Combined effect of brazilin-rich extract and lawsone methyl ether against infection-causing bacteria.

Bacterial contamination and infection widely affect the food, pharmaceutical and biomedical industries. Additionally, these bacteria developed resistance to synthetic antibiotics causing public health danger, globally. Natural plant extracts (NPE) are suitable alternatives to synthetic antibiotics to tackle antimicrobial resistance problems. Furthermore, a blend or combination of different NPEs exerts a wide spectrum of antimicrobial activity. Therefore, the combined effect of brazilin-rich extract (BRE) and lawsome methyl ether (LME) against infection-causing common bacteria were evaluated. BRE had a lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against most of the Gram-negative bacteria (Salmonella typhi, Salmonella typhimurium and Pseudomonas aeruginosa) while LME was active against most of the Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus, and Staphylococcus epidermidis). The combination of BRE and LME at 2:1 and 1:1 concentration significantly reduced the MIC value of each compound as compared to either BRE or LME concentration alone (P < 0.05). Further time-kill kinetics revealed a 3.0-3.5 log reduction in Gram-positive bacteria and a 2.5-3.0 log reduction in Gram-negative bacteria during 120 min of incubation, respectively. Therefore, a combination of BRE and LME was recommended as natural antibacterial to synthetic antibiotics for food and pharmaceutical applications.

Deciphering the pharmacological mechanisms of Shenlingbaizhu formula in antibiotic-associated diarrhea treatment: Network pharmacological analysis and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenlingbaizhu (SLBZ) formula, a classical traditional Chinese medicinal (TCM) formula, has been widely used for treating antibiotic-associated diarrhea (AAD). However, the underlying pharmacological mechanisms have not yet been investigated thoroughly. AIM OF THE STUDY: To explore the remission mechanism of SLBZ in the treatment of AAD, we conducted network pharmacological analysis and experimental validation in vitro and in vivo. MATERIALS AND METHODS: In this study, the main compounds of SLBZ were identified by ultra-high-performance liquid chromatography-mass spectroscopy (UHPLC-MS) and online databases. The targets of the active components and AAD-related targets were predicted by network pharmacology, and the potential targets of SLBZ against AAD were obtained. Then the core targets were recognized after Protein-Protein Interaction (PPI) analysis. Based on these, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses were conducted, and the key pathway was screened. Subsequently, molecular docking was performed using Auto Dock Vina to find the key components that played a crucial role in that pathway. Molecular dynamics simulation was performed by Gromacs software to detect the binding mode. Finally, the results were confirmed by in vitro and in vivo experiments. RESULTS: A total of 66 active ingredients of SLBZ were detected by UHPLC-MS, and 128 active ingredients were screened out by network pharmacological analysis. Additionally, 935 drug targets and 1686 AAD-related targets were obtained. Seventy-eight intersected genes were selected as potential therapeutic targets and 19 genes were excavated as core targets. Enrichment analysis revealed PI3K-AKT signaling pathway was the key pathway in SLBZ against AAD. Topological analysis further revealed that JAK2, MTOR, TLR4, and SYK were the key targets affected by SLBZ on the PI3K-AKT pathway, and 52 components of SLBZ were associated with them. Molecular docking and dynamics simulation revealed strong binding affinities between MTOR and diosgenin. Subsequently, after SLBZ treatment, the expression levels of JAK2, MTOR, TLR4, and SYK were found significantly upregulated in the AAD model rats (p < 0.05). The cell experiment further validated the good binding ability between MTOR and diosgenin. CONCLUSION: We demonstrate that the therapeutic effect of SLBZ on AAD was achieved in part by inhibiting the PI3K-AKT pathway.

Unlocking the power of Libidibia ferrea extracts: antimicrobial, antioxidant, and protective properties for potential use in poultry production.

Plant extracts are increasingly recognized as potential prophylactic agents in poultry production due to their diverse bioactive properties. This study investigated the phytochemical and biological properties of Libidibia ferrea (L. ferrea), a plant species native to the Caatinga region of northeastern Brazil. The aim of this study was to identify secondary metabolites and to demonstrate the antimicrobial, antioxidant and protective effects of the plant extract. Three extracts were produced: EHMV, a hydroalcoholic extract from the maceration of pods, and EEMC and EEMV ethanolic extracts from the maceration of peels and pods, respectively, from L. ferrea. High-performance liquid chromatography (HPLC-MS/MS) and atomic absorption spectroscopy (AAS) were used to characterize the metabolites and metals. The antimicrobial activity against Salmonella Galinarum (SG), Salmonella pullorum (SP), Salmonella Heidelberg (SH) and Avian pathogenic Escherichia coli (APEC) was evaluated alone and in combination with probiotic bacteria (Bacillus velenzensis) using agar diffusion and the bactericidal minimum concentration (CBM). The antioxidant potential of the extracts was evaluated in 5 in vitro assays and 6 assays in 3t3 cells. The toxicity of EHMV was tested, and its ability to combat SP infection was demonstrated using a chicken embryo model. The results showed that EHMV exhibited significant antimicrobial activity. The combination of EHMV with BV had synergistic effects, increased antimicrobial activity and induced bacterial sporulation. Composition analysis revealed the presence of 8 compounds, including tannins and phenolic compounds. In vitro antioxidant tests demonstrated that total antioxidant capacity(TAC) activity was increased, and the extract had strong reducing power and notable metal chelating effects. Analysis of 3T3 cells confirmed the protective effect of EHMV against oxidative stress. Toxicity assessments in chicken embryos confirmed the safety of EHMV and its protective effect against SP-induced mortality. EHMV from L. ferrea is rich in proteins and contains essential metabolites that contribute to its antimicrobial and antioxidant properties. When associated with probiotic bacteria such as B. velezensis, this extract increases the inhibition of SH, SG, SP, and APE. The nontoxic nature of EHMV and its protective effects on chicken embryos make it a potential supplement for poultry.

Initial diet shapes resistance-gene composition and fecal microbiome dynamics in young ruminants during nursing.

This study was conducted to examine how colostrum pasteurization affects resistance genes and microbial communities in calf feces. Forty female Holstein calves were randomly assigned to either the control (CON) group, which received unheated colostrum, or the pasteurized colostrum (PAT) group. The calves body weight was measured weekly before morning feeding. Calf starter intake were measured and recorded daily before morning feeding. Samples of colostrum were collected before feeding. Blood was collected on d 1 and 70 before morning feeding. Ten calves were randomly selected from each group (n = 20 calves total) for fecal sampling on d 3, 28, 56 and 70 for subsequent DNA extraction and metagenomic sequencing. Total bacterial counts in the colostrum were markedly higher in the CON group than in the PAT group. Pasteurized colostrum administration substantially reduced the ARO diversity and diminishes the abundance of Enterobacteriaceae, thereby decreasing their contribution to resistance genes. Pasteurization also reduced glucoside hydrolase-66 activity in 3-day-old calves which led to an increase in the activity of aminoglycoside antibiotics, resulting in 52.63 % of PAT-enriched bacteria acquiring aminoglycoside resistance genes. However, from the perspective of overall microbial community, the proportion of aminoglycoside, beta-lactam and tetracycline resistance genes carried by microbial community in PAT group was lower than CON group (P < 0.05). Fecal samples from the PAT group contained greater abundances of Subdoligranulum (P < 0.05) and Lachnospiraceae_NK4A136_group (P < 0.05) on days 28 and 70 compared to CON. Network analysis and abundance variations of the different bacteria obtained by linear discriminant analysis effect size analysis showed that pasteurized colostrum feeding reduced the interactions among related bacteria and maintained stability of the hind-gut microbiome. In conclusion, these findings underscore the intricate interactions between early diet, calf resistance-gene transmission and microbial dynamics, which should be carefully considered in calf-rearing practices.

Duration of fermentation affects microbiome composition and biological activity of an Indian traditional formulation - Panchagavya.

