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Reversal Potential of Multidrug Antibiotic Resistance in Cutibacterium acnes by Ethanol Extracts of Rhubarb

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ABSTRACTCutibacterium acnes (C. acnes) is a major contributor to acne inflammation and exhibits significant antibiotic resistance, but research focusing on reversing this resistance is limited. Rhubarb, a natural plant with known therapeutic effects, shows potential in combating antibiotic resistance, however, no studies have been explored before. The aim of this study was to investigate rhubarb's ability to reverse antibiotic resistance in C. acnes. Strains 11,827 and 6919 were cultured and passaged with 0.019 μg/mL ethanol extract, and antibiotic sensitivity was monitored from passage 0 to 12. The extract effectively reversed antibiotic resistance, and was also confirmed by growth curves and oxidative markers. The impact varied across antibiotics, with the most significant reversal being erythromycin (1000‐fold), followed by clindamycin (250‐fold), and a weaker effect for tetracycline (2–4‐fold). This suggests that the extract has a stronger reversal effect on antibiotics with higher resistance. LC‐MS analysis identified flavonoids and heterocyclic compounds were may be key active components, with (‐)‐epicatechin being the most abundant and crucial for antibacterial and reversal activities. The study suggests a new strategy of using rhubarb ethanol extract as a promising acne treatment with much lower resistance, with vital advantages over conventional antibiotics. These also provide new insights into using herbal plants to combat antibiotic resistance.

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  • Research Article
  • Cite Count Icon 1
  • 10.5897/jidi.9000009
Assessing the frequency and antibiotic resistance of nosocomial bacterial infections in the intensive care units and general wards
  • Aug 31, 2011
  • Journal of Infectious Diseases and Immunity
  • Kiumars Ahmadi + 2 more

Considering the perpetual existence of resistant bacteria in different wards of hospitals, particularly the intensive care unit (ICU), as well as the hindrance they cause against therapy make it necessary to have comprehensive knowledge of these bacteria and their respective pattern of antibiotic resistance in different communities. This study was conducted to determine the pattern of antibiotic resistance for common bacteria in general wards and the intensive care unit of our hospital. This is a cross-sectional, descriptive study conducted from October 2009 through October 2010, in Madaen Hospital, Tehran. Standard sampling was performed for biologic fluids, wounds and devices associated with patients such as nozzle of the suction unit, endotracheal tube, central venous pressure catheter etc. A total number of 692 samples were administered to the microbiology department of the hospital, to be cultured on selective and then differential media. Once the bacteria were distinguished, their sensitivity for antibiotics was studied. From the total of 692 specimens, 192 pertained to patients in the intensive care unit, and 500 were obtained from patients in the general wards. Gram positive bacteria and fungi were more frequent in the ICU, whereas Gram negative bacteria were more frequently found in the general wards (p=0.001). The most common bacteria found in the ICU and general wards wereKlebsiella (22.4%) and Escherichia coli (31.6%), respectively. In the ICU, the most frequent resistance was observed against Ceftazidime (87.9%), while the lowest resistance was against Vancomycin (7.7%). In general wards, Ceftriaxone indicated the greatest resistance (78.6%), with Vancomycin having the lowest resistance observed (9%). The antibiotic resistance against most antibiotics was significantly higher in the ICU compared to general wards (p=0.01). The findings of this study indicate that many Gram positive and negative bacteria are frequently encountered in the ICU. In addition, antibiotic resistance, particularly multi-drug resistance, is frequent among microorganisms of the ICU, as well as the general wards. Key words: Intensive care unit, general ward, bacterial infection, antibiotic resistance.

  • Research Article
  • 10.12928/pharmaciana.v15i1.27466
Formulation of a sheet mask essence incorporating Betel leaf (Piper betle L.) ethanol extract and its antibacterial efficacy against Propionibacterium acnes
  • Mar 21, 2025
  • Pharmaciana
  • Annisa Dyah Wulandari + 2 more

Betel leaf (Piper betle L.) encompasses a multitude of bioactive constituents, including tannins, saponins, flavonoids, alkaloids, and terpenoids, which possess significant antibacterial properties. An ethanol extract derived from betel leaf was meticulously formulated and assessed for its potential as an antibacterial agent specifically targeting Propionibacterium acnes, a bacterium associated with the etiology of acne. This investigation was undertaken with the aim of mitigating the antibiotic resistance commonly observed with traditional acne therapies. The ethanol extract of betel leaf was incorporated into a sheet mask essence, resulting in the development of four distinct formulations (F0, F1, F2, and F3), which were subsequently subjected to comprehensive evaluations of their physical quality and stability. The formulation exhibiting optimal physical characteristics and stability was further scrutinized for its antibacterial efficacy against Propionibacterium acnes. The antibacterial performance of the selected formulation was benchmarked against a positive control comprising a sheet mask infused with clindamycin gel, as well as another containing tea tree oil. Empirical results identified Formula 2, containing 1.5% ethanol extract of betel leaf, as the most efficacious formulation. Formula 2 demonstrated pronounced antibacterial activity against Propionibacterium acnes, with an inhibitory zone measuring 24.67 mm. Although this inhibitory zone was slightly less extensive than that produced by the clindamycin gel sheet mask (32.00 mm), it was comparable to the tea tree oil sheet mask, which exhibited an inhibitory zone of 23.00 mm. In conclusion, the selected sheet mask formulation (Formula 2) exhibits significant antibacterial activity against Propionibacterium acnes, surpassing the efficacy of commercially available tea tree oil sheet masks, thereby presenting a promising alternative for acne management with a diminished risk of promoting antibiotic resistance.

