Potent Antibiotics Research Articles

A comparative analysis of Asian medicinal herbs Catharanthus roseus and Vinca alba based on their antidiabetic, anticancer and turbidimetric antibiotic efficacies

Being on Northern Hemisphere, India is a geographically established country with a large variety of species variation in terms of animals and plants species. According to geographical location, the land barriers in north and the oceanic barriers in east and west region of India made the differences among medicinal plant species being isolated from different areas.To isolate the pharmaceutical values of those species for antidiabetic, anticancer and antibiotic potencies are essential for further drug establishments from Catharanthus roseus and .Turbidimetric Assay or Tube Assay method is used to determine antibiotic efficacy against Vinblastine (VLB) and Vincristine (VCR) Reference standards. Bradford assay is used to identify protein content against standard curve. Polysaccharide and Amino acid assay are used to evaluate unknown concentration of dextrose and glycine against known concentration. Presence of alkaloids are tested by Mayer’s test. Thin Layer Chromatography is used to assume presence of Amino acids rich in anticancer peptides.Both leaf and stem extracts of and are showing significant amount of polysaccharide content, strong protein content, presence of alkaloids, anticancer peptides, hypoglycemic or antidiabetic and antibiotic efficacies.The medicinal plant species and are well known to be helpful for the medical, biological, pharmacological and biochemical studies for human benefits. So, the desire of medicinal plant utility is a certain thing from the ancient era, till from “Ayurveda shastra” that intricates the therapeutic capability of and .

Highly Sensitive In Vivo Imaging of Bacterial Infections with a Hydrophilicity-Switching, Self-Immobilizing, Near-Infrared Fluorogenic β-Lactamase Probe Enriched within Bacteria.

The emergence of antibiotic resistance, particularly bacterial resistance to β-lactam antibiotics, the most widely prescribed therapeutic agents for infectious diseases, poses a significant threat to public health worldwide. The discovery of effective therapies against antibiotic-resistant pathogens has become an urgent need, necessitating innovative approaches to accelerate the identification and development of novel antibacterial agents. On the other hand, the expression of the β-lactam-hydrolyzing enzyme (β-lactamase), the major cause of bacterial resistance to β-lactam antibiotics, provides a distinctive opportunity to visualize bacterial infection, evaluate the efficacy of existing antibiotics, screen for novel antibacterial agents, and optimize drug dosing regimens in live animals. Herein, a hydrophilicity-switching, self-immobilizing, near-Infrared fluorogenic β-lactamase probe for the highly sensitive imaging of bacterial infection in live mice is reported. This probe, in addition to a significant increase in fluorescence upon selective hydrolysis by β-lactamases as conventional β-lactamase probes, also massively enriches within β-lactamase-expressing bacteria (over 1500-folds compared to the incubation medium), which renders excellent sensitivity in the imaging of bacterial infections in living animals. This agent has proven to enable the assessment of antibiotic therapeutic efficacy and potency of β-lactamase inhibitors in living animals in a non-invasive and much more convenient manner.

Optimization study and luminescence enhancement effect for the determination of moxifloxacin using some rare elements

Moxifloxacin is a potent fluoroquinolone antibiotic and a promising antibacterial drug that significantly reduces skin, pneumonia, and respiratory pathogens. Herein, sensitive fluorescent trivalent lanthanides are desired as a facile, rapid, and effective MOX detection technique using light and heavy rare earth elements, such as Eu3+ and Tb3+, respectively. This spectrofluorometric technique relies on the nonradiative intramolecular energy transfer from MOX to lanthanide ions in the presence of cooperative ligands, for instance, 2,2′-bipyridine, 1,10-phenanthroline, or ethylene diamine, and an anionic surfactant (sodium dodecyl benzene sulfonate SDBS). Optimal fluorescence parameters, for instance, λex, λem, pH, concentrations of MOX, Ln3+, SDBS, and coordinating ligands, were determined based on the extent of sensitization. Micellar-enhanced fluorescence was also studied. The fluorescence intensity of the quaternary MOX-Ln3+-SDBS-phen system dramatically increased with MOX concentrations ranging from 0.4 to 8 µg/mL, with a determination coefficient and detecting limit of 0.9977 and 0.0221 µg/mL, respectively. The emission quantum yields of all systems were calculated, and it was observed that MOX-Tb3+-phen-SDBS has the highest quantum yield (0.26). Furthermore, the performance of this precise technique for detecting MOX was confirmed in pharmaceutical tablets and human serum/urine samples. The satisfactory recoveries% and RSD were found from 99.25 to 100.5 % and 1.6 to 1.8 % in tablets and from 95.33 to 103.35 % with 0.7 to 2.9 % in human samples, respectively.