OBJECTIVE: This study aimed at investigating whether the duration of fermenting Panchagavya (PG) preparation in copper vessel affects its biological activity and microbiome composition. MATERIALS AND METHODS: Prophylactic potential of PG against bacterial infection was assessed through an in vivo assay employing the nematode worm Caenorhabditis elegans as a model host. Bacterial diversity of the PG samples was revealed through metagenomic analysis. RESULTS: Duration of fermentation was found to affect biological activity as well as microbiome composition of the PG samples. PG-samples fermented ≥60 min lost their prophylactic potential, and develop anthelmintic activity. Bacterial phyla whose relative abundance was significantly different between the prophylactic and anthelmintic PG samples were Planctomycetota, Proteabacteria, Bacteroidota, Verrucomicrobiota, Patescibacteria, Acidobacteriota, Chloroflexi, Firmicutes and Campilobacterota. CONCLUSION: This study validates the prophylactic potential of Panchagavya against bacterial pathogens, and shows that duration of the fermentation time while preparing PG can have profound effect on its biological activities. Biological activities of PG samples seem to have a correlation with their inherent microbial community. Metagenomic profiling can be an effective tool for standardization of PG formulations.

Intestinal Histopathological Aberrations in Oreochromis niloticus Juveniles upon Dietary Florfenicol Administration.

The aquaculture use of antibiotics can cause detrimental effects on fish organs and gut microbial dysbiosis. The impact of florfenicol (FFC) on fish intestinal histology, an approved antibiotic, remains unclear. This study aimed to investigate the effects of FFC on Oreochromis niloticus juveniles by administering FFC at 10 mg and 30 mg/kg biomass/day for 30 consecutive days to mimic long-term use. A dose-dependent reduction in feed intake, survival and biomass, with an upsurge in mortalities was observed. Even the therapeutic dose instigated mortalities on day 30 of FFC dosing (FD). Histopathological analysis revealed mild to moderate alterations, including loss of absorptive regions, epithelial degeneration, necrotized areas, intercellular enterocytic space and swollen laminar propria. Post-dosing, the observation of the detachment of lamina propria from the epithelium indicated imminent irritability. Goblet cells reduced drastically on day 30 FD, accompanied by an increase in intraepithelial lymphocytes. However, cessation of dosing for 13 days resulted in the reclamation of goblet cells and absorptive regions, indicating that the intestinal tissues underwent considerable repair after lifting antibiotic pressure. These findings suggested that O. niloticus can tolerate dietary FFC but emphasize the need for responsible use of antibiotics in aquaculture.

Multifactorial genetic control and magnesium levels govern the production of a Streptomyces antibiotic with unusual cell density dependence.

Streptomyces bacteria are renowned both for their antibiotic production capabilities and for their cryptic metabolic potential. Their metabolic repertoire is subject to stringent genetic control, with many of the associated biosynthetic gene clusters being repressed by the conserved nucleoid-associated protein Lsr2. In an effort to stimulate new antibiotic production in wild Streptomyces isolates, we leveraged the activity of an Lsr2 knockdown construct and successfully enhanced antibiotic production in the wild Streptomyces isolate WAC07094. We determined that this new activity stemmed from increased levels of the angucycline-like family member saquayamycin. Saquayamycin has both antibiotic and anti-cancer activities, and intriguingly, beyond Lsr2-mediated repression, we found saquayamycin production was also suppressed at high density on solid or in liquid growth media; its levels were greatest in low-density cultures. This density-dependent control was exerted at the level of the cluster-situated regulatory gene sqnR and was mediated in part through the activity of the PhoRP two-component regulatory system, where deleting phoRP led to both constitutive antibiotic production and sqnR expression. This suggests that PhoP functions to repress the expression of sqnR at high cell density. We further discovered that magnesium supplementation could alleviate this density dependence, although its action was independent of PhoP. Finally, we revealed that the nitrogen-responsive regulators GlnR and AfsQ1 could relieve the repression exerted by Lsr2 and PhoP. Intriguingly, we found that this low density-dependent production of saquayamycin was not unique to WAC07094; saquayamycin production by another wild isolate also exhibited low-density activation, suggesting that this spatial control may serve an important ecological function in their native environments.IMPORTANCEStreptomyces specialized metabolic gene clusters are subject to complex regulation, and their products are frequently not observed under standard laboratory growth conditions. For the wild Streptomyces isolate WAC07094, production of the angucycline-family compound saquayamycin is subject to a unique constellation of control factors. Notably, it is produced primarily at low cell density, in contrast to the high cell density production typical of most antibiotics. This unusual density dependence is conserved in other saquayamycin producers and is driven by the pathway-specific regulator SqnR, whose expression is influenced by both nutritional and genetic elements. Collectively, this work provides new insights into an intricate regulatory system governing antibiotic production and indicates there may be benefits to including low-density cultures in antibiotic screening platforms.

Simultaneous effect of medicinal plants as natural photosensitizers and low-level laser on photodynamic inactivation.

Photodynamic inactivation (PDI) technology is a promising alternative to antibiotics. This technology is defined as the inhibition of bacterial growth with photosensitizers while irradiated with low-level laser light in the wavelength of 532 ± 2.08 nm. A challenging area in this field is selecting photosensitizers with antibacterial potential. In this paper, to enhance the antibacterial efficiency, the photosensitizers (the selected plant extracts) with a high absorption peak at the selected laser frequency, 532 nm, were prepared. Low-concentration ethanolic plant extracts of Hibiscus sabdariffa and Opuntia ficus-indica were found to exhibit significant antibacterial activity against, Acinetobacter baumannii ATCC 19606 and, Staphylococcus aureus ATCC 33591 as two important human pathogenic bacteria. The effectiveness of these natural photosensitizers was measured by determining their Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values and by performing a time-killing assay in the absence and the presence of laser irradiation. Our results showed that the combination of low-level laser irradiation and the selected photosensitizers had excellent potential for treating in vitro bacterial infections. Therefore, PDI technology has great potential as a viable alternative to traditional antibiotics for combating bacterial infections. This study presents a promising avenue for further exploration of PDI and the use of laser technology in medical science.

Green Synthesis of Metal-Doped ZnO Nanoparticles Using Bauhinia racemosa Lam. Extract and Evaluation of Their Photocatalysis and Biomedical Applications.

A fascinating problem in the fields of nanoscience and nanobiotechnology has recently emerged, and to tackle this, the production of metal oxide nanoparticles using plant extracts offers numerous benefits over traditional physicochemical methods. In the present investigation, ZnO nanoparticles were fabricated from Bauhinia racemosa Lam. (BR) leaves extract with various transition metal (TM) dopants (Ni, Mn, and Co). Plant leaves extract containing metal nitrate solutions were utilized as a precursor to synthesize the pristine and TM-doped ZnO nanoparticles. Structural, functional, optical, and surface properties of the fabricated samples were studied by using physicochemical and photoelectrochemical measurements. The organic pollutants tetracycline (TC), ampicillin (AMP), and amoxicillin (AMX) were used in the photocatalytic degradation assessment of the fabricated samples. Through X-ray diffraction (XRD) and transmission electron microscopy (TEM) investigation, the fabricated nanoparticles wurtzite crystal structure was verified. Moreover, Fourier transform infrared (FT-IR) analysis verified the existence of functional groups in the fabricated nanoparticles. The migration of electrons from the deep donor level and zinc interstitial to the Zn-defect and O-defect is related to the emission peaks seen at 468, 480, 534, and 450 nm in photoluminescence (PL) spectra. Co-ZnO nanoparticles demonstrated potent and excellent photocatalytic degradation performance for TC (91.09%), AMP (87.97%), and AMX (92.42%) antibiotics within 210, 180, and 150 min of visible light irradiation. Co-ZnO nanoparticles also demonstrated strong antimicrobial performance against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Aspergillus flavus, Aspergillus niger, and Bacillus subtilis. Further investigation of in vitro cytotoxic potential against the A549 cell line (IC50 = 24 ± 0.5 µg/mL) utilizing MTT assay and the free radical scavenging performance of Co-ZnO nanoparticles estimated by DPPH assay utilizing l-ascorbic acid as a reference was also performed. Anti-inflammatory potential is also reviewed by comparing it with the standard drug Diclofenac, and the maximum activity was obtained for Ni-ZnO nanoparticles (IC50 = 72.4 µg/mL).

Mechanisms of Antibiotic Resistance and Developments in Therapeutic Strategies to Combat Klebsiella pneumoniae Infection.

Infections with drug-resistant bacteria have become one of the greatest public health challenges, and K. pneumoniae is among the top six drug-resistant bacteria. K. pneumoniae often causes nosocomial infections, leading to illnesses such as pneumonia, liver abscesses, soft tissue infections, urinary tract infections, bacteremia, and in some cases death. As the pathogen continues to evolve and its multidrug resistance increases, K. pneumoniae poses a direct threat to humans. Drug resistance in K. pneumoniae may occur due to the formation of biofilms, efflux pumps, and the production of ß-lactamases. In many cases, resistance is further enhanced by enzymatic modification and loss of porins. Drug resistance to K. pneumoniae has led to a decline in the effectiveness of conventional therapies against this pathogen. Therefore, there is an urgent need to accelerate the development of new antibiotics and explore new therapeutic approaches such as antimicrobial peptides, phages, traditional Chinese medicine, immunotherapy, Antimicrobial nanoparticle technology, antisense oligonucleotides and gene editing technologies. In this review, we discuss the mechanisms of drug resistance in K. pneumoniae and compare several new potential therapeutic strategies to overcome drug resistance in the treatment of K. pneumoniae infections.

Phytochemical Evaluation of Terminalia canescens DC. Radlk. Extracts with Antibacterial and Antibiotic Potentiation Activities against Selected ß-Lactam Drug-Resistant Bacteria.

Terminalia canescens DC. Radlk. (family: Combretaceae) is native to northern Australia. Species of the genus Terminalia are widely used as traditional medicines to treat diverse ailments, including bacterial infections. However, we were unable to find any studies that had examined the antimicrobial activity of T. canescens. In this study, T. canescens was screened against a panel of bacterial pathogens, including multi-antibiotic-resistant strains. Solvents with different polarities were used to extract different complements of phytochemicals from T. canescens leaves. Methanolic and aqueous extracts exhibited substantial antimicrobial activity against various pathogens, including those that are multidrug-resistant strains. When combined with some selected clinical antibiotics, some extracts potentiated the antibacterial inhibitory activity. This study identified two synergistic, eleven additive, eleven non-interactive and eight antagonistic interactions. The toxicities of the plant extracts were examined in the Artemia franciscana nauplii assay and were found to be non-toxic, except the aqueous extract, which showed toxicity. Metabolomic liquid chromatography-mass spectrometry (LC-MS) analyses highlighted and identified several flavonoids, including vitexin, quercetin, orientin and kaempferol, as well as the tannins ellagic acid and pyrogallol, which may contribute to the antibacterial activities observed herein. The possible mechanism of action of these extracts was further explored in this study.

Genome-resolved metagenomics of Venice Lagoon surface sediment bacteria reveals high biosynthetic potential and metabolic plasticity as successful strategies in an impacted environment.

Bacteria living in sediments play essential roles in marine ecosystems and deeper insights into the ecology and biogeochemistry of these largely unexplored organisms can be obtained from 'omics' approaches. Here, we characterized metagenome-assembled-genomes (MAGs) from the surface sediment microbes of the Venice Lagoon (northern Adriatic Sea) in distinct sub-basins exposed to various natural and anthropogenic pressures. MAGs were explored for biodiversity, major marine metabolic processes, anthropogenic activity-related functions, adaptations at the microscale, and biosynthetic gene clusters. Starting from 126 MAGs, a non-redundant dataset of 58 was compiled, the majority of which (35) belonged to (Alpha- and Gamma-) Proteobacteria. Within the broad microbial metabolic repertoire (including C, N, and S metabolisms) the potential to live without oxygen emerged as one of the most important features. Mixotrophy was also found as a successful lifestyle. Cluster analysis showed that different MAGs encoded the same metabolic patterns (e.g., C fixation, sulfate oxidation) thus suggesting metabolic redundancy. Antibiotic and toxic compounds resistance genes were coupled, a condition that could promote the spreading of these genetic traits. MAGs showed a high biosynthetic potential related to antimicrobial and biotechnological classes and to organism defense and interactions as well as adaptive strategies for micronutrient uptake and cellular detoxification. Our results highlighted that bacteria living in an impacted environment, such as the surface sediments of the Venice Lagoon, may benefit from metabolic plasticity as well as from the synthesis of a wide array of secondary metabolites, promoting ecosystem resilience and stability toward environmental pressures. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00192-z.

Gramine sensitizes Klebsiella pneumoniae to tigecycline killing.

BACKGROUND: The presence of plasmid-mediated resistance-nodulation-division (RND) efflux pump gene cluster tmexCD1-toprJ1 and its related variants has been associated with heightened resistance to tigecycline, thus diminishing its effectiveness. In this study, we explored the potential of gramine, a naturally occurring indole alkaloid, as an innovative adjuvant to enhance the treatment of infections caused by K. pneumoniae carrying tmexCD-toprJ-like gene clusters. METHODS: The synergistic potential of gramine in combination with antibiotics against both planktonic and drug-tolerant multidrug-resistant Enterobacterales was evaluated using the checkerboard microbroth dilution technique and time-killing curve analyses. Afterwards, the proton motive force (PMF) of cell membrane, the function of efflux pump and the activity of antioxidant system were determined by fluorescence assay and RT-PCR. The intracellular accumulation of tigecycline was evaluated by HPLC-MS/MS. The respiration rate, bacterial ATP level and the NAD+/NADH ratio were investigated to reveal the metabolism state. Finally, the safety of gramine was assessed through hemolytic activity and cytotoxicity assays. Two animal infection models were used to evaluate the in vivo synergistic effect. RESULTS: Gramine significantly potentiated tigecycline and ciprofloxacin activity against tmexCD1-toprJ1 and its variants-positive pathogens. Importantly, the synergistic activity was also observed against bacteria in special physiological states such as biofilms and persister cells. The mechanism study showed that gramine possesses the capability to augment tigecycline accumulation within cells by disrupting the proton motive force (PMF) and inhibiting the efflux pump functionality. In addition, the bacterial respiration rate, intracellular ATP level and tricarboxylic acid cycle (TCA) were promoted under the treatment of gramine. Notably, gramine effectively restored tigecycline activity in multiple animal infection models infected by tmexCD1-toprJ1 positive K. pneumoniae (RGF105-1). CONCLUSION: This study provides the first evidence of gramine's therapeutic potential as a novel tigecycline adjuvant for treating infections caused by K. pneumoniae carrying tmexCD-toprJ-like gene clusters.

Impact of the ´Alforja Educativa' on Ecuadorian schoolchildren's knowledge of bacteria, antibiotics, and antibiotic resistance, a pretest-posttest study.

