Promising Antibiotic Research Articles

Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies.

The rise of antibiotic resistance, coupled with a dwindling antibiotic pipeline, presents a significant threat to public health. Consequently, there is an urgent need for novel therapeutics targeting antibiotic-resistant pathogens. Nisin, a promising peptide antibiotic, exhibits potent bactericidal activity through a mechanism distinct from that of clinically used antibiotics. However, its cationic nature leads to hemolysis and cytotoxicity, which has limited its clinical application. Here, nanodelivery systems have been developed by mimicking the mechanisms bacteriophages use to deliver their genomes to host bacteria. These systems utilize bacteriophage receptor-binding proteins conjugated to loading modules, enabling efficient targeting of bacterial pathogens. Peptide antibiotics are loaded via dynamic covalent bonds, allowing for infection microenvironment-responsive payload release. These nanodelivery systems demonstrate remarkable specificity against target pathogens and effectively localize to bacteria-infected lungs in vivo. Notably, they significantly reduce the acute toxicity of nisin, rendering it suitable for intravenous administration. Additionally, these bacteriophage-mimicking nanomedicines exhibit excellent therapeutic efficacy in a mouse model of MRSA-induced pneumonia. The facile synthesis, potent antimicrobial performance, and favorable biocompatibility of these nanomedicines highlight their potential as alternative therapeutics for combating antibiotic-resistant pathogens. This study underscores the effectiveness of bacteriophage mimicry as a strategy for transforming peptide antibiotics into viable therapeutics.

Total Synthesis and Structural Reassignment of the Antitubercular Natural Product Evybactin.

The escalating threat posed by antibiotic resistance is a global concern and underscores the need for new antibiotics. In this context, the recent discovery of evybactin, a nonribosomal depsipeptide antibiotic that selectively and potently inhibits the growth of M. tuberculosis, is particularly noteworthy. Here, we present the first total synthesis of this natural product, along with a revision of its assigned structure. Our studies revealed a disparity between the structure originally proposed for evybactin and its actual configuration. Specifically, the 3-methylhistidine residue present in the evybactin core macrocycle was found to be of the d-configuration rather than the previously assigned l-His(Me). Having addressed this, we further optimized our solid-phase synthetic route to provide access to evybactin on a multi-hundred-milligram scale. Access to such quantities will allow for more comprehensive studies with this promising antibiotic.

Divergent Tandem Acyl Carrier Proteins Necessitate In-Series Polyketide Processing in the Leinamycin Family.

The leinamycin family of polyketides are promising antitumor antibiotics, yet several aspects of their biosynthesis remain elusive. All leinamycin family members bear a sulfur-containing moiety which is essential for the anticancer activity exhibited by leinamycin. The key building blocks required for the incorporation of these functionalities are introduced in the final module of the polyketide synthase (PKS), which elegantly combines β-branching and thiocysteine incorporation to generate a diverse library of sulfur-based molecular scaffolds. Two acyl carrier proteins (ACPs) form a key didomain component of this module, but their amino acid sequence divergence has brought into question the common notion of functional equivalence. Here, we provide unprecedented functional evidence that these tandem ACPs play distinct roles in the final module of polyketide assembly. Using the weishanmycin biosynthetic pathway as a template, the in vitro reconstitution of key polyketide chain extension and β-branching steps in this module has revealed strict functional selectivity for a single ACP. Furthermore, we propose a cryptic transacylation step must occur prior to polyketide off-loading and cyclization. Altogether, these mechanistic investigations suggest that an atypical in-series mechanism underpins sulfur incorporation in the leinamycin family, and provides significant progress towards delineating their late-stage assembly.

Divergent Tandem Acyl Carrier Proteins Necessitate In‐Series Polyketide Processing in the Leinamycin Family

AbstractThe leinamycin family of polyketides are promising antitumor antibiotics, yet several aspects of their biosynthesis remain elusive. All leinamycin family members bear a sulfur‐containing moiety which is essential for the anticancer activity exhibited by leinamycin. The key building blocks required for the incorporation of these functionalities are introduced in the final module of the polyketide synthase (PKS), which elegantly combines β‐branching and thiocysteine incorporation to generate a diverse library of sulfur‐based molecular scaffolds. Two acyl carrier proteins (ACPs) form a key didomain component of this module, but their amino acid sequence divergence has brought into question the common notion of functional equivalence. Here, we provide unprecedented functional evidence that these tandem ACPs play distinct roles in the final module of polyketide assembly. Using the weishanmycin biosynthetic pathway as a template, the in vitro reconstitution of key polyketide chain extension and β‐branching steps in this module has revealed strict functional selectivity for a single ACP. Furthermore, we propose a cryptic transacylation step must occur prior to polyketide off‐loading and cyclization. Altogether, these mechanistic investigations suggest that an atypical in‐series mechanism underpins sulfur incorporation in the leinamycin family, and provides significant progress towards delineating their late‐stage assembly.

A novel methionyl-tRNA synthetase inhibitor targeting gram-positive bacterial pathogens.

New antibiotics are needed to treat gram-positive bacterial pathogens. MRS-2541 is a novel inhibitor of methionyl-tRNA synthetase with selective activity against gram-positive bacteria. The minimum inhibitory concentrations (MICs) against Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus species range from 0.063 to 0.5 µg/mL. Given orally to mice at 50 mg/kg every 8 hours, MRS-2541 shows sustained plasma levels well above these MICs. In the mouse thigh infection model, MRS-2541 decreased methicillin-resistant Staphylococcus aureus and Streptococcus pyogenes bacterial loads to the same degree as linezolid. MRS-2541 is a promising new antibiotic for development against skin and soft tissue infections.

Translational research priorities for bacteriophage therapeutics.

The growing threat of antimicrobial resistant (AMR) bacterial pathogens coupled with the relative dearth of promising novel antibiotics requires the discovery and development additional medical interventions. Over the past decade bacteriophages have emerged one of the most promising new tools to combat AMR pathogens. Anecdotal clinical experiences under so-called 'compassionate use' regulatory pathways as well as a limited number of clinical trials have provided ample evidence of safety and early evidence of efficacy. For phages to reach their full potential it is critical that rigorous clinical trials be conducted that define their optimal use and that enable regulatory authorities to support the commercialization required to afford global access. The clinical development of phage therapeutics requires the design and execution of clinical trials that take full advantage of lessons learned from a century of antibiotic development and that use clinical investigation as a platform in which aspects of phage biology that are critical to therapeutics are more clearly elucidated. Translational research that elucidates phage biology in the context of clinical trials will promote highly relevant hypothesis-driven work in basic science laboratories and will greatly accelerate the development of the field of phage therapeutics.

The Diverse Activities and Mechanisms of the Acylphloroglucinol Antibiotic Rhodomyrtone: Antibacterial Activity and Beyond.

Background/Objectives: The rose myrtle Rhodomyrtus tomentosa is a medicinal plant used in traditional Asian medicine. The active compound in R. tomentosa leaf extracts is rhodomyrtone, a chiral acylphloroglucinol. Rhodomyrtone exhibits an impressive breadth of activities, including antibacterial, antiviral, antiplasmodial, immunomodulatory, and anticancer properties. Its antibacterial properties have been extensively studied. Methods: We performed a comprehensive literature review on rhodomyrtone and summarized the current knowledge about this promising acylphloroglucinol antibiotic and its diverse functions in this review. Results: Rhodomyrtone shows nano to micromolar activities against a broad range of Gram-positive pathogens, including multidrug-resistant clinical isolates, and possesses a unique mechanism of action. It increases membrane fluidity and creates hyperfluid domains that attract membrane proteins prior to forming large membrane vesicles, effectively acting as a membrane protein trap. This mechanism affects a multitude of cellular processes, including cell division and cell wall synthesis. Additionally, rhodomyrtone reduces the expression of inflammatory cytokines, such as TNF-α, IL-17A, IL1β, and IL8. Generally showing low toxicity against mammalian cells, rhodomyrtone does inhibit the proliferation of cancer cell lines, such as epidermal carcinoma cells. The primary mechanism behind this activity appears to be the downregulation of adhesion kinases and growth factors. Furthermore, rhodomyrtone has shown antioxidant activity and displays cognitive effects, such as decreasing depressive symptoms in mice. Conclusions: Rhodomyrtone shows great promise as therapeutic agent, mostly for antibacterial but also for diverse other applications. Yet, bottlenecks such as resistance development and a better understanding of mammalian cell toxictiy demand careful assessment.

