RESUMO
Plastid retrograde signaling plays a key role in coordinating the expression of plastid genes and photosynthesis-associated nuclear genes (PhANGs). Although plastid retrograde signaling can be substantially compromised by mitochondrial dysfunction, it is not yet clear whether specific mitochondrial factors are required to regulate plastid retrograde signaling. Here, we show that mitochondrial ATP synthase beta-subunit mutants with decreased ATP synthase activity are impaired in plastid retrograde signaling in Arabidopsis thaliana. Transcriptome analysis revealed that the expression levels of PhANGs were significantly higher in the mutants affected in the AT5G08670 gene encoding the mitochondrial ATP synthase beta-subunit, compared to wild-type (WT) seedlings when treated with lincomycin (LIN) or norflurazon (NF). Further studies indicated that the expression of nuclear genes involved in chloroplast and mitochondrial retrograde signaling was affected in the AT5G08670 mutant seedlings treated with LIN. These changes might be linked to the modulation of some transcription factors (TFs), such as LHY (Late Elongated Hypocotyl), PIF (Phytochrome-Interacting Factors), MYB, WRKY, and AP2/ERF (Ethylene Responsive Factors). These findings suggest that the activity of mitochondrial ATP synthase significantly influences plastid retrograde signaling.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , ATPases Mitocondriais Próton-Translocadoras , Plastídeos , Transdução de Sinais , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , Plastídeos/metabolismo , Plastídeos/genética , Mitocôndrias/metabolismo , Plântula/genética , Plântula/metabolismo , Mutação , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Lincomicina/farmacologia , Perfilação da Expressão GênicaRESUMO
The lincoamide antibiotic lincomycin, derived from Streptomyces lincolnensis, is widely used for the treatment of infections caused by gram-positive bacteria. As a common global regulatory factor of GntR family, DasR usually exists as a regulatory factor that negatively regulates antibiotic synthesis in Streptomyces. However, the regulatory effect of DasR on lincomycin biosynthesis in S. lincolnensis has not been thoroughly investigated. The present study demonstrates that DasR functions as a positive regulator of lincomycin biosynthesis in S. lincolnensis, and its overexpression strain OdasR exhibits a remarkable 7.97-fold increase in lincomycin production compared to the wild-type strain. The effects of DasR overexpression could be attenuated by the addition of GlcNAc in the medium in S. lincolnensis. Combined with transcriptome sequencing and RT-qPCR results, it was found that most structural genes in GlcNAc metabolism and central carbon metabolism were up-regulated, but the lincomycin biosynthetic gene cluster (lmb) were down-regulated after dasR knock-out. However, DasR binding were detected with the DasR responsive elements (dre) of genes involved in GlcNAc metabolism pathway through electrophoretic mobility shift assay, while they were not observed in the lmb. These findings will provide novel insights for the genetic manipulation of S. lincolnensis to enhance lincomycin production. KEY POINTS: ⢠DasR is a positive regulator that promotes lincomycin synthesis and does not affect spore production ⢠DasR promotes lincomycin production through indirect regulation ⢠DasR correlates with nutrient perception in S. lincolnensis.