BACKGROUND: Widespread use of antibiotics disrupts the balance in the microbial world and promotes development and spread of antibiotic resistant bacteria. Educational initiatives are important as part of strategies to mitigate antibiotic resistance. The Alforja Educativa is an innovative educational program developed in Ecuador with the aim to teach schoolchildren about antibiotic use and antibiotic resistance. The program places antibiotic resistance within a broader frame of health, well-being, and ecological awareness, highlighting the importance to maintain balance in the microbial world. The objective of this study was to evaluate the effect of the Alforja Educativa on knowledge about bacteria, antibiotics and antibiotic resistance amongst fifth and sixth grade Ecuadorian schoolchildren. METHODS: This pretest-posttest intervention study was conducted between April and June 2017 and comprised fifth and sixth grade schoolchildren from 20 schools in Cuenca, Ecuador, recruited by purposeful sampling. The Alforja Educativa was implemented over twelve 80-minute sessions by trained university students. Schoolchildren's knowledge was assessed before and after participation in the educational program using a structured questionnaire. A mean total score, the proportion of correct responses for each individual knowledge-based question, as well as correct responses for each of the multiple-choice options of the knowledge-based questions were calculated for the pretest and posttest. RESULTS: A total of 1,257 schoolchildren participated in the Alforja Educativa program, of which 980 (78%) completed both the pretest and posttest. Overall, the mean total knowledge score increased from pretest to posttest (2.58/7.00 vs. 3.85/7.00; CI = 0.5, p < 0.001). After participation in the program, the proportion of schoolchildren that correctly identified that bacteria can be both good and bad increased from 35.0 to 84.3%. In addition, scores increased for correctly identifying the meaning of antibiotic resistance (37.4-72.0%); how to prevent antibiotic resistance (63.2-74.6%); and for identifying the meaning of self-medication (46.3-54.3%). CONCLUSION: The Alforja Educativa was effective in improving the knowledge of participating schoolchildren about concepts related to bacteria, antibiotics and antibiotic resistance. The holistic perspective taken to explain the complex relationship between humans and bacteria, as well as the effect of antibiotics on the microbial world, may help provide a foundation for more sustainable antibiotic use.

Sports and sustainable development: the troubling absence of meat sourcing policies in the sports sector.

The excessive use of antibiotics in industrial meat production in the U.S. incurs severe health implications for animals, humans, and the environment, thereby threatening the integrated health of the ecosystem and sustainable development. While the consumption of meat, including hot dogs, chicken wings, and hamburgers, is a hallmark of attending professional sports events in North America, the sourcing policies for meat in the realm of professional sports remain relatively obscure. We conducted a content analysis case study on the four major sports leagues in North America, their teams and stadium practices. Our objective was twofold: first, to investigate existing sustainability initiatives at the league, team, and stadium levels; and second, to examine whether there are any food sourcing programs, specifically meat sourcing policies that might encourage the consumption of meat produced without the use of antibiotics, in the sports sector that are designed to mitigate ecological ramifications of meat consumption within sports contexts. Results show that existing sustainability initiatives at the three levels are focused primarily on reducing carbon emissions and waste. There is, however, a notable neglect of food sourcing policies, which is concerning given that industrial animal agriculture is a leading cause of antibiotic resistance and environmental degradation. This suggests that meat sourcing policy is a missing piece in current sustainability initiatives. The major sports leagues should therefore consider incorporating pertinent policies, such as procuring meat-based products produced without the use of antibiotics to help strengthen their existing efforts in achieving their sustainable development goals.

A combined strategies intervention on the World Health Organization prescribing indicators: A quasi-randomised trial.

BACKGROUND: Irrational medicine use is a global problem that may potentiate antimicrobial resistance. AIM: This study aims to assess prescribing practices and the effect of a prescription audit and feedback coupled with small-group education intervention on prescribing indicators. SETTING: The study was conducted in public-sector healthcare facilities in Eswatini. METHODS: A cluster quasi-randomised controlled study was conducted from 2016 to 2019 using the World Health Organization/ International Network for Rational Use of Drugs (WHO/INRUD) prescribing indicators at baseline, post-intervention and post-follow-up. A 6-month unblinded intervention was tested in 32 healthcare facilities, randomly allocated to intervention (16) and control (16) arms. Prescribing practices were assessed post-intervention, and 6 months after the intervention, through an audit of 100 randomly selected prescriptions from each facility. Comparisons of WHO or INRUD prescribing indicators were conducted using the intention-to-treat analysis at the two times. RESULTS: At baseline, in both arms, rational prescribing standards were met by the number of medicines per prescription and the use of injections. Antibiotic use was above 50% in both arms. After adjustment for baseline antibiotics use, region and level of care, there were no significant differences in all prescribing indicators between the two arms, post-intervention and at 6 months follow-up. CONCLUSION: In a lower middle-income setting with a high prevalence of irrational prescribing practices, a prescription audit, feedback and small-group education intervention had no benefits in improving rational prescribing.Contribution: Multifaceted strategies, strengthening of pharmacy and therapeutics committees, and holistic monitoring of medicine use are recommended to promote rational medicine use.

