Antibacterial activity and action target of phenyllactic acid against Staphylococcus aureus and its application in skim milk and cheese

Phenyllactic acid (PLA) has been demonstrated to possess antibacterial activity and capacity to prolong food shelf life. However, studies on the performance of PLA in inhibiting Staphylococcus aureus and its effectiveness when applied to dairy products are largely lacking. Here, antibacterial activity (planktonic and biofilm states) of PLA against S. aureus CICC10145 (S. aureus_45) were investigated. The results showed that PLA inhibited growth of S. aureus_45 and formation of S. aureus_45 biofilm. Next, the antibacterial action target of PLA was uncovered from both physiological and phenotypic perspectives. The results showed that PLA decreased cell metabolic activity and cell viability, damaged cell membrane integrity, triggered leakage of intracellular contents (DNA, proteins, and ATP), and caused oxidative stress damage and morphological deformation of S. aureus_45. In practical application, the antibacterial activity of PLA against S. aureus_45 cells was further confirmed in skim milk and cheese as dairy food models, and the antibacterial effects can be adequately maintained during storage for 21 d, at least at 4°C. These findings suggested that PLA could be a potential candidate for controlling S. aureus outgrowth in dairy foods.     

Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery

Aminoacyl-tRNA synthetases (aaRSs) catalyze the esterification of tRNA with a cognate amino acid and are essential enzymes in all three kingdoms of life. Due to their important role in the translation of the genetic code, aaRSs have been recognized as suitable targets for the development of small molecule anti-infectives. In this review, following a concise discussion of aaRS catalytic and proof-reading activities, the various inhibitory mechanisms of reported natural and synthetic aaRS inhibitors are discussed. Using the expanding repository of ligand-bound X-ray crystal structures, we classified these compounds based on their binding sites, focusing on their ability to compete with the association of one, or more of the canonical aaRS substrates. In parallel, we examined the determinants of species-selectivity and discuss potential resistance mechanisms of some of the inhibitor classes. Combined, this structural perspective highlights the opportunities for further exploration of the aaRS enzyme family as antimicrobial targets.     

Pyrazole-Thiazole Core-Containing Analogs Exhibit Adjunctive Activity with Meropenem against Carbapenem-Resistant Enterobacteriaceae (CRE)

Pyrazole-thiazole core-containing compound KP-40 and 20 novel derivatives were designed and synthesized through traditional SAR analysis. These molecules displayed adjunctive activity with meropenem against Gram-negative bacteria evidenced by a range of fractional inhibitory concentration (FIC=0.5–0.25) and minimum adjunctive concentration (MAC=128–32 μM) values. Of this series of molecules, four compounds displayed notable adjunctive potential, with FIC and MAC values of 0.25 and 32 μM, respectively. Moreover, the solubility of these compounds was improved to an acceptable range. Further analysis using our “in house” permeation and efflux multi parameter optimization (PEMPO) algorithm revealed key physicochemical properties that may be critical for the development of active Gram-negative antibacterials. Taking PEMPO scores into consideration prior to executing synthesis of analogs may be a simple, yet rapid and effective strategy that can be used in conjunction with traditional SAR approaches to aid in the design of potent Gram-negative antibacterials.     

Remarkable Antibacterial Activity of Reduced Graphene Oxide Functionalized by Copper Ions

Despite long-term efforts for exploring antibacterial agents or drugs, potentiating antibacterial activity and meanwhile minimizing toxicity to the environment remains a challenge. Here, it is experimentally shown that the functionality of reduced graphene oxide (rGO) through copper ions displays selective antibacterial activity that is significantly stronger than that of rGO itself and no toxicity to mammalian cells. Remarkably, this antibacterial activity is two-orders-of-magnitude greater than the activity of its surrounding copper ions. It is demonstrated that rGO is functionalized through the cation–π interaction to massively adsorb copper ions to form a rGO–copper composite and result in an extremely low concentration level of surrounding copper ions (less than ≈0.5 µm ). These copper ions on rGO are positively charged and strongly interact with negatively charged bacterial cells to selectively achieve antibacterial activity, while rGO exhibits the functionality to not only actuate rapid delivery of copper ions and massive assembly onto bacterial cells but also result in the valence shift in the copper ions from Cu²⁺ into Cu⁺, which greatly enhances the antibacterial activity. Notably, this rGO functionality through cation–π interaction with copper ions can similarly achieve algaecidal activity but does not exert cytotoxicity against neutrally charged mammalian cells.     

Peptide-Mimicking Poly(2-oxazoline)s Displaying Potent Antimicrobial Properties

Poly(2-oxazoline)s have excellent biocompatibility and have been used as FDA-approved indirect food additives. The inert property of the hydrophilic poly(2-oxazoline)s suggests them as promising substitutes for poly(ethylene glycol) (PEG) in various applications such as anti-biofouling agents. It was recently reported that poly(2-oxazoline)s themselves have antimicrobial properties as synthetic mimics of host defense peptides. These studies revealed the bioactive properties of poly(2-oxazoline)s as a new class of functional peptide mimics, by mimicking host defense peptides to display potent and selective antimicrobial activities against methicillin-resistant Staphylococcus aureus both in vitro and in vivo, without concerns about antimicrobial resistance. The high structural diversity, facile synthesis, and potent and tunable antimicrobial properties underscore the great potential of poly(2-oxazoline)s as a class of novel antimicrobial agents in dealing with drug-resistant microbial infections and antimicrobial resistance.     

Studying the effect of particle size on the antibacterial activity of some N-nicotinyl phosphoric triamides

Using ultrasonic top-to-down method, nanoparticles of two N-nicotinyl phosphoric triamides: C₅H₄NC(O)NHP(O)R, R?=?4-CH₃-NC₅H₁₀ (1), (CH₃)₃CNH₂ (2) were prepared for the first time and characterized by ³¹P, ¹³C, ¹H NMR, FTIR, scanning electron microscopy, energy dispersive X-ray. The average particle size of 1 and 2 were 60–70 and 40–50?nm, respectively, and the morphology was spherical for 1 and rod for 2. Solid state (powder) antibacterial effect of these compounds and two other similar reported ones, in their macro- and nanosizes, were evaluated with colony counting method on one Gram-positive (Staphylococcus aureus) and one Gram-negative (Escherichia coli) bacteria in Brain–Heart infusion culture medium. Results showed that all the macro- and nanosized compounds, except macrosized 1, were antibacterial and all nanoscaled ones had stronger antibacterial activity than their macroscaled analogues. The most effect of the particle size was observed for 1: by decreasing the particle sizes, the antibacterial activity state of 1 was changed from inactive (for macro) to potent (for nano).     

Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.     

氧化壳聚糖改性抗菌蚕丝织物的制备及其性能

为获得持久抗菌的功能丝绸材料,采用硝酸、磷酸、亚硝酸钠体系将原料壳聚糖的C6位伯羟基选择性氧化为羧基制得水溶性氧化壳聚糖(OCS),使OCS的羧基与脱胶蚕丝织物(SFF)的氨基反应,得到氧化壳聚糖改性蚕丝织物(OCSMSF)。借助核磁共振仪、扫描电子显微镜、红外光谱仪、X射线衍射仪等手段表征了OCS与OCSMSF的化学结构,测试了OCSMSF的力学、吸湿、抗菌等性能。结果表明:酰胺反应已将氧化壳聚糖分子化学键合在SFF中,OCS改性蚕丝纤维的结晶度降低;在优化反应参数条件下,OCS接枝蚕丝织物的质量增加率达到9.17%,OCSMSF的强力略有减小,而吸湿性提高42.92%,OCSMSF对测试细菌的抑菌率大于94%,且抗菌耐洗涤性好,同时OCSMSF对仙人掌黄酮提取物有良好的缓释效果。     

抑菌纸对吐司保鲜作用

研究了抑菌纸对吐司保鲜作用的影响。将抑菌纸与PP薄薄膜结合得到纸塑复合材料来包装吐司，与单一的PP薄膜包装以及未采取包装的吐司对比质构、色差、水分活度、菌落总数、热焓值的差异。结果表明：采用纸塑复合材料包装的吐司相较于仅用PP薄膜包装以及未采取包装的吐司，其质构特性和色差的劣变变缓，水分活度有一定程度降低，菌落总数的增长得到有效抑制，热焓值的上升也得到延缓。该抑菌纸与PP薄膜结合得到的复合材料可避免直接向食品中添加防腐剂，并且能有效延长吐司的货架期。