Pattern-Based Genome Mining Guides Discovery of the Antibiotic Indanopyrrole A from a Marine Streptomycete.

Terrestrial actinomycetes in the genus Streptomyces have long been recognized as prolific producers of small-molecule natural products, including many clinically important antibiotics and cytotoxic agents. Although Streptomyces can also be isolated from marine environments, their potential for natural product biosynthesis remains underexplored. The MAR4 clade of largely marine-derived Streptomyces has been a rich source of novel halogenated natural products of diverse structural classes. To further explore the biosynthetic potential of this group, we applied pattern-based genome mining, leading to the discovery of the first halogenated pyrroloketoindane natural products, indanopyrrole A (1) and B (2), and the bioinformatic linkage of these compounds to an orphan biosynthetic gene cluster (BCG) in 20 MAR4 genomes. Indanopyrrole A displays potent broad-spectrum antibiotic activity against clinically relevant pathogens. A comparison of the putative indanopyrrole BGC with that of the related compound indanomycin provides new insights into the terminal cyclization and offloading mechanisms in pyrroloketoindane biosynthesis. Broader searches of public databases reveal the rarity of this BGC while also highlighting opportunities for discovering additional compounds in this uncommon class.

Bioactive compounds from fermented Vernonia amygdalina leaf: Potent antibiotics against multidrug-resistant Escherichia coli and Salmonella typhi.

The online version contains supplementary material available at 10.1007/s40203-024-00277-2.

A generic cell-based biosensor converts bacterial infection signals into chemoattractants for immune cells

Bacterial infections are a major challenge to human health. Although various potent antibiotics have emerged in the last decades, current challenges arise from an increasing number of multi-drug-resistant species. Infections associated with implants represent a particular challenge since they are usually diagnosed at an advanced state, and are difficult to treat with antibiotics due to the formation of protecting biofilms. In this study, we designed and explored a synthetic biology-inspired, cell-based bio-sensor/actor for the detection and counteraction of bacterial infections. The system is generic as it senses diverse types of infections and acts by enhancement of the endogenous immune system. The strategy is based on genetically engineered sensor/actor cells that can sense type I interferons (IFNs), which are released by immune cells at the early stages of infections. IFN signalling activates a synthetic circuit to induce reporter genes with a sensitivity of only 5 pg/ml of IFN and leads to a therapeutic protein output of 100ng/ml, resulting in theranostic cells that visualize and fight infections. Robustness and resilience were achieved by the implementation of a positive feedback loop. We show that diverse gram-positive and gram-negative implant-associated pathogenic bacteria activate the cascade in co-culture systems in a dose-dependent manner. Finally, we show that this system can be used to secrete chemoattractants facilitating the infiltration of immune cells in response to bacterial triggers. Together, the system is not only universal to bacterial infections but at the same time hypersensitive allowing the sensing of infections at initial stages.

A Cell-Based Screening Assay for rRNA-Targeted Drug Discovery.

Worldwide, bacterial antibiotic resistance continues to outpace the level of drug development. One way to counteract this threat to society is to identify novel ways to rapidly screen and identify drug candidates in living cells. Developing fluorescent antibiotics that can enter microorganisms and be displaced by potential antimicrobial compounds is an important but challenging endeavor due to the difficulty in entering bacterial cells. We developed a cell-based assay using a fluorescent aminoglycoside molecule that allows for the rapid and direct characterization of aminoglycoside binding in a population of bacterial cells. The assay involves the accumulation and competitive displacement of a fluorescent aminoglycoside binding probe in Escherichia coli as a Gram-negative bacterial model. The assay was optimized for high signal-to-background ratios, ease of performance for reliable outcomes, and amenability to high-throughput screening. We demonstrate that the fluorescent binding probe shows a decrease in fluorescence with cellular uptake, consistent with RNA binding, and also shows a subsequent increase upon the addition of the positive control neomycin. Fluorescence intensity increase with aminoglycosides was indicative of their relative binding affinities for A-site rRNA, with neomycin having the highest affinity, followed by paromomycin, tobramycin, sisomicin, and netilmicin. Intermediate fluorescence was found with plazomicin, neamine, apramycin, ribostamicin, gentamicin, and amikacin. Weak fluorescence was observed with kanamycin, hygromycin, streptomycin, and spectinomycin. A high degree of sensitivity was observed with aminoglycosides known to be strong binders for the 16S rRNA A-site compared with antibiotics that target other biosynthetic pathways. The quality of the optimized assay was excellent for planktonic cells, with an average Z' factor value of 0.80. In contrast to planktonic cells, established biofilms yielded an average Z' factor of 0.61. The high sensitivity of this cell-based assay in a physiological context demonstrates significant potential for identifying potent new ribosomal binding antibiotics.

Encapsulation of Rifampicin in Solid Lipid Nanoparticles by Microwave‐Assisted Microemulsion Method

AbstractRifampicin (RF) is a potent antibiotic, but its clinical effectiveness is limited by poor water solubility and stability. To overcome these limitations, RF is encapsulated in solid‐lipid nanoparticles (SLNs) using a one‐pot microwave microemulsion method. This study aimed to synthesize and characterize RF‐loaded SLNs, evaluating their physicochemical characteristics and antimicrobial efficacy. The synthesized SLNs exhibit particle sizes ranging from 150 to 200 nm, with a high encapsulation efficiency of ≈55% and high loading capacity. The particles are imaged by cryogenic‐transmission electron microscopy and found to be circular and elongated, with RF homogenously distributed throughout the particles. The RF‐loaded SLNs demonstrate potent antimicrobial activity, as evidenced by disc diffusion assays. The SLNs exhibits a sustained drug release profile, highlighting their potential as an effective drug delivery system for antimicrobial treatment. These findings suggest that SLNs can enhance the stability, bioavailability, and therapeutic efficacy of hydrophobic drugs like RF.

Synthetic studies on the tetrasubstituted D-ring of cystobactamids lead to potent terephthalic acid antibiotics

Novel scaffolds for broad-spectrum antibiotics are rare and in strong demand because of the increase in antimicrobial resistance. The cystobactamids, discovered from myxobacterial sources, have a unique hexapeptidic scaffold with five arylamides and possess potent, resistance-breaking properties. This study investigates the role of the central D-ring pharmacophore in cystobactamids, a para-aminobenzoic acid (PABA) moiety that is additionally substituted by hydroxy and isopropoxy functions. We varied the two oxygenated substituents and replaced both amide connectors with bioisosteres. Synthetic routes were developed that included metal-mediated aromatic functionalization or heterocycle formations, leading to 19 novel analogues. The antibiotic efficacy of all analogues was determined against bacteria from the ESKAPE pathogen panel. While the replacement and the repositioning of hydroxy and isopropoxy substituents was not advantageous, exchanging PABA by terephthalic acid amides led to the highly potent analogue 42 with broad-spectrum activity, insensitivity towards AlbD-mediated degradation and promising pharmacokinetic properties in mice. The study highlights the steep structure-activity relationships in the tetrasubstituted D-ring and a surprisingly favorable reversion of the amide connecting C and D.

Diagnosis and Treatment of Giardia lamblia Article Review

Giardia lamblia is a microscopic parasite belonging to the genus Giardia, renowned for its complex antigenic mech- anisms. This parasite predominantly inhabits the small intestine, leading to a range of symptoms, including diarrhea, abdominal pain, and discomfort, affecting both humans and various animals such as dogs, cats, cattle, and sheep. The transmission of Giardia lamblia occurs through contaminated food, surface water, and fecal matter. The parasite spreads primarily through the fecal-oral route when hands contaminated with infected feces is exposed to the mouth, or when the infected cysts are ingested directly or indirectly. Giardia lamblia goes through two primary life stages after entering the host: the vegetative trophozoite phase and the cyst phase. The parasite takes 9 to 15 days to begin incubating before symptoms appear. Giardiasis is usually diagnosed by stool analysis, employing direct smear techniques with wet or saline preparations. A duodenal biopsy may be necessary in certain rare cases after a positive serological test since duodenal aspiration has been shown to identify up to 80% more cases than stool analysis, making it essential for successful treatment and prevention plans. Numerous diagnostic techniques are available to determine whether Giardia lamblia is present. To find cysts or trophozoites in stool samples, concentration techniques and direct fiXation methods are used. Cysts are typically visible on wet preparation slides, although the trophozoite stage is more likely to be visible on permanent mounts. Furthermore, the parasites and their antigens are found using sophisticated diagnostic methods such enzyme immunoassay and immunofluorescence, respectively. There are various potent antibiotics used in the treatment of giardiasis. Known by its brand name Flagyl, metronidazole is the most generally prescribed antibiotic. On the other hand, adverse reactions like nausea and a metallic aftertaste are reported. Tinidazole, another potent antibiotic that is taken in a single dose, with adverse effects that are comparable to those of metronidazole. In order to avoid negative responses, patients receiving therapy with metronidazole or tinidazole must abstain from alcohol. The pathogen Giardia lamblia is the source of giardiasis and poses a significant hazard to human and animal health. The spread of giardiasis and its effects can be considerably decreased by being aware of the parasite’s life cycle, employing suitable diagnostic techniques, and adhering to recommended treatment regimens.

Saga of Soggy Sauerkraut

The creation of undesirable (soggy) sauerkraut resulted in the loss of $1,000,000 worth of organic sauerkraut in 2022, which prompted a multistep investigation of the cause and potential solution. The cause of this condition has been previously reported as unique fermentation conditions and the lack of key trace nutrients essential for cabbage (Brassica oleracea var. capitata) cell wall integrity. Because the condition was limited to organic sauerkraut in 2022, this investigation initially focused on differences in fermentation conditions between organic and conventional sauerkraut. No differences in fermentation conditions accounted for the condition; therefore, attention was focused on analyzing the mineral content of cabbage grown for sauerkraut production that pinpointed a deficiency in critical micronutrients such as iron, copper, manganese, boron, and zinc. This deficiency was traced to the use of poultry manure that was contaminated with glyphosate residue from conventionally fed turkeys and chickens that consumed genetically engineered (GE) feed and used as the fertilizer for organic cabbage production. The presence of glyphosate, a potent mineral chelator and antibiotic, was identified as a significant factor that impairs the absorption and physiological function of essential minerals in the shikimate metabolic pathway whereby cell walls and lignin are produced, thus compromising the structural quality of the sauerkraut. After this discovery, the study progressed to evaluate various remediation strategies aimed at eliminating glyphosate from the soil and restoring nutrient uptake. Corn grain and silage were selected as the test crops for this phase. Among the tested remediation solutions were raw sauerkraut juice containing Lactobacillus plantarum, which is reported to degrade glyphosate in the rumen of dairy cows and two patented proprietary microbial mixtures, PB027 and PB027SK, that degrade glyphosate by all three of the known metabolic pathways. These treatments were specifically formulated to degrade residual glyphosate in the soil. The results showed that these interventions could reduce soil glyphosate levels by 80% to 90% within 6 to 7 months to significantly enhance both the yield and quality of corn grain and silage. The increase in corn grain yield from glyphosate degradation on the Shiocton silt loam soil was 907.89 kg·ha−1 (13.5 bushels/acre). The increase in yield on the irrigated Kidder sandy loam soil was quantified at 726.31 kg·ha−1 (10.8 bushels/acre) for corn grain and 6.62 t·ha−1 (2.68 t/acre) for silage, with an additional improvement in silage feed quality beneficial for milk production. The findings underscore the importance of addressing both micronutrient sufficiency and glyphosate residue in soil to ensure the optimal growth of cabbage and the quality of sauerkraut produced. By successfully identifying manure as a subtle source of nutrient immobilization and implementing effective soil remediation techniques, this research highlights a clear path forward for improving crop yield and quality to ultimately enhance the structural integrity and consumer acceptance of sauerkraut. This study has broader applications for the nutritional content and crop yields of many organic crops that use conventional poultry and animal manures that may contain glyphosate in desiccated plant tissues or GE feeding operations.

Solid-state properties and antibiotic potency of levofloxacin – dicarboxylate salts prepared by the green method

This research dealt with the green methods to react levofloxacin (LF) with dicarboxylate acids: oxalic acid (OX), succinic acid (SA), malonic acid (MN), and maleic acid (MA) and investigated its impact on the LF’s stability, solubility, and antimicrobial potency, which never been reported before. Solvent-dropped grinding (SDG) using ethanol 95 % was used to prepare the organic antibiotic salts, reducing the solvent usage significantly compared to the conventional solvent evaporation method, supported with solid-state characterization using electrothermal, differential scanning calorimetry and powder X-ray diffractometry. Next, Fourier Transform Infrared Spectroscopy and Nuclear Magnetic Resonance (1H-NMR) confirmed and determined the interaction structure between LF and the acids. Afterward, the benefits of the LF-dicarboxylate salts were investigated, including stability, solubility, and antibiotic potency. The results demonstrated that the SDG could produce LF-OX hydrate, LF-SA hydrate, and anhydrous LF-MN in a (1:1) molar ratio, with a diffractogram never yet explained. Meanwhile, the LF-MA (1:1) salt solid-state structure was identical to the reported one. Notably, these LF-dicarboxylates showed better solubility, stability, and potency than LF alone, suggesting potential for further dosage formulations.

Antimicrobial Potency of Nor-Pyochelin Analogues and Their Cation Complexes against Multidrug-Resistant Pathogens.

The opportunistic pathogen Pseudomonas aeruginosa develops increasing resistance toward even the most potent antibiotics. Like other bacteria, the pathogen produces a number of virulence factors including metallophores, which constitute an important group. Pseudomonads produce the iron-chelating metallophore (siderophore) pyochelin, which, in addition to its iron-scavenging ability, is an effector for the transcriptional regulator PchR in its FeIII-bound form (ferripyochelin). In the present study, docking studies predicted a major ferripyochelin binding site in PchR, which prompted the exploration of nor-pyochelin analogues to produce tight binding to PchR, and thereby upregulation of the pyochelin metabolism. In addition, we investigated the effects of using the analogues to bind the antimicrobial cations GaIII and InIII. Selected analogues of nor-pyochelin were synthesized, and their GaIII- and InIII-based complexes were assessed for antimicrobial activity. The results indicate that the GaIII complexes inhibit the pathogens under iron-limited conditions, while the InIII-based systems are more effective in iron-rich media. Several of the GaIII complexes were shown to be highly effective against a multidrug-resistant P. aeruginosa clinical isolate, with minimum inhibitory concentrations (MICs) of ≤1 μg/mL. Similarly, two of the InIII-based systems were particularly effective against the isolate, with an MIC of 8 μg/mL. These results show high promise in comparison with other, traditionally potent antibiotics, as the compounds generally indicated low cytotoxicity toward mammalian cells. Preliminary mechanistic investigations using pseudomonal transposon mutants suggested that the inhibitory effects of the InIII-based systems could be due to acute iron deficiency as a result of InIII-bound bacterioferritin.

Pattern-based genome mining guides discovery of the antibiotic indanopyrrole A from a marine streptomycetef.

Terrestrial actinomycetes in the genus Streptomyces have long been recognized as prolific producers of small molecule natural products, including many clinically important antibiotics and cytotoxic agents. Although Streptomyces can also be isolated from marine environments, their potential for natural product biosynthesis remains underexplored. The MAR4 clade of largely marine-derived Streptomyces has been a rich source of novel halogenated natural products of diverse structural classes. To further explore the biosynthetic potential of this group, we applied pattern-based genome mining leading to the discovery of the first halogenated pyrroloketoindane natural products, indanopyrrole A (1) and B (2), and the bioinformatic linkage of these compounds to an orphan biosynthetic gene cluster (BCG) in 20 MAR4 genomes. Indanopyrrole A displays potent broad-spectrum antibiotic activity against clinically relevant pathogens. A comparison of the putative indanopyrrole BGC with that of the related compound indanomycin provides new insights into the terminal cyclization and offloading mechanisms in pyrroloketoindane biosynthesis. Broader searches of public databases reveal the rarity of this BGC while also highlighting opportunities for discovering additional compounds in this uncommon class.

The Synergy between Antibiotics and the Nanoparticle-Based Photodynamic Effect.

Antimicrobial resistance (AMR) is a growing global health concern, necessitating innovative strategies beyond the development of new antibiotics. Here, we employed NdYVO4:Eu3+ nanoparticles, which can persistently produce reactive oxygen species (ROS) after stopping the light, as a model of photodynamic nanoparticles and demonstrated that the photodynamic effect can serve as an adjuvant with antibiotics to effectively reduce their minimum inhibitory concentration. These preirradiated nanoparticles could penetrate the bacterial cell membrane, significantly enhancing the potency of antibiotics. We showed that the synergy effect could be attributed to disrupting crucial cellular processes by ROS, including damaging cell membrane proteins, interfering with energy supply, and inhibiting antibiotic metabolism. Our findings suggested that complementing the photodynamic effect might be a robust strategy to enhance antibiotic potency, providing an alternative antibacterial treatment paradigm.

Antibacterial and mechanism of action studies of boxazomycin A.

Boxazomycins A-C are potent broad-spectrum antibiotics isolated from Actinomycetes strain G495-1 in 1987. We now report that boxazomycin A inhibits bacterial growth by selectively inhibiting protein synthesis, its effect is bacteriostatic, and it is equally active against drug resistant bacterial strains. No cross-resistance to protein synthesis inhibitors was observed suggesting that its inhibition is distinct from clinical protein synthesis inhibitors. We also report in vivo efficacy in a Staphylococcus aureus murine infection model supported by corresponding pharmacokinetic studies.

Establishing the Comprehensive Structure−Activity Relationship of the Natural Antibiotic Kibdelomycin/Amycolamicin

Abstract: Kibdelomycin (KBD) and amycolamicin (AMM) are potent natural antibiotics effective against antibiotic‐resistant Gram‐positive pathogens, including vancomycin‐intermediate Staphylococcus aureus (S. aureus, VISA), methicillin‐resistant S. aureus (MRSA), and quinolone‐resistant S. aureus (QRSA). Their antibacterial activity stems from an unprecedented dual mechanism: the lower binding sites occupy the adenosine triphosphate (ATP) binding pocket of bacterial type II topoisomerases, while the upper binding sites disrupt the enzyme dimer interface. This dual action, combined with their unique chemical structures, positions KBD and AMM as promising scaffolds for developing new antibiotics. However, the structure‐activity relationship (SAR) of KBD/AMM remains underexplored due to their highly complex chemical structures. In this study, we utilized total synthesis to produce KBD/AMM analogs with various site modifications and evaluated their antimicrobial activities. Our findings establish the first comprehensive SAR for KBD/AMM, paving the way for the development of novel KBD/AMM‐based antibiotics.