The effects and mechanisms of natural products on Helicobacter pylori eradication.

Helicobacter pylori (H. pylori) eradication is pivotal for alleviating gastric mucosal inflammation and preventing the progression of gastric diseases. While antibiotic-based therapies have achieved significant success in H. pylori eradication, challenges such as antibiotic resistance, drug toxicity, side effects, nonadherence, inapplicability, and disruption of gastrointestinal microflora have emerged. Updated therapies are urgently needed to suppress H. pylori. Nature has provided multitudinous therapeutic agents since ancient times. Natural products can be a potential therapy endowed with H. pylori eradication efficacy. We summarize the basic information, possible mechanisms, and the latest research progress of some representative natural products in H. pylori eradication, highlighting their safety, accessibility, efficiency, and ability to overcome limitations associated with antibiotic application. This review highlights the potential therapeutic advantages of incorporating ethnomedicine into anti-H. pylori regimens. The findings of this review may provide insights into the development of novel natural products and expand the therapeutic options available for H. pylori eradication.

Relationship between biofilm formation and antibiotic resistance of Klebsiella pneumoniae and updates on antibiofilm therapeutic strategies.

Klebsiella pneumoniae is a Gram-negative bacterium within the Enterobacteriaceae family that can cause multiple systemic infections, such as respiratory, blood, liver abscesses and urinary systems. Antibiotic resistance is a global health threat and K. pneumoniae warrants special attention due to its resistance to most modern day antibiotics. Biofilm formation is a critical obstruction that enhances the antibiotic resistance of K. pneumoniae. However, knowledge on the molecular mechanisms of biofilm formation and its relation with antibiotic resistance in K. pneumoniae is limited. Understanding the molecular mechanisms of biofilm formation and its correlation with antibiotic resistance is crucial for providing insight for the design of new drugs to control and treat biofilm-related infections. In this review, we summarize recent advances in genes contributing to the biofilm formation of K. pneumoniae, new progress on the relationship between biofilm formation and antibiotic resistance, and new therapeutic strategies targeting biofilms. Finally, we discuss future research directions that target biofilm formation and antibiotic resistance of this priority pathogen.

Thermal-Accelerated Urease-Driven Bowl-Like Polydopamine Nanorobot for Targeted Photothermal/Photodynamic Antibiotic-Free Antibacterial Therapy.

The problem of antibiotic resistance seriously affects the treatment of bacterial infections, so there is an urgent need to develop novel antibiotic-independent antimicrobial strategies. Herein, a urease-driven bowl-like mesoporous polydopamine nanorobot (MPDA@ICG@Ur@Man) based on single-wavelength near-infrared (NIR) remote photothermal acceleration to achieve antibiotic-free phototherapy(photothermal therapy, PTT, plus photodynamic therapy, PDT) is first reported. The smart nanorobots can perform active movement by decomposing urea to produce carbon dioxide and ammonia. Particularly, the elevated local temperature during PTT can increase urease activity to enhance the autonomous movement and thus increase the contact between the antimicrobial substance and bacteria. Compared with a nanomotor propelled by urea only, the diffusion coefficient (De) of photothermal-accelerated nanorobots is increased from 1.10 to 1.26 µm2 s-1. More importantly, urease-driven bowl-like nanorobots with photothermal enhancement can specifically identify Escherichia coli (E. coli) and achieve simultaneous PTT/PDT at a single wavelength with 99% antibactericidal activity in vitro. In a word, the urease-driven bowl-like nanorobots guided by photothermal-accelerated strategy could provide a novel perspective for increasing PTT/PDT antibacterial therapeutic efficacy and be promising for various antibiotic-free sterilization applications.