Assuntos
Antibacterianos , Regulação Bacteriana da Expressão Gênica , Lincomicina , Streptomyces , Lincomicina/farmacologia , Lincomicina/biossíntese , Streptomyces/genética , Streptomyces/metabolismo , Streptomyces/efeitos dos fármacos , Antibacterianos/biossíntese , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Família Multigênica , Acetilglucosamina/metabolismo , Vias Biossintéticas/genética , Perfilação da Expressão GênicaRESUMO
Enhancing the efficiency of photosynthesis represents a promising strategy to improve crop yields, with keeping the steady state of PSII being key to determining the photosynthetic performance. However, the mechanisms whereby the stability of PSII is maintained in oxygenic organisms remain to be explored. Here, we report that the Psb28 protein functions in regulating the homeostasis of PSII under different light conditions in Arabidopsis thaliana. The psb28 mutant is much smaller than the wild-type plants under normal growth light, which is due to its significantly reduced PSII activity. Similar defects were seen under low light and became more pronounced under photoinhibitory light. Notably, the amounts of PSII core complexes and core subunits are specifically decreased in psb28, whereas the abundance of other representative components of photosynthetic complexes remains largely unaltered. Although the PSII activity of psb28 was severely reduced when subjected to high light, its recovery from photoinactivation was not affected. By contrast, the degradation of PSII core protein subunits is dramatically accelerated in the presence of lincomycin. These results indicate that psb28 is defective in the photoprotection of PSII, which is consistent with the observation that the overall NPQ is much lower in psb28 compared to the wild type. Moreover, the Psb28 protein is associated with PSII core complexes and interacts mainly with the CP47 subunit of PSII core. Taken together, these findings reveal an important role for Psb28 in the protection and stabilization of PSII core in response to changes in light environments.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Luz , Fotossíntese , Complexo de Proteína do Fotossistema II , Arabidopsis/metabolismo , Arabidopsis/genética , Complexo de Proteína do Fotossistema II/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Lincomicina/farmacologia , MutaçãoRESUMO
Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.
Assuntos
Antibacterianos , Flavonoides , Microbioma Gastrointestinal , Lincomicina , Sistema de Sinalização das MAP Quinases , Animais , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Suínos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Lincomicina/farmacologia , Camundongos , Disbiose/induzido quimicamente , Disbiose/tratamento farmacológico , Masculino , Intestinos/efeitos dos fármacos , Intestinos/patologiaRESUMO
Chloroplast function is essential for growth, development, and plant adaptation to stress. Organelle stress and plant defence responses were examined here using noxy8 (nonresponding to oxylipins 8) from a series of Arabidopsis mutants. The noxy8 mutation was located at the CLPC2 gene, encoding a chloroplast chaperone of the protease complex CLP. Although its CLPC1 paralogue is considered to generate redundancy, our data reveal significant differences distinguishing CLPC2 and CLPC1 functions. As such, clpc1 mutants displayed a major defect in housekeeping chloroplast proteostasis, leading to a pronounced reduction in growth and pigment levels, enhanced accumulation of chloroplast and cytosol chaperones, and resistance to fosmidomycin. Conversely, clpc2 mutants showed severe susceptibility to lincomycin inhibition of chloroplast translation and resistance to Antimycin A inhibition of mitochondrial respiration. In the response to Pseudomonas syringae pv. tomato, clpc2 but not clpc1 mutants were resistant to bacterial infection, showing higher salicylic acid levels, defence gene expression and 9-LOX pathway activation. Our findings suggest CLPC2 and CLPC1 functional specificity, with a preferential involvement of CLPC1 in housekeeping processes and of CLPC2 in stress responses.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Cloroplastos , Mutação , Estresse Fisiológico , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Cloroplastos/metabolismo , Regulação da Expressão Gênica de Plantas , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética , Pseudomonas syringae/fisiologia , Lincomicina/farmacologia , Doenças das Plantas/microbiologia , Ácido Salicílico/metabolismo , Proteínas de Cloroplastos/metabolismo , Proteínas de Cloroplastos/genéticaRESUMO
This study aims to indicate the influence of biochar on extracellular and intracellular ARGs (e/iARGs) variation and proliferation during lincomycin fermentation dregs (LFDs) compost. Biochar addition made iARGs keep reducing but eARGs increase to the maximum at the middle thermophilic phase and reduce at the end of the compost. Compared to control 3.15-log and 5.42-log reduction of iARGs and eARGs were observed, respectively. Biochar addition, bacterial community, and MGEs were the major contributors to iARGs and eARGs removal, with the contribution percentages of 38.4%, 31.0%, 23.7%, and 27.2%, 29.1%, and 34.9%, respectively. Moreover, biochar significantly inhibited eARGs transformation and RP4 plasmid conjugative transfer among E. coli DH5α and Pseudomonas aeruginosa HLS-6. The underlying mechanism involved in broken cell membranes of bacteria, and altered expression of oxidative stress genes and save our souls (SOS) response-related genes. The results indicated that biochar addition in composting could limit the dissemination of ARGs.