  • Research Article
  • 10.36858/ipj.v2i1.42
ANTIBACTERIAL ACTIVITY OF 50% AND 96% ETHANOL EXTRACT OF HORN BANANA PEEL (Musa acuminata x Musa balbisiana) AGAINST Propionibacterium acnes
  • Jan 31, 2025
  • Indonesian Pharmacopeia Journal
  • Vanisa Al Maghfiro + 2 more

Propionibacterium acnes is the main bacterium responsible for acne, with over 50% of its strains resistant to synthetic drugs. Treatment with natural substances, such as horn banana peel extract, can be an alternative. The polarity of the solvent, influenced by ethanol concentration, affects the compounds extracted and their antibacterial activity. This study aims to identify secondary metabolite compounds in 50% and 96% ethanol extracts of horn banana peel, evaluate the antibacterial activity of both extracts against Propionibacterium acnes, and determine the differences in antibacterial activity based on variations in solvent concentration. The banana peel extract was obtained using the Microwave Assisted Extraction (MAE) method. Phytochemical screening was conducted using the tube test method. Antibacterial activity was assessed using the well diffusion method. The 50% ethanol extract of horn banana peel had a higher yield (16,12%) compared to the 96% ethanol extract (10,02%). Both extracts contained active compounds such as alkaloids, flavonoids, tannins, polyphenols, and saponins. The 50% ethanol extract at concentrations of 5%, 10%, and 15% exhibited greater antibacterial activity against Propionibacterium acnes, with average inhibition zones of 18,68±1,32 mm, 14,11±0,35 mm, and 11.07±0.32 mm, respectively. In contrast, the 96% ethanol extract showed average inhibition zone diameters of 15,17±1,33 mm, 11,35±0,92 mm, and 8,06±0,86 mm. The differences in antibacterial activity are believed to be due to the varying polarities of the two solvents, with 50% ethanol being the more polar solvent. Two-way ANOVA analysis revealed a significant difference between the two factors (ethanol concentration and extract concentration) concerning the inhibition zones (p-value 0,004). The results indicate that both 50% and 96% ethanol extracts of horn banana peel contain secondary metabolite compounds such as alkaloids, flavonoids, tannins, polyphenols, and saponins. Both extracts exhibit antibacterial activity against Propionibacterium acnes, with a significant difference in activity between the 50% and 96% ethanol extracts.

  • Research Article
  • Cite Count Icon 48
  • 10.4103/0019-5154.174025
Cross-sectional Pilot Study of Antibiotic Resistance in Propionibacterium Acnes Strains in Indian Acne Patients Using 16S-RNA Polymerase Chain Reaction: A Comparison Among Treatment Modalities Including Antibiotics, Benzoyl Peroxide, and Isotretinoin
  • Jan 1, 2016
  • Indian Journal of Dermatology
  • Kabir Sardana + 4 more

Background:Antibiotic resistance is a worldwide problem in acne patients due to regional prescription practices, patient compliance, and genomic variability in Propionibacterium acnes, though the effect of treatment on the resistance has not been comprehensively analyzed.Aims:Our primary objective was to assess the level of antibiotic resistance in the Indian patients and to assess whether there was a difference in the resistance across common treatment groups.Subjects and Methods:A cross-sectional, institutional based study was undertaken and three groups of patients were analyzed, treatment naïve, those on antibiotics and patients on benzoyl peroxide (BPO) and/isotretinoin. The follicular content was sampled and the culture was verified with 16S rRNA polymerase chain reaction, genomic sequencing, and pulsed-field gel electrophoresis. Minimum inhibitory concentration (MIC) assessment was done for erythromycin (ERY), azithromycin (AZI), clindamycin (CL), tetracycline (TET), doxycycline (DOX), minocycline (MINO), and levofloxacin (LEVO). The four groups of patients were compared for any difference in the resistant strains.Results:Of the 52 P. acnes strains isolated (80 patients), high resistance was observed to AZI (100%), ERY (98%), CL (90.4%), DOX (44.2%), and TETs (30.8%). Low resistance was observed to MINO (1.9%) and LEVO (9.6%). Statistical difference was seen in the resistance between CL and TETs; DOX/LEVO and DOX/MINO (P < 0.001). High MIC90 (≥256 μg/ml) was seen with CL, macrolides, and TETs; moreover, low MIC90 was observed to DOX (16 μg/ml), MINO (8 μg/ml), and LEVO (4 μg/ml). Though the treatment group with isotretinoin/BPO had the least number of resistant strains there was no statistical difference in the antibiotic resistance among the various groups of patients.Conclusions:High resistance was seen among the P. acnes strains to macrolides-lincosamides (AZI and CL) while MINO and LEVO resistance was low.

  • Research Article
  • Cite Count Icon 99
  • 10.1039/c1em10634a
Occurrence of antibiotic resistance and characterization of resistance genes and integrons in Enterobacteriaceae isolated from integrated fish farms in south China
  • Jan 1, 2011
  • Journal of Environmental Monitoring
  • Hao-Chang Su + 5 more

Antibiotics are still widely applied in animal husbandry to prevent diseases and used as feed additives to promote animal growth. This could result in antibiotic resistance to bacteria and antibiotic residues in animals. In this paper, Enterobacteriaceae isolated from four integrated fish farms in Zhongshan, South China were tested for antibiotic resistance, tetracycline resistance genes, sulfonamide resistance genes, and class 1 integrons. The Kirby-Bauer disk diffusion method and polymerase chain reaction (PCR) assays were carried out to test antibiotic susceptibility and resistance genes, respectively. Relatively high antibiotic resistance frequencies were found, especially for ampicillin (80%), tetracycline (52%), and trimethoprim (50%). Out of 203 Enterobacteriaceae isolates, 98.5% were resistant to one or more antibiotics tested. Multiple antibiotic resistance (MAR) was found highest in animal manures with a MAR index of 0.56. Tetracycline resistance genes (tet(A), tet(C)) and sulfonamide resistance genes (sul2) were detected in more than 50% of the isolates. The intI1 gene was found in 170 isolates (83.7%). Both classic and non-classic class 1 integrons were found. Four genes, aadA5, aadA22, dfr2, and dfrA17, were detected. To our knowledge, this is the first report for molecular characterization of antibiotic resistance genes in Enterobacteriaceae isolated from integrated fish farms in China and the first time that gene cassette array dfrA17-aadA5 has been detected in such fish farms. Results of this study indicated that fish farms may be a reservoir of highly diverse and abundant antibiotic resistant genes and gene cassettes. Integrons may play a key role in multiple antibiotic resistances posing potential health risks to the general public and aquaculture.

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  • Cite Count Icon 1
  • 10.1007/s42770-024-01590-w
Pioneering study of Egyptian Neem and Jojoba extracts with molecular docking combat hospital multidrug resistant bacteria.
  • Jan 8, 2025
  • Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]
  • Toka Khairy + 6 more

Hospital surfacesare often contaminatedwith multidrug-resistant pathogenic bacteria that cause healthcare-associated infections and lead to increased mortality and morbidity. Thereis a need for new alternative antibacterial agents to overcome antibiotic resistance. Azadirachta indica and Simmondsia chinensis have been found to possess antibacterial activity and medicinal value. The antibacterial activity of these plant extracts against clinical isolates was investigated using the agar disc diffusion method. These clinical isolates included E. coli, Pseudomonas aeruginosa, Acinetobacter spp., Klebsiella pneumoniae, Stenotrophomonas maltophilia, and methicillin-resistant Staphylococcus aureus (MRSA), which were identified by the vitek-2 system, and resistance genes of selected bacterial strains were identified by using the bioFire FilmArray test. The most potent extract of these plants was the ethanolic extract, where the inhibition percentage of ethanolic Jojoba and Neem extracts was 90.9% and 74.5%, respectively against all the tested pathogens. On the other hand, the methanolic extracts of Neem and Jojoba have different degrees of antibacterial activity against the tested pathogens. The phytochemical components of the most potent extracts (ethanolic extracts) were investigated by gas chromatography‒mass spectrometry (GC\MS), which revealed that the ethanolic extracts were enriched in phenolics, flavonoids, and sugars. FTIR analyses of the plant extracts confirmed the presence of alcoholic, carboxylic, and aldehydic moieties. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity of the ethanolic extracts of Neem and Jojoba increased in a dose-dependent manner, with average IC50 values of 98.17 ± 0.85, 4.95 ± 0.06, and 4.17 ± 0.04 mg/mL, respectively, for the ethanolic Neem extract, the ethanolic Jojoba extract, and ascorbic acid (standard). Furthermore, increased cytotoxicity was demonstrated in the HFB4 cell line in a dose-dependent manner. The average IC50s of the ethanolic Neem extract and the ethanolic Jojoba extract were 18.18 ± 0.15 and 76.16 ± 1.49 mg/mL, respectively. Moreover, the results for the antibiofilm activity of the ethanolic Neem extract showed that 99.5% of the biofilms formed at 25 mg/ml. Inaddition, 50 mg/ml of the ethanolic extract of Jojoba had a suppressive effect of 98.2%. The significant components Nonanoic acid (21.9405%) and Palmitic Acid (16.0869%) from Neem and pinitol from Jojoba (82.85%) were selected throughout the molecular docking investigation, by which the chosen constituents inhibited the crystal structure of penicillin-binding protein 4 (PBP4) from Staphylococcus aureus (PDB ID: 1TVF) and the crystal structure of the OXA-48 beta-lactamase (PDB ID: 7AUX) from K. pneumoniae. Overall, our study reveals the effectiveness of antimicrobial plant extracts as therapeutic solutions for antibiotic resistance in Egypt and worldwide with some modifications to decrease their cytotoxicity.

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  • Research Article
  • Cite Count Icon 90
  • 10.1155/2016/2164761
Antibiotic Resistance of Diverse Bacteria from Aquaculture in Borneo.
  • Jan 1, 2016
  • International Journal of Microbiology
  • M M Kathleen + 6 more

The administration of antimicrobials in aquaculture provides a selective pressure creating a reservoir of multiple resistant bacteria in the cultured fish and shrimps as well as the aquaculture environment. The objective of this study was to determine the extent of antibiotic resistance in aquaculture products and aquaculture's surrounding environment in Sarawak, Malaysian Borneo. Ninety-four identified bacterial isolates constituted of 17 genera were isolated from sediment, water, and cultured organisms (fish and shrimp) in selected aquaculture farms. These isolates were tested for their antibiotic resistance against 22 antibiotics from several groups using the disk diffusion method. The results show that the highest resistance was observed towards streptomycin (85%, n = 20), while the lowest resistance was towards gentamicin (1.1%, n = 90). The multiple antibiotic resistant (MAR) index of the isolates tested ranged between 0 and 0.63. It was suggested that isolates with MAR index > 0.2 were recovered from sources with high risk of antibiotic resistant contamination. This study revealed low level of antibiotic resistance in the aquaculture bacterial isolates except for streptomycin and ampicillin (>50% resistance, n = 94) which have been used in the aquaculture industry for several decades. Antibiotic resistant patterns should be continuously monitored to predict the emergence and widespread of MAR. Effective action is needed to keep the new resistance from further developing and spreading.

  • Research Article
  • 10.22270/ujpr.v10i4.1393
EVALUATING THE SYNERGISTIC ACTIVITY OF ROSMARINUS OFFICINALIS EXTRACTS WITH ANTIBIOTICS AGAINST MDR BACTERIA
  • Sep 15, 2025
  • Universal Journal of Pharmaceutical Research
  • Najmaddin Hussein Ali Khalil + 1 more

Background: The rise of antimicrobial resistance and multidrug-resistant bacteria is growing global threat, particularly Pseudomonas aeruginosa and Klebsiella pneumoniae, has become a critical challenge in clinical microbiology and pharmacotherapy and even be untreatable with conventional antibiotics. Exploring plant-derived antimicrobial offers promising complementary strategies. Objective: This study evaluates the antibacterial activity of ethanolic and aqueous extracts of Rosmarinus officinalis and investigate the synergistic effect of the high effective concentration of ethanolic and aqueous extracts in combination with ceftazidime, cefoperazone and gentamycin against P. aeruginosa, and K. pneumoniae. Method: The dried leaves of rosemary were macerated in 96% ethanol and water to prepare ethanolic and aqueous extract and phytochemical screening was conducted to identify active constituents. Clinical MDR isolates were tested using agar well diffusion method. For synergy, ceftazidime, cefoperazone and gentamycin discs were immersed in 100% ethanolic and aqueous extracts separately and tested against MDR strains. Results: Ethanolic extract exhibited dose dependent antibacterial activity with maximum zones of inhibition at 100mg/ml: P. aeruginosa (7.50±0.50 mm), K. pneumoniae (6.00±0.20 mm). Aqueous extract showed negligible activity. Synergistic testing revealed enhanced inhibition zones when antibiotic discs were pre-treated with ethanolic extract. While aqueous extract showed decreasing in the inhibition zone. Conclusions: The 100 mg/ml ethanolic extract of R. officinalis enhances the efficacy of cefoperazone and gentamicin and no effect on ceftazidime. These findings indicate that rosemary extract could serve as potential adjunct in overcoming antibiotic resistance. Peer Review History: Received 7 June 2025; Reviewed 11 July 2025; Accepted 18 August; Available online 15 September 2025 Academic Editor: Dr. Emmanuel O. Olorunsola, Department of Pharmaceutics &amp; Pharmaceutical Technology, University of Uyo, Nigeria, olorunsolaeo@yahoo.com Reviewers: Dr. Areen Alshweiat, University of Szeged, Hungary, areen.alshweiat@hu.edu.jo Dr. Awofisayo, O Abosede, University of Uyo, Nigeria, shalomgirl08@yahoo.com