Establishing the Comprehensive Structure-Activity Relationship of the Natural Antibiotic Kibdelomycin/Amycolamicin.

Kibdelomycin (KBD) and amycolamicin (AMM) are potent natural antibiotics effective against antibiotic-resistant Gram-positive pathogens, including vancomycin-intermediate Staphylococcus aureus (S. aureus, VISA), methicillin-resistant S. aureus (MRSA), and quinolone-resistant S. aureus (QRSA). Their antibacterial activity stems from an unprecedented dual mechanism: the lower binding sites occupy the adenosine triphosphate (ATP) binding pocket of bacterial type II topoisomerases, while the upper binding sites disrupt the enzyme dimer interface. This dual action, combined with their unique chemical structures, positions KBD and AMM as promising scaffolds for developing new antibiotics. However, the structure-activity relationship (SAR) of KBD/AMM remains underexplored due to their highly complex chemical structures. In this study, we utilized total synthesis to produce KBD/AMM analogs with various site modifications and evaluated their antimicrobial activities. Our findings establish the first comprehensive SAR for KBD/AMM, paving the way for the development of novel KBD/AMM-based antibiotics.

Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA assisted uptake and ribosomal protein RplL sensitivity.

Gonorrhea, which is caused by Neisseria gonorrhoeae , is the second most reported sexually transmitted infection worldwide. The increasing appearance of isolates that are resistant to approved therapeutics raises the concern that gonorrhea may become untreatable. Here, we serendipitously identified oxydifficidin as a potent N. gonorrhoeae antibiotic through the observation of a Bacillus amyloliquefaciens contaminant in a lawn of N. gonorrhoeae . Oxydifficidin is active against both wild- type and multidrug-resistant N. gonorrhoeae . It's potent activity results from a combination of DedA- assisted uptake into the cytoplasm and the presence of an oxydifficidin-sensitive ribosomal protein L7/L12 (RplL). Our data indicates that oxydifficidin binds to the ribosome at a site that is distinct from other antibiotics and that L7/L12 is uniquely associated with its mode of action. This study opens a potential new avenue for addressing antibiotic resistant gonorrhea and underscores the possibility of identifying overlooked natural products from cultured bacteria, particularly those with activity against previously understudied pathogens.

Single Atom Engineered Antibiotics Overcome Bacterial Resistance.

The outbreak of antibiotic-resistant bacteria, or "superbugs", poses a global public health hazard due to their resilience against the most effective last-line antibiotics. Identifying potent antibacterial agents capable of evading bacterial resistance mechanisms represents the ultimate defense strategy. This study shows that -the otherwise essential micronutrient- manganese turns into a broad-spectrum potent antibiotic when coordinated with a carboxylated nitrogen-doped graphene. This antibiotic material (termed NGA-Mn) not only inhibits the growth of a wide spectrum of multidrug-resistant bacteria but also heals wounds infected by bacteria in vivo and, most importantly, effectively evades bacterial resistance development. NGA-Mn exhibits up to 25-fold higher cytocompatibility to human cells than its minimum bacterial inhibitory concentration, demonstrating its potential as a next-generation antibacterial agent. Experimental findings suggest that NGA-Mn acts on the outer side of the bacterial cell membrane via a multimolecular collective binding, blocking vital functions in both Gram-positive and Gram-negative bacteria. The results underscore the potential of single-atom engineering toward potent antibiotics, offering simultaneously a long-sought solution for evading drug resistance development while being cytocompatible to human cells.