Assuntos
Antibacterianos , Carvão Vegetal , Compostagem , Antibacterianos/farmacologia , Lincomicina/farmacologia , Fermentação , Escherichia coli/genética , Genes Bacterianos/genética , Resistência Microbiana a Medicamentos/genética , Bactérias/genéticaRESUMO
This study aims to develop a pharmaceutical formulation that combines the potent antibacterial effect of lincomycin and lauric acid against Cutibacterium acnes (C. acnes), a bacterium implicated in acne. The selection of lauric acid was based on an in silico study, which suggested that its interaction with specific protein targets of C. acnes may contribute to its synergistic antibacterial and anti-inflammatory effects. To achieve our aim, glycerosomes were fabricated with the incorporation of lauric acid as a main constituent of glycerosomes vesicular membrane along with cholesterol and phospholipon 90H, while lincomycin was entrapped within the aqueous cavities. Glycerol is expected to enhance the cutaneous absorption of the active moieties via hydrating the skin. Optimization of lincomycin-loaded glycerosomes (LM-GSs) was conducted using a mixed factorial experimental design. The optimized formulation; LM-GS4 composed of equal ratios of cholesterol:phospholipon90H:Lauric acid, demonstrated a size of 490 ± 17.5 nm, entrapment efficiency-values of 90 ± 1.4 % for lincomycin, and97 ± 0.2 % for lauric acid, and a surface charge of -30.2 ± 0.5mV. To facilitate its application on the skin, the optimized formulation was incorporated into a carbopol hydrogel. The formed hydrogel exhibited a pH value of 5.95 ± 0.03 characteristic of pH-balanced skincare and a shear-thinning non-Newtonian pseudoplastic flow. Skin deposition of lincomycin was assessed using an in-house developed and validated LC-MS/MS method employing gradient elution and electrospray ionization detection. Results revealed that LM-GS4 hydrogel exhibited a two-fold increase in skin deposition of lincomycin compared to lincomycin hydrogel, indicating improved skin penetration and sustained release. The synergistic healing effect of LM-GS4 was evidenced by a reduction in inflammation, bacterial load, and improved histopathological changes in an acne mouse model. In conclusion, the proposed formulation demonstrated promising potential as a topical treatment for acne. It effectively enhanced the cutaneous absorption of lincomycin, exhibited favorable physical properties, and synergistic antibacterial and healing effects. This study provides valuable insights for the development of an effective therapeutic approach for acne management.
Assuntos
Acne Vulgar , Lincomicina , Camundongos , Animais , Lincomicina/farmacologia , Lincomicina/metabolismo , Lincomicina/uso terapêutico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Pele/metabolismo , Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Hidrogéis/farmacologia , Colesterol/metabolismoRESUMO
BACKGROUND: Sodium butyrate (SB) is a short-chain fatty acid and a safe antibiotic alternative. During 35 days, this study compared the impact of coated SB (Butirex C4) and lincomycin (Lincomix) on broiler growth, gut health, and litter hygiene in 1200 one-day-old Ross-308 broiler chicks that were randomly assigned into 5-dietary groups with 5-replications each. Groups divided as follows: T1: Basal diet (control), T2: Basal diet with buffered SB (1 kg/ton starter feed, 0.5 kg/ton grower-finisher feeds), T3: Basal diet with 100 g/ton lincomycin, T4: Basal diet with buffered SB (0.5 kg/ton starter feed, 0.25 kg/ton grower-finisher feeds) + 50 g/ton lincomycin, and T5: Basal diet with buffered SB (1 kg/ton starter feed, 0.5 kg/ton grower-finisher feeds) + 50 g/ton lincomycin. Birds were housed in a semi-closed deep litter house, where feed and water were available ad libitum. Results were statistically analyzed using ANOVA and Tukey's post hoc tests. RESULTS: Combined dietary supplementation with SB and lincomycin (T4 and T5) significantly enhanced body weights, weight gains, feed conversion ratio, and profitability index. Also, carcasses in T4 and T5 exhibited the highest dressing, breast, thigh, and liver yields. T5 revealed the best blood biochemical indices, while T3 showed significantly elevated liver and kidney function indices. T4 and T5 exhibited the highest expression levels of IGF-1 and TLR4 genes, the greatest villi length of the intestinal mucosa, and the lowest levels of litter moisture and nitrogen. Clostridia perfringens type A alpha-toxin gene was confirmed in birds' caeca, with the lowest clostridial counts defined in T4. CONCLUSIONS: Replacing half the dose of lincomycin (50 g/ton) with 0.5 or 1 kg/ton coated SB as a dietary supplement mixture showed the most efficient privileges concerning birds' performance and health.
Assuntos
Galinhas , Receptor 4 Toll-Like , Animais , Ácido Butírico/metabolismo , Lincomicina/farmacologia , Fator de Crescimento Insulin-Like I/genética , Dieta/veterinária , Suplementos Nutricionais , Ração Animal/análiseRESUMO
Potassium ions enhance photosynthetic tolerance to salt stress. We hypothesized that potassium ions, by minimizing the trans-thylakoid proton diffusion potential difference, can alleviate over-reduction of the photosynthetic electron transport chain and maintain the functionality of the photosynthetic apparatus. This study investigated the effects of exogenous potassium on the transcription level and activity of proteins related to the photosynthetic electron-transport chain of tobacco seedlings under salt stress. Salt stress retarded the growth of seedlings and caused an outflow of potassium ions from the chloroplast. It also lowered qP (indicator of the oxidation state of QA , the primary quinone electron acceptor in Photosystem II (PSII) and YPSII (average photochemical yield of PSII in the light-adapted state) while increasing YNO+NF (nonregulatory energy dissipation in functional and nonfunctional PSII), accompanied by decreased expression of most light-harvesting, energy-transduction, and electron-transport genes. However, exogenous potassium prevented these effects due to NaCl. Interestingly, lincomycin (an inhibitor of the synthesis of chloroplast-encoded proteins in PSII) significantly diminished the alleviation effect of exogenous potassium on salt stress. We attribute the comprehensive NaCl-induced downregulation of transcription and photosynthetic activities to retrograde signaling induced by reactive oxygen species. There probably exist at least two types of retrograde signaling induced by reactive oxygen species, distinguished by their sensitivity to lincomycin. Exogenous potassium appears to exert its primary effect by ameliorating the trans-thylakoid proton diffusion potential difference via a potassium channel, thereby accelerating ATP synthesis and carbon assimilation, alleviating over-reduction of the photosynthetic electron transport chain, and maintaining the functionality of photosynthetic proteins.
Assuntos
Potássio , Prótons , Transporte de Elétrons , Espécies Reativas de Oxigênio , Cloreto de Sódio/farmacologia , Fotossíntese/fisiologia , Estresse Salino , Complexo de Proteína do Fotossistema II/metabolismo , Lincomicina/farmacologiaRESUMO
The widespread use of antibiotics has created an antibiotic resistance genes (ARGs)-enriched environment, which causes high risks on human and animal health. Although antibiotics can be partially adsorbed and degraded in wastewater treatment processes, striving for a complete understanding of the microbial adaptive mechanism to antibiotic stress remains urgent. Combined with metagenomics and metabolomics, this study revealed that anammox consortia could adapt to lincomycin by spontaneously changing the preference for metabolite utilization and establishing interactions with eukaryotes, such as Ascomycota and Basidiomycota. Specifically, quorum sensing (QS) based microbial regulation and the ARGs transfer mediated by clustered regularly interspaced short palindromic repeats (CRISPR) system and global regulatory genes were the principal adaptive strategies. Western blotting results validated that Cas9 and TrfA were mainly responsible for the alteration of ARGs transfer pathway. These findings highlight the potential adaptative mechanism of microbes to antibiotic stress and fill gaps in horizontal gene transfer pathways in the anammox process, further facilitating the ARGs control through molecular and synthetic biology techniques.
Assuntos
Sistemas CRISPR-Cas , Percepção de Quorum , Animais , Humanos , Lincomicina/farmacologia , Multiômica , Oxidação Anaeróbia da Amônia , Antibacterianos/farmacologiaRESUMO
AtrA belongs to the TetR family and has been well characterized for its roles in antibiotic biosynthesis regulation. Here, we identified an AtrA homolog (AtrA-lin) in Streptomyces lincolnensis. Disruption of atrA-lin resulted in reduced lincomycin production, whereas the complement restored the lincomycin production level to that of the wild-type. In addition, atrA-lin disruption did not affect cell growth and morphological differentiation. Furthermore, atrA-lin disruption hindered the transcription of regulatory gene lmbU, structural genes lmbA and lmbW inside the lincomycin biosynthesis gene cluster, and 2 other regulatory genes, adpA and bldA. Completement of atrA-lin restored the transcription of these genes to varying degrees. Notably, we found that AtrA-lin directly binds to the promoter region of lmbU. Collectively, AtrA-lin positively modulated lincomycin production via both pathway-specific and global regulators. This study offers further insights into the functional diversity of AtrA homologs and the mechanism of lincomycin biosynthesis regulation.
Assuntos
Lincomicina , Streptomyces , Lincomicina/farmacologia , Lincomicina/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Regulação Bacteriana da Expressão Gênica , Antibacterianos/metabolismoRESUMO
Lincomycin is widely used in respiratory and gastrointestinal infection in veterinary medicine and food animal production. Campylobacter members are vital foodborne pathogens causing campylobacteriosis, and the resistance to lincosamides is seldom reported. To date, only the rRNA methyltransferase Erm(B) has been confirmed to be associated with lincosamides resistance in Campylobacter. In this study, we identified a lnu(C) variant conferring lincomycin resistance in this pathogen of chicken origin. The Lnu(C) encoded by this gene variant showed substitution at position 8 (Asn8Lys), 11 (Phe11Leu) and 112 (Leu112Phe), when compared with the firstly reported Lnu(C) from Streptococcus agalactiae. Cloning of the lnu(C) variant into lincosamide-susceptible Campylobacter jejuni NCTC 11168 confirmed its function in conferring resistance to lincomycin with the 32-fold increased MICs. Sequencing analysis showed that the lnu(C) variant was located within a MTnSag1-like transposon together with insLNU, which is inserted between panB and cj0299 genes on the chromosome. lnu(C) gene was distributed among C. coli globally, and various STs were involved in the dissemination of lnu(C). Although transposition mediated by MTnSag1-like transposon failed to occur, the horizontal transfer mediated by natural transformation and reservoir for resistance genes may facilitate their adaptation to the antimicrobial selection pressure in chickens, which should not be ignored.
Assuntos
Infecções por Campylobacter , Campylobacter coli , Campylobacter jejuni , Campylobacter , Animais , Lincomicina/farmacologia , Antibacterianos/farmacologia , Galinhas , Campylobacter coli/genética , Farmacorresistência Bacteriana/genética , Lincosamidas/farmacologia , Campylobacter jejuni/genética , Testes de Sensibilidade MicrobianaRESUMO
Streptomyces albus J1074 is one of the most popular heterologous expression platforms among streptomycetes. Identification of new genes and mutations that influence specialized metabolism in this species is therefore of great applied interest. Here, we describe S. albus KO-1304 that was isolated as a spontaneous lincomycin-resistant variant of double rpsLR94G rsmGR15SG40E mutant KO-1295. Besides altered antibiotic resistance profile, KO-1304 exhibited increased antibiotic activity as compared to its parental strains. KO-1304 genome sequencing revealed mutations within gene XNR_2147 encoding putative TetR-like protein. Gene XNR_2146 for efflux protein is the most likely target of repressing action of Xnr_2147. Our data agree with the scenario where lincomycin resistance phenotype of KO-1304 arose from inability of mutated Xnr_2147 protein to repress XNR_2146. Introduction of additional copy of XNR_2146 into wild type strain increased antibiotic activity of the latter, attesting to the practical value of transporter genes for strain improvement.
Assuntos
Lincomicina , Família Multigênica , Lincomicina/farmacologia , Mutação , Antibacterianos/farmacologiaRESUMO
Neat stallion semen can contain a variety of microorganisms, some of which may impair sperm quality and/or cause infection of the mares' reproductive tract. For this reason, antibiotics are commonly added to semen extenders. A combination of gentamicin, tylosin, lincomycin and spectinomycin (GTLS) has been recommended for use, but there are no reports on the use of this mixture in equine semen extender. Penicillin and amikacin (PA) are safe for preserving sperm quality while effectively controlling bacterial growth in equine cooled stored semen, but data on frozen semen are scarce. Therefore, a bioequivalence study was performed to assess the bactericidal activity of GTLS and PA in equine frozen semen. Nine mature, healthy stallions were used in the study. Split ejaculates were processed using media without antibiotics (Control) or with different antibiotics. For the GTLS group, centrifugation medium and freezing extender were prepared with gentamicin 250 µg/ml, tylosin 50 µg/ml, lincomycin 150 µg/ml and spectinomycin 300 µg/ml. For the PA group, the centrifugation medium was prepared with potassium penicillin G (PPG) 1200 units/ml and the freezing extender was prepared with PPG 1200 units/ml and amikacin 500 µg/ml. Semen processed in extenders without antibiotics had higher (p < .005) bacterial loads throughout all cryopreservation processing steps than semen samples processed using antibiotics. There were no differences in semen bacterial load after centrifugation, 15 and 30 min after final extension, and after thawing between GTLS and PA groups, but PA had faster (p < .05) kill-time kinetics than GTLS. Only minor differences in sperm kinetic parameters were observed among groups. In conclusion, this study demonstrated bioequivalence between GTLS and PA in mitigating end-point bacterial loads. Prudent concentrations of the antibiotic mixtures evaluated in this study can be considered both effective and sperm-safe for equine frozen semen.
Assuntos
Preservação do Sêmen , Espectinomicina , Animais , Cavalos , Masculino , Feminino , Espectinomicina/farmacologia , Lincomicina/farmacologia , Tilosina , Amicacina/farmacologia , Gentamicinas/farmacologia , Penicilinas , Preservação do Sêmen/veterinária , Sêmen/microbiologia , Antibacterianos/farmacologia , Espermatozoides/microbiologia , Criopreservação/veterinária , Motilidade dos EspermatozoidesRESUMO
The overuse of antibiotics has led to the emergence of resistant bacteria. A good alternative is silver nanoparticles, which have antibacterial activity against Gram-negative and Gram-positive bacteria, including multidrug-resistant strains. Their combination with already known antibiotics has a synergistic effect. In this work, we studied the synthesis of conjugates of silver nanoparticles with two antibiotics, lincomycin and cefazolin. Albumin and glutathione were used as spacer shells with functional groups. The physicochemical properties of the obtained conjugates, their cytotoxicity and synergism of antimicrobial activity were studied. The 50% antimicrobial activity of the obtained samples was shown, which allows them to be recommended for use as topical drug preparations.
Assuntos
Cefazolina , Nanopartículas Metálicas , Cefazolina/farmacologia , Lincomicina/farmacologia , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
OBJECTIVE: Salmonella isolates have been discovered in many regions of the world. We investigated the prevalence and resistance of Salmonella isolates in raw milk of healthy dairy cows on farms in different regions of Henan Province, China. MATERIALS AND METHODS: From July 2020 to November 2021, 422 raw milk samples were collected. The minimum inhibitory concentrations (MICs) of 16 antimicrobial agents against 89 Salmonella strains detected from the raw milk samples were determined using the broth microdilution method, and the resistance genes for fluoroquinolones were identified using polymerase chain reaction. RESULTS: Eighty-nine (21.09%) Salmonella isolates were recovered from 422 raw milk samples. The Salmonella strains exhibited high resistance to amoxicillin (100.00%), tylosin (95.50%), and lincomycin (95.50%). Additionally, tigecycline showed good activity against Salmonella, with an MIC50 of 0.25 µg/mL. All Salmonella isolates showed multidrug resistance (MDR), and >50% of the strains showed resistance to more than six antimicrobials. The strains from Jiaozuo exhibited 100% resistance to amoxicillin, terramycin, tylosin, and lincomycin. Two efflux pump genes, oqxA and oqxB, had the highest carrying rates of 66.29% and 64.04%, respectively. Additionally, the carrying rates of oqxA and oqxB were high in Shangqiu, Zhengzhou, and Jiaozuo. The carrying rates of aac(6')-Ib-cr in Shangqiu and Zhengzhou were 33.33% and 38.46%, respectively. CONCLUSIONS: This study revealed a high prevalence of Salmonella isolates obtained from raw milk of healthy dairy cows in different regions of Henan Province, China. The Salmonella strains exhibited various degrees of MDR. Salmonella can be transmitted to humans via consumption of contaminated raw milk; thus, the presence of resistance genes poses a potential threat to public health, highlighting the need for vigilant monitoring of Salmonella isolates.
Assuntos
Fluoroquinolonas , Oxitetraciclina , Amoxicilina , Animais , Antibacterianos/farmacologia , Bovinos , China/epidemiologia , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Lincomicina/farmacologia , Testes de Sensibilidade Microbiana , Leite , Fenótipo , Prevalência , Salmonella , Tigeciclina , TilosinaRESUMO
Staphylococcus equorum strain KM1031 is resistant to chloramphenicol, erythromycin and lincomycin. To shed light on the genetic factors underlying these antibiotic resistances, we determined the global gene expression profile of S. equorum KM1031 using RNA sequencing. During chloramphenicol, erythromycin and lincomycin treatment, 8.3% (183/2,336), 16.0% (354/2,336), and 2.9% (63/2,336) of S. equorum KM1031 genes exhibited significant differences in expression, respectively. These three antibiotics upregulated genes related to efflux and downregulated genes related to transporters. Antibiotic treatment also upregulated osmoprotectant-related genes involved in salt tolerance. To identify specific genes functionally related to antibiotic resistance, we compared the genome of strain KM1031 with those of three S. equorum strains that are sensitive to these three antibiotics. We identified three genes of particular interest: an antibiotic biosynthesis monooxygenase gene (abm, AWC34_RS01805) related to chloramphenicol resistance, an antibiotic ABC transporter ATP-binding protein gene (msr, AWC34_RS11115) related to erythromycin resistance, and a lincosamide nucleotydyltransferase gene (lnuA, AWC34_RS13300) related to lincomycin resistance. These genes were upregulated in response to the corresponding antibiotic; in particular, msr was upregulated more than fourfold by erythromycin treatment. Finally, the results of RNA sequencing were validated by quantitative real-time PCR. This transcriptomic analysis provides genetic evidence regarding antibiotic stress responses of S. equorum strain KM1031.
Assuntos
Alimentos Fermentados , Lincomicina , Transportadores de Cassetes de Ligação de ATP/genética , Trifosfato de Adenosina , Antibacterianos/farmacologia , Cloranfenicol/farