents, indicating that the ligand-immobilized chip is sufficiently robust for the analysis of binding kinetics. In this SPR system, the selective and specific binding characteristics of vancomycin and its analogs to the ligands were estimated and the kinetic parameters were calculated. The kinetic parameters revealed that one of the remarkable binding characteristics was the specific interaction of vancomycin to only the d-alanyl-d-alanine ligand. In addition, the kinetic binding data of SPR showed close correlation with the antimicrobial activity. The SPR data of other antimicrobial agents (e.g., teicoplanin) to the ligands showed correlation with the antimicrobial activity on the basis of the therapeutic mechanism. Our SPR method could be a valuable tool for predicting the binding characteristics of antimicrobial agents to the dipeptide terminal of lipid II.     

Sensitivity of environmental microorganisms to antimicrobial agents.

The sensitivity of different microorganisms, considered as typical representatives of the microflora of soil and water, was established to evaluate the influence of the nonmedical use of antimicrobial agents on bacterial ecology. Only seven strains, six chemoorganotrophs and one chemolithotroph, could be considered as relatively sensitive to the 21 antimicrobial compounds tested. The other 29 microorganisms may be regarded as resistant to most antimicrobial agents. Streptomyces were sensitive to high concentrations of active substances. Broad-spectrum antibiotics showed an effect on environmental bacteria similar to that on human pathogens. Cephalothin stimulated the growth of a Chlorella sp. From these experiments, it appears that spilled antimicrobial agents have little chance of causing an alteration in the microbial ecology.     

Bioactive berry compounds—novel tools against human pathogens

Berry fruits are rich sources of bioactive compounds, such as phenolics and organic acids, which have antimicrobial activities against human pathogens. Among different berries and berry phenolics, cranberry, cloudberry, raspberry, strawberry and bilberry especially possess clear antimicrobial effects against, e.g. Salmonella and Staphylococcus. Complex phenolic polymers, like ellagitannins, are strong antibacterial agents present in cloudberry and raspberry. Several mechanisms of action in the growth inhibition of bacteria are involved, such as destabilisation of cytoplasmic membrane, permeabilisation of plasma membrane, inhibition of extracellular microbial enzymes, direct actions on microbial metabolism and deprivation of the substrates required for microbial growth. Antimicrobial activity of berries may also be related to antiadherence of bacteria to epithelial cells, which is a prerequisite for colonisation and infection of many pathogens. Antimicrobial berry compounds may have important applications in the future as natural antimicrobial agents for food industry as well as for medicine. Some of the novel approaches are discussed.     

Potassium and tetraphenylphosphonium ion-selective electrodes for monitoring changes in the permeability of bacterial outer and cytoplasmic membranes

A tetraphenylphosphonium ion (TPP(+))-selective electrode, originally developed as a membrane potential indicator, is useful for measuring increases in the permeability of bacterial outer membranes induced by antimicrobial agents. The combination of this electrode with a potassium ion-selective electrode enabled us to determine changes in the permeability of bacterial outer and cytoplasmic membranes simultaneously. Outer membrane permeabilization induced by antimicrobial agents, chlorhexidine and polyhexamethylene biguanide (PHMB), as monitored with the TPP(+) electrode, correlated closely with the ability of the agents to release lipopolysaccharide (LPS) from the outer membrane.     

Antibiotic abuse: the testimony of medical students.

Surveys of the use of antimicrobial drugs on students during antimicrobial drugs on students during their first 15 months in medical or dental school indicate that they have been treated with these agents at least three times as frequently as seems reasonable, and that the tetracyclines, ampicillin, penicillin G and erythromycin are the chief drugs overused. Antimicrobiol therapy is frequently instituted for probable viral respiratory tract infections and without any attempt to establish a bacteriologic diagnosis. It is likely that anitmicrobiol agents are used more widely in treating the general public in Canada than in treating medical students. Improvements in the rational use of this important group of drugs could increase the quality and probably reduced the cost of medical care.     

Antimicrobial dyes and mechanosensitive channels

The search for new and effective antimicrobial agents has never been as important; however, since the discovery of antibiotics, exploring the antimicrobial activity of dyes has been forgotten. Antimicrobial dyes are an untapped resource and have the ability to potentially combat the spread of drug-resistant bacteria either alone or as antimicrobial adjuvants. The mechanosensitive ion channel of large conductance (MscL) is highly conserved and ubiquitous in bacterial species. There is evidence to suggest that at least one triphenylmethane dye acts through the highly conserved MscL channel and combining the two approaches of exploring the mechanism of action of other triphenylmethane dyes or antimicrobial dyes in general and the novel MscL target provides a new opportunity for further exploration.