Tubulin Homologs in Bacteria and Archaea

While cytoskeletal proteins have long been considered to be present only in eukaryotes, but not in prokaryotes, homologs of the major cytoskeletal proteins, including tubulin, have been discovered in bacteria and archaea in the last 30 years. The properties of tubulin homologs, as well as of the cytoskeleton-like structures they form in prokaryotic cells, vary and differ significantly from the relevant properties of eukaryotic tubulins. The comparison of prokaryotic tubulin homologs with each other seems therefore to be an interesting task and thus is the goal of the current review. We consider such tubulin homologs found in bacteria and archaea as FtsZ, TubZ, PhuZ, BtubA/BtubB, CetZ, etc. The ability of various tubulin homologs to act as targets for pharmaceuticals, similar to the FtsZ protein, which is already a target for promising antibiotics, is also discussed.

Genetic and in-silico approaches for investigating the mechanisms of ciprofloxacin resistance in Salmonella typhi: Mutations, extrusion, and antimicrobial resistance

Salmonella enterica serovar Typhi spreads typhoid infection in humans through the consumption of contaminated food and water. Poor sanitation plays a pivotal role in its dissemination. Over time, the bacterium has acquired resistance to many promising antibiotics, posing a growing global health concern and hindering the achievement of sustainable development goals. This study aims to elucidate the molecular complexity of fluoroquinolone resistance, a first-line treatment for typhoid infection. To achieve this aim, 80 clinical isolates were collected from various diagnostic laboratories. These isolates were confirmed based on morphological characteristics and biochemical tests. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates were identified using the Kirby-Bauer disc diffusion method. The mechanism of ciprofloxacin resistance was investigated by sequencing the quinolone resistance-determining region (QRDR) genes and identifying the presence of the qnrS1 gene. As a result of this study, 60 % of isolates showed resistance to ciprofloxacin. At the same time, the qnrS1 gene was present in all the selected strains while mutation analysis identified significant mutation in QRDR of DNA gyrase subunit A (gyrA) and Topoisomerase IV (parC) gene. The combinatorial effect was further investigated by downloading 286 draft genomes. The Mutation analysis reveals significant mutations at gyrA S83F, gyrA D87N, gyrA S83Y, gyrB S464F, parC S80I, and parE L416F. Additionally, docking analysis indicates reduced binding affinity and altered solvent accessibility, which show the structural changes at mutation sites. This study provides crucial insights that mutation reduces the binding affinity while qnrS1 acts as a transport channel to extrude the ciprofloxacin. In the future, further validation through experimental mutagenesis is recommended, for targeted therapeutic interventions against the mounting threat of antibiotic-resistant S. Typhi.

In Vivo Effect of Halicin on Methicillin-Resistant Staphylococcus aureus-Infected Caenorhabditis elegans and Its Clinical Potential.

Recently, the high proportion of methicillin-resistant Staphylococcus aureus infections worldwide has highlighted the urgent need for novel antibiotics to combat this crisis. The recent progress in computational techniques for use in health and medicine, especially artificial intelligence (AI), has created new and potential approaches to combat antibiotic-resistant bacteria, such as repurposing existing drugs, optimizing current agents, and designing novel compounds. Halicin was previously used as a diabetic medication, acting as a c-Jun N-terminal protein kinase (JNK) inhibitor, and has recently demonstrated unexpected antibacterial activity. Although previous efforts have highlighted halicin's potential as a promising antibiotic, evidence regarding its effectiveness against clinical strains remains limited, with insufficient proof of its clinical applicability. In this study, we sought to investigate the antibacterial activity of halicin against MRSA clinical strains to validate its clinical applicability, and a C. elegans model infected by MRSA was employed to evaluate the in vivo effect of halicin against MRSA. Our findings revealed the antibacterial activity of halicin against methicillin-resistant S. aureus clinical strains with MICs ranging from 2 to 4 µg/mL. Our study is also the first work to evaluate the in vivo effect of halicin against S. aureus using a C. elegans model, supporting its further development as an antibiotic.

Enhancing the therapeutic window for Spectinamide anti-tuberculosis Agents: Synthesis, Evaluation, and activation of phosphate prodrug 3408

Spectinamides are a novel class of narrow-spectrum antitubercular agents with the potential to treat drug-resistant tuberculosis infections. Spectinamide 1810 has shown a good safety record following subcutaneous injection in mice or infusion in rats but exhibits transient acute toxicity following bolus administration in either species. To improve the therapeutic index of 1810, an injectable prodrug strategy was explored. The injectable phosphate prodrug 3408 has a superior maximum tolerated dose compared to 1810 or Gentamicin. Following intravenous administration in rodents, prodrug 3408 was quickly converted to 1810. The resulting 1810 exposure and pharmacokinetic profile after 3408 administration was identical to equivalent molar amounts of 1810 given directly by intravenous administration. 3408 and the parent 1810 exhibited similar overall efficacy in a BALB/c acute tuberculosis efficacy model. Delivery of 1810 in phosphate prodrug form, therefore, holds the potential to improve further the therapeutic index of an already promising tuberculosis antibiotic.