  • Research Article
  • Cite Count Icon 11
  • 10.1038/sj.embor.7400181
Overcoming resistance.
  • Jun 1, 2004
  • EMBO reports
  • Caroline Hadley

Overcoming resistance.

  • Research Article
  • Cite Count Icon 41
  • 10.1128/jb.00356-07
Novel Links between Antibiotic Resistance and Antibiotic Production
  • Mar 23, 2007
  • Journal of Bacteriology
  • Justin R Nodwell

Streptomyces coelicolor is the best-developed model system for an enormous family of filamentous soil bacteria. One reason for the interest in these organisms is that they produce numerous secondary metabolites, many of which are employed clinically as antibiotics. Most streptomycetes produce several biologically active secondary metabolites; S. coelicolor produces at least four. Not surprisingly, they also possess resistance genes for the antimicrobial molecules they produce; often these are linked to and are coregulated with the antibiotic biosynthesis genes. As our understanding of secondary metabolism advances, it is becoming increasingly clear that the relationship between antibiotic production and resistance is more complicated than expected. For example, the S. coelicolor genome encodes proteins that are similar in sequence and mechanism to those that confer clinical resistance to vancomycin (7, 8). This was a surprise because S. coelicolor does not produce vancomycin or, indeed, any glycopeptide antibiotics. More recently, environmental isolates of Streptomyces spp. have been described that harbor enzymatic resistance mechanisms for antibiotics that are semisynthetic or wholly synthetic and, presumably, have never existed in nature (5, 17). Where did the selective pressure for these resistance mechanisms come from? In addition to this apparent disconnect between biosynthesis and resistance, antibiotic production appears to be controlled by a regulatory network of truly Byzantine proportions: to date at least 18 genes have been shown to influence antibiotic production in S. coelicolor—a subset of these also control sporulation (3). Clearly, bacteria have devoted a great deal of evolutionary time to developing antibiotic resistance mechanisms and the regulatory apparatus for controlling for antibiotic production. In this issue of the Journal of Bacteriology, and in a companion article published in Molecular Microbiology (15), Kenji Nishimura and coworkers in Kozo Ochi's laboratory report the elucidation of the mechanism of type II streptomycin resistance (12). Their discoveries strongly reinforce the suspicion that there is much to learn about the relationship between antibiotic resistance and biosynthesis. Streptomycin, a secondary metabolite produced by several Streptomyces strains, was introduced as a therapeutic agent in the early 1940s and proved spectacularly successful against a number of serious infections. Sadly, however, it went on to set the pattern for clinical resistance to antibiotics. By 1946, resistant strains had been reported, and by the early 1950s, clinical resistance was so widespread that the antibiotic began to fall into disuse, supplanted as a miracle cure-all by newer drugs. In S. coelicolor, two categories of streptomycin-resistant mutants have been characterized. Type I mutants are resistant to high concentrations of the antibiotic, and type II mutants are resistant to much lower concentrations. Both mechanisms are specific to streptomycin; neither confers resistance to other antibiotics. This pattern of distinct high and low resistance has been reported for other bacteria (6, 11). An odd effect of both types of strR mutations on S. coelicolor is that they bring about the overproduction of the secondary metabolite actinorhodin, a polyketide that is otherwise unrelated to streptomycin (9, 13, 16). Indeed, strR mutations can overcome the effects of mutations in genes such as relA, relC, and brgA that, on their own, impair actinorhodin production (16). Type I resistance is brought about by mutations in the rpsL gene, which encodes the S12 protein of the 30S subunit of the ribosome (16). The mechanism responsible for type II resistance was first demonstrated to be genetically distinct from that of type I resistance in 1948 (6) but eluded molecular characterization until now. Nishimura and coworkers (12) have demonstrated its association with the gene rsmG in S. coelicolor and its orthologue gidB in Escherichia coli, Mycobacterium tuberculosis, and other species (15). This work linking rsmG to streptomycin resistance is of interest for technical reasons as well as biological ones. Genetic