Organotin (IV) complexes: Synthesis, characterization, DFT, and molecular docking studies unveiling their potential biomedical uses

This study investigates organotin (IV) complexes derived from the recently synthesized quinazoline Schiff base ligand (L). The research involves synthesizing and characterizing these complexes, including elemental analysis, UV–visible, FT‐IR, mass spectra, and conductometric measurements. Advanced studies such as density functional theory (DFT) are employed to gain insights into the stable electronic configuration. Specifically, the study explores the proposed geometry, revealing a distorted octahedral structure for the complexes. The findings contribute as critical molecular characteristics of these newly synthesized complexes, paving the way for potential applications in diverse fields, including medicinal chemistry. Through an investigation into the antimicrobial properties, the efficacy of the synthesized compounds was assessed against a diverse range of bacterial and fungal strains. Remarkably, the complexes demonstrated significant antimicrobial activities, showing potential applications in combating various microbial infections. In an extended exploration of their medical utility, the compounds were examined for their antibiotic properties against Helicobacter pylori. The Schiff base and its metal complexes emerged as promising antibiotics with notable efficacy against H. pylori, suggesting their potential in addressing infections associated with this bacterium. Furthermore, the antitumor potential of the synthesized complexes was investigated, focusing on their impact on MCF‐7 (Breast carcinoma) cells. The organotin (IV) Schiff base complexes in this research showed remarkable efficacy, evidenced by their notably low IC50 values (9, 10, 11 μg/mL) in comparison with cisplatin. In addition to their potent antitumor effects, these complexes exhibited reduced cytotoxicity toward normal cells (VERO cells) compared with cisplatin. The investigation extends to molecular docking, where this approach aims to elucidate their interactions with specific protein structures, including (2JFZ, 1SC7, and 6W41). The primary objective is to clarify the potential properties of these compounds, focusing on their antibiotic efficacy, anti‐H. pylori activity, antitumor potential, and anti‐COVID‐19 properties.

Zn(II) enhances the antimicrobial effect of chloroxine and structural analogues against drug-resistant ESKAPE pathogens in vitro

The emerging antibiotic-resistant bacteria, especially the “ESKAPE” pathogens, pose a continuous threat to global health. In this study, we explored metalloantibiotics as promising therapeutics and innovative antimicrobial agents. The role of metal in the antimicrobial activity of chloroxine (5,7-dichloro-8-hydroxyquinoline), as a metalloantibiotic, was investigated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and UV–visible spectroscopy and PAR (4-(2-pyridylazo)-resorcinol) competition assays. Both chloroxine and its structural analogues exhibited increased antibacterial potency against Gram-positive bacteria compared to Gram-negative bacteria. The introduction of exogenous manganese or zinc ions significantly boosted chloroxine’s antibacterial efficacy against Gram-negative bacteria, including the notorious ESKAPE pathogens. However, the enhanced antibacterial activity induced by zinc ions could be negated in the presence of copper or ferrous iron ions, as well as changes in oxygen availability, highlighting the involvement of proton motive force, oxidative and antioxidative systems. Notably, chloroxine effectively inhibited the enzymatic activity of superoxide dismutase (SOD). In addition, chloroxine could reverse polymyxin and carbapenem resistance in E. coli in vitro. Therefore, these results suggested that chloroxine with zinc ions are promising therapeutics and antibiotics potentiator to combat multidrug-resistant ESKAPE pathogens.

Identification of clusters of secondary metabolite biosynthetic genes in the Camelina sativa genome

Multidrug-resistant pathogens pose an earnest risk to human health. Therefore, new antibiotics need to be developed quickly. Most of the antibiotics we use today are derived from secondary metabolites, which are produced by plants. Genome mining tools allow us to detect biosynthetic gene clusters (BGCs) responsible for the production of secondary metabolites. Focusing on the most promising BGCs-coding antibiotics with unique pathways is currently a challenge. In silico approach like genome mining are used to visualise the action of these bioactive chemicals. Camelina sativa is a well-known medicinal plant and it would be interesting to study its secondary metabolites. In this work, we found seven bioactive compounds in this plant using the genome mining approach. Further, the clusters of genes involved in the biosynthesis of these compounds were analysed with their metabolic pathways. This work illuminates new ground on the evolution of BGCs for the nutritional improvement of C. sativa.

Microwave-assisted click synthesis, characterisation, and In silico studies of novel 2H-chromene-1,2,3-triazolyl glycoconjugates as potent anticancer and antibacterial agents

A series of novel 2H-chromene-1,2,3-triazolyl glycoconjugates 10a-w were synthesized, well characterized and evaluated for their in vitro antimicrobial and anticancer activities. Among the tested compounds, 10a, 10b, 10u, 10v, and 10w exhibited the most excellent potency against both gram-positive (S. aureus) and gram-negative (E. coli) bacterial strains relative to the standard drug, Gentamicin. The anticancer results showed that in MCF-7 cell line all the tested compounds exhibited better activity as compared to other two cancer cell lines (MDA-MB-231 and A549). Compounds 10t, 10u, 10v, and 10w showed significant cytotoxicity against MCF-7 cell line. The molecular docking studies suggested that all the four potent compounds exhibited a greater affinity for the selected receptors. Experimentally and computationally observed structure-activity relationships indicates, -OCH3 group at R2 position in benzopyran ring with tosyl-protected sugar containing compound 10b and benzyl-protected sugar containing compound 10t enhanced the antibacterial and anticancer activity respectively. Frontier molecular orbital analysis of compounds using the global reactivity parameters indicated that benzyl-protected sugar and acetyl-protected sugar containing compounds are stable and exhibits low reactivity. Moreover, molecular electrostatic potential analysis plots clearly showed that the compounds have strong electrophonic reaction potential. Moreover, the assessment of ADMET predictions revealed favourable pharmacokinetic properties of the investigated compounds. Collectively, it was observed that compounds 10u, 10v, and 10w could be considered as promising dual anticancer antibiotic inhibitors.

In vitro and in silico screening and identification of potential bioactive anthraquinones of Morinda lucida benth against pathogenic bacterial target proteins

BackgroundThe use of plant extracts as antibiotics is gaining more attention because bacteria are one of the biggest threats to global health and the resistance of bacteria to antibiotics in humans and animals is increasing. Antibacterial susceptibility is used to determine which specific antibiotics a particular bacterium is sensitive to. This research is focused on the phytochemical, in vitro antibacterial susceptibility, and in silico analysis of Morinda lucida root extracts against gram-negative Pseudomonas aeruginosa and gram-positive Staphylococcus aureus. The root of M. lucida was extracted separately with ethanol, chloroform, and ethyl acetate.ResultsCrude extracts of M. lucida had active antibacterial activity and were a promising natural antibiotic when compared to gentamicin. The in vitro results showed that the extracts of M. lucida had good susceptibility properties against the two drug-resistant bacteria while the in silico showed that 2-hydroxy-1-methoxy anthraquinone is predicted to have a better susceptibility with S. aureus while alizarin has better susceptibility properties against P. aeruginosa. Finally, the MD simulation studies of Alizarin and 9,10-Anthracenedione 2-hydroxy-1- methoxy- define the stability of protein–ligand complexes within a 50 ns time scale.

β-Cyclodextrin/carbon dots-grafted cellulose nanofibrils hydrogel for enhanced adsorption and fluorescence detection of levofloxacin

In this study, a novel hydrogel, β-cyclodextrin/carbon dots-grafted cellulose nanofibrils hydrogel (βCCH), was fabricated for removal and fluorescence determination of levofloxacin (LEV). A comprehensive analysis was performed to characterize its physicochemical properties. Batch adsorption experiments were conducted, revealing that βCCH reached a maximum adsorption capacity of 1376.9 mg/g, consistent with both Langmuir and pseudo-second-order models, suggesting that the adsorption process of LEV on βCCH was primarily driven by chemical adsorption. The removal efficiency of βCCH was 99.2 % under the fixed conditions (pH: 6, initial concentration: 20 mg/L, contact time: 300 min, temperature: 25 °C). The removal efficiency of βCCH for LEV still achieved 97.3 % after five adsorption-desorption cycles. By using βCCH as a fluorescent probe for LEV, a fast and sensitive method was established with linear ranges of 1–120 mg/L and 0.2–1.0 μg/L and a limit of detection (LOD) as low as 0.09 μg/L. The viability of βCCH was estimated based on the economic analysis of the synthesis process and the removal of LEV, demonstrating that βCCH was more cost-effective than commercial activated carbon. This study provides a novel approach for preparing a promising antibiotic detection and adsorption material with the advantages of stability, and cost-effectiveness.

Emergence of Neisseria gonorrhoeae Clone with Reduced Susceptibility to Sitafloxacin in China: An In Vitro and Genomic Study.

Drug-resistant Neisseria gonorrhoeae poses an urgent threat to public health. Recently, sitafloxacin, a new-generation fluoroquinolone, has shown high in vitro activity against drug-resistant N. gonorrhoeae. However, data on its effectiveness in clinical isolates remains limited. In this study, we collected 507 N. gonorrhoeae isolates from 21 hospitals in Shanghai, China, during 2020 and 2021. Antimicrobial susceptibility testing revealed that sitafloxacin minimum inhibitory concentrations (MICs) exhibited a bimodal distribution, ranging from <0.004 to 2 mg/L. The MIC50 and MIC90 for sitafloxacin were 0.125 mg/L and 0.5 mg/L, respectively, which are 32 and 16 times lower than those for ciprofloxacin (4 mg/L and 8 mg/L, respectively). Sitafloxacin demonstrated high in vitro activity against isolates resistant to either ceftriaxone, azithromycin, or both. Notably, among the isolates with reduced sitafloxacin susceptibility (MIC ≥ MIC90), 83.7% (36/43) were identified as sequence type (ST) 8123. Further phylogenetic analysis showed that ST8123 has evolved into two subclades, designated as subclade-I and subclade-II. A majority of the isolates (80%, 36/45) within subclade-I exhibited reduced susceptibility to sitafloxacin. In contrast, all isolates from subclade-II were found to be susceptible to sitafloxacin. Subsequent genomic investigations revealed that the GyrA-S91F, D95Y, and ParC-S87N mutations, which were exclusively found in ST8123 subclade-I, might be linked to reduced sitafloxacin susceptibility. Our study reveals that sitafloxacin is a promising antibiotic for combating drug-resistant N. gonorrhoeae. However, caution is advised in the clinical application of sitafloxacin for treating N. gonorrhoeae infections due to the emergence of a clone exhibiting reduced susceptibility.

Clinical characteristics and antimicrobial susceptibility profiles of Mycobacterium abscessus and Mycobacterium massiliense pulmonary infection

ObjectivesMycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug-susceptibility statuses of different M. abscessus (MAB) subspecies in the Zhejiang Province. MethodsDNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine in vitro susceptibility of imipenem-relebactam (IMP-REL), omadacycline, and other conventional antibiotics. Patient clinical characteristics were collected and analysed. ResultsIn total, 139 M. abscessus, 39 Mycobacterium massiliense, and 1 Mycobacterium bolletii isolates were collected, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. IMP-REL resulted in a twofold reduction in the minimum inhibitory concentration (MIC) value compared with imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. ConclusionsM.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. IMP-REL and omadacycline are promising antibiotics for MABC infection treatment.

Narrow spectrum nano-antibiotic for selective removal of ARB from contaminated water: New insights into stimuli response based on cellular attachment, lysis, and excretion

Narrow spectrum nano-antibiotics are supposedly the future trouble-shooters to improve the efficacy of conventional antimicrobials for treatment of severe bacterial infections, remove contamination from water and diminish the development of antibiotic resistance. In this study, antimicrobial peptide functionalized boron-carbon-nitride nanosheets ((Ant)pep@BCN NSs) are developed that are a promising wastewater disinfector and antibiotic resistant bactericide agent. These nanosheets are developed for selective removal and effective inactivation of antibiotic resistant bacteria (ARB) from water in presence of two virulent bacteria. The (Ant)pep@BCN NSs provide reactive surface receptors specific to the ARB. They mimic muralytic enzymes to damage the cell membrane of ARB. These NSs demonstrate 3-fold higher antimicrobial efficiency against the targeted ARB compared to pristine BCN even at lower concentrations. To the best of our knowledge, this is the first time that functionalized BCN has been developed to remove ARB selectively from wastewater. Furthermore, the (Ant)pep@BCN selectively reduced the microbiological load and led to morphological changes in Gram negative ARB in a mixed bacterial inoculum. These ARBs excreted outer–inner membrane vesicles (OIMVs) of triangular shape as a stimuli response to (Ant)pep@BCN NSs. These novel antimicrobial peptide-NSs have potential to improve treatment efficacy against ARB infections and water contamination.