mapping is challenging in S. coelicolor and has apparently proven to be particularly difficult in this case. Reasons for this may be that the rsmG mutant phenotype is a relatively weak one and that most bacteria throw off type II streptomycin-resistant mutants at a relatively high frequency. The authors therefore made use of chip technology (1) recently developed for S. coelicolor, in which the entire genome sequence is arrayed in overlapping oligonucleotides. The arrays are interrogated by annealing them to wild-type and mutant chromosomal DNA, and the result is the straightforward identification of point mutations, insertions, or deletions within the mutant genome. In this case, the authors were able to show that a type II mutant had a sequence change in the S. coelicolor gene SCO3885, which they went on to rename rsmG for rRNA small subunit methyltransferase (12). This technology would likely be applicable to many organisms. For example, the identification of mutations that confer resistance to the diarylquinolone drug R207910 necessitated the nearly complete sequencing of three Mycobacterium sp. genomes (2). While high-throughput DNA sequencing grows increasingly efficient and affordable, it still requires a significant computational effort that could be avoided by this array technology. The rsmG gene encodes a highly conserved S-adenosylmethionine (SAM) binding protein and is found in all sequenced bacterial genomes. In spite of this high degree of conservation, the gene is nonessential: a deletion mutation confers type II streptomycin resistance and, in S. coelicolor, the overproduction of actinorhodin. This phenotype is associated with the loss of a specific 16S rRNA methylation at G518 in S. coelicolor (12) or G527 in E. coli (15), a residue that is found within the “530 loop” of the 16S rRNA and which interacts directly with streptomycin (4). Mutations in the M. tuberculosis orthologue of rsmG, gidB, were found to be tightly associated with type II streptomycin resistance in a large collection of clinical isolates (15). Previous work from the Ochi laboratory and others (10, 14, 16) demonstrated that type II mutants of S. coelicolor express SAM synthetase at higher levels than congenic wild-type strains (14). Consistent with this, they show here that an rsmG deletion mutant exhibits increased SAM synthetase activity late in the growth cycle and that this could be correlated with enhanced transcription of the SAM synthetase-encoding gene metK. An additional feature of this mutant is that translation was greatly enhanced in stationary phase cells relative to that a wild-type strain. This, however, was not caused by the elevated level of SAM synthetase or SAM levels as overexpression of metK from a high-copy-number plasmid did not confer enhanced translation in a wild-type strain. Enhanced translational efficiency may therefore be linked to the absence of 16S rRNA methylation. Overexpression of metK did, however, give rise to the overproduction of actinorhodin, as reported previously (10, 14). These phenomena are summarized in Fig. ​Fig.1.1. What is most striking is the fact that in addition to changing the ribosome's sensitivity to streptomycin, modification by RsmG seems to lower actinorhodin and SAM production through transcriptional effects. Somehow, the status of the ribosome is influencing the transcription of metK and actII-ORF4, the pathway-specific activator of the actinorhodin biosynthetic genes. FIG. 1. Summary of the known biochemical, transcriptional, translational, and resistance effects of the RsmG methyltransferase. In addition to addressing a 60-year-old question in antibiotic resistance, this work raises significant questions (12). It would appear that all bacteria, including the soil bacterium S. coelicolor, which may well share its habitat with streptomycin producers, encode a methyltransferase that makes them more sensitive to streptomycin. What do they gain from this? Loss of RsmG-mediated modification of the ribosome increases SAM synthetase production, translation efficiency during stationary phase, and remarkably, the production of the polyketide actinorhodin. How do the pathway-specific and pleiotropic antibiotic regulators identified in S. coelicolor contribute to this regulation? What is the significance of this chemical genetic interaction between the two types of streptomycin resistance and actinorhodin production, and does this sort of interaction extend to other antibiotics? This work is clearly an important step toward addressing these questions.

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  • Research Article
  • Cite Count Icon 3
  • 10.1186/s12879-021-06087-7
Antibiotic resistance among the Lahu hill tribe people, northern Thailand: a cross-sectional study
  • Apr 26, 2021
  • BMC Infectious Diseases
  • Sophaphan Intahphuak + 2 more

BackgroundAntibiotic resistance is often reported and great concerned as one of public health problems especially people living with poverty in developing countries including Thailand. The hill tribe people is defined as vulnerable population for antibiotic resistance in Thailand due to poor economic and education status particularly the Lahu people who is the second greatest group of the hill tribe people in Thailand. The study aimed to estimate the prevalence, factors associated with, and typing major species of bacteria with antibiotic drugs resistance among the Lahu hill tribe people in northern Thailand.MethodsA cross-sectional study was conducted to gather the information from the participants. A validated questionnaire was used for data collection. Participants who presented an illness related to infectious diseases were eligible to participate the study and were asked to obtain specific specimen; sputum, urine or stool. Antibiotic susceptibility was tested by Kirbey Bauer’s disc diffusion test. Chi-square and logistic regression were used to detect the associations between variables at the significant level of α = 0.05.ResultsA total of 240 participants were recruited into the study. The majority had urinary tract infection (67.9%) with two major pathogenic species of the infection; Escherichia coli (12.8%), and Enterobacter cloacae (8.0%). The prevalence of antibiotic resistance was 16.0%. Escherichia coli and Klebsiella pneumoniae species were found to have multidrug resistance that was greater than that of other species, while ampicillin was found to have the greatest drug resistance. It was found that those who had poor knowledge of antibiotic use had a 2.56-fold greater chance (95% CI = 1.09–5.32) of having antibiotic resistance than did those who had good knowledge of antibiotic use, and those who had poor antibiotic use behaviors had a 1.79-fold greater chance (95% CI = 1.06–4.80) of having antibiotic resistance than did those who had good antibiotic use behaviors.ConclusionEffective public health interventions are urgently needed to reduce antibiotic drug resistance among the Lahu people by improving their knowledge and skills regarding the proper use of antibiotics and eventually minimizing antibiotic resistance. Moreover, health care professionals should strictly follow the standard guideline to prescribe antibiotics.

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  • Supplementary Content
  • Cite Count Icon 42
  • 10.3390/molecules28072912
Efflux Pump Inhibitors in Controlling Antibiotic Resistance: Outlook under a Heavy Metal Contamination Context
  • Mar 24, 2023
  • Molecules
  • Thi Huyen Thu Nguyen + 10 more

Multi-drug resistance to antibiotics represents a growing challenge in treating infectious diseases. Outside the hospital, bacteria with the multi-drug resistance (MDR) phenotype have an increased prevalence in anthropized environments, thus implying that chemical stresses, such as metals, hydrocarbons, organic compounds, etc., are the source of such resistance. There is a developing hypothesis regarding the role of metal contamination in terrestrial and aquatic environments as a selective agent in the proliferation of antibiotic resistance caused by the co-selection of antibiotic and metal resistance genes carried by transmissible plasmids and/or associated with transposons. Efflux pumps are also known to be involved in either antibiotic or metal resistance. In order to deal with these situations, microorganisms use an effective strategy that includes a range of expressions based on biochemical and genetic mechanisms. The data from numerous studies suggest that heavy metal contamination could affect the dissemination of antibiotic-resistant genes. Environmental pollution caused by anthropogenic activities could lead to mutagenesis based on the synergy between antibiotic efficacy and the acquired resistance mechanism under stressors. Moreover, the acquired resistance includes plasmid-encoded specific efflux pumps. Soil microbiomes have been reported as reservoirs of resistance genes that are available for exchange with pathogenic bacteria. Importantly, metal-contaminated soil is a selective agent that proliferates antibiotic resistance through efflux pumps. Thus, the use of multi-drug efflux pump inhibitors (EPIs) originating from natural plants or synthetic compounds is a promising approach for restoring the efficacy of existing antibiotics, even though they face a lot of challenges.

  • Research Article
  • Cite Count Icon 3
  • 10.1186/s12879-025-10971-x
Prevalence, identification of virulence genes, and antibiotic resistance properties of Shiga-toxin producing Escherichia coli (STEC) strains isolated from ice cream and juice in sales centers
  • Apr 22, 2025
  • BMC Infectious Diseases
  • Elyas Shahrivar + 2 more

ObjectiveContaminated food with Shiga-toxin producing Escherichia coli (STEC) can cause diarrhea and severe diseases in consumers. This study aimed to assess the phenotypic and genotypic characteristics of virulence and antibiotic resistance genes in STEC strains isolated from various types of ice cream and fruit juice sold in Isfahan, Iran.MethodsFrom March 2023 to March 2024, 500 samples—including traditional ice cream (100), industrial ice cream (100), frozen ice cream (100), traditional juice (100), and industrial juice (100)—were collected. Samples were analyzed using biochemical and molecular methods for STEC detection. Antibiotic sensitivity was evaluated using the disc diffusion method against 14 antibiotics. Specific primers were used to identify antibiotic resistance and virulence genes.ResultsAmong the 500 samples, 52 (10.42%) were E. coli positive, with the highest prevalence found in traditional juice (20%) and traditional ice cream (15%). The pathogenic subtype, particularly enterohemorrhagic E. coli (EHEC), was most common in traditional juice (75% of positive samples) and traditional ice cream (66.66%). High antibiotic resistance rates were observed against ampicillin (86.53%), tetracycline (76.92%), and sulfamethoxazole (73.07%), while the lowest resistance was recorded for imipenem (7.69%). The most frequently detected antibiotic resistance genes were aadA1 (76.92%), tetA (57.69%), and sul1 (55.76%). Key virulence genes included stx1, stx2, and eaeA.ConclusionThese findings emphasize the public health risks associated with STEC contamination in food products and the need for stricter food safety measures and antibiotic stewardship programs. These findings highlight the public health risks of STEC contamination in food products, particularly traditional ice cream and juice. Localized studies are essential to understand specific risks and inform targeted interventions. Strategies such as improved hygiene practices, stringent food safety regulations, and effective antibiotic stewardship programs are critical to mitigating the threat posed by STEC in food products.

  • Research Article
  • Cite Count Icon 31
  • 10.2147/idr.s301318
Prevalence, Clinical Characteristics and Changes of Antibiotic Resistance in Children with Nontyphoidal Salmonella Infections from 2009–2018 in Chongqing, China
  • Apr 13, 2021
  • Infection and Drug Resistance
  • Li-Juan Wu + 3 more

PurposeNontyphoidal Salmonella (NTS) is a leading bacterial cause for acute gastroenteritis in children. With the increasing use of antibiotics worldwide, antibiotic resistance has become a global problem. However, data on NTS infections and changes in antibiotic resistance among children remain limited in China. We aimed to characterize the prevalence, clinical feature, serotype and the changes of antibiotic resistance of NTS in children in Chongqing.Methods501 hospitalized children with NTS infections (confirmed by positive NTS culture) in Children’s Hospital of Chongqing Medical University from January 2009 to December 2018 were included. The clinical data and drug sensitivity test results were retrospectively reviewed and analyzed. Antibiotic resistance in NTS infections was compared between 2009–2013 and 2014–2018.ResultsA total of 501 isolates were detected. Most NTS infections occurred in children under three years old, which mainly occurred between July and October. The numbers of patients with diarrhea, fever, and vomiting were 472 (94.2%), 422 (84.2%) and 146 (29.1%), respectively. Serogroup B (67.5%) was the predominant serogroup isolates. And Salmonella Typhimurium was the most common serotype (79.2%). The study compared the drug resistance of NTS from 2009 to 2013 with that from 2014 to 2018. We found the drug resistance rates of NTS to cefazolin, cefotaxime, ciprofloxacin, levofloxacin and imipenem showed an upward trend. The drug resistance rates of NTS to chloramphenicol, ampicillin, ceftriaxone, cefepime and compound sulfamethoxazole decreased slightly, but still showed high drug resistance rates. And drug resistance rates of NTS to piperacillin/tazobactam and ceftazidime decreased significantly in the last ten years. Multi-drug resistance (MDR) isolates, were detected among 69 cases (13.7%) of 501 children with NTS infections.ConclusionThe overall antibiotic resistance rates remained at a high level in Chongqing. Continuous surveillance of antibiotic resistance in NTS and control measures such as avoiding unnecessary antibiotic therapy in general NTS gastroenteritis are important. For severe or invasive infections caused by NTS infection in Southwest China, the use of ceftazidime is recommended until antibiotic sensitivity test results are available. And the choice of antibiotics should be based on the curative effect and the antibiotics sensitivity results.

  • Research Article
  • 10.31210/spi2025.28.04.19
Antibacterial activity of ethanolic clove Syzygium aromaticum extract against multidrug-resistant gram-negative bacteria
  • Dec 26, 2025
  • Scientific Progress &amp; Innovations
  • Amaal M Khudaier

The development of multidrug-resistant (MDR) bacteria is a significant global health concern, making the search for novel antimicrobial drugs crucial. Eugenol, a phenolic compound found in high concentration in Syzygium aromaticum (clove), is well known for its broad-spectrum antibacterial properties. The study aimed to evaluate the antibacterial activity of ethanolic clove Syzygium aromaticum extract against multidrug-resistant Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae). Bacterial isolates (E. coli, K. pneumoniae, and P. aeruginosa) were obtained from animal with infectious diseases and subsequently confirmed by cultivation on several plates of solidified agar media and incubation at 37 °C for 24 hours. Clove powder was processed into ethanolic extracts using standard maceration and evaporation techniques. Four concentrations of antibacterial activity (50 %, 25 %, 12.5 %, and 6.25 %) were tested using the agar well diffusion method. The results showed a concentration-dependent inhibitory effect, with the highest inhibition zones observed at 50 % concentration: E. coli (25 mm), P. aeruginosa (24 mm), and K. pneumoniae (20 mm). No inhibitory activity was observed at the 6.25 % concentration. Among the three microorganisms studied, the E. coli test culture demonstrated the highest sensitivity to ethanolic clove extract at concentrations of 12.5, 25.0, and 50.0 %, with growth inhibition zones of 16.0, 21.0 and 25.0 mm, respectively. In contrast, K. pneumoniae demonstrated the smallest inhibition zone (20 mm) at the highest extract concentration (50 %). Furthermore, research indicates that the combined use of clove extract with conventional antibiotics may result in a synergistic antibacterial effect. In conclusion, clove extract shows encouraging antibacterial activity against MDR Gram-negative bacteria and warrants futher research for potential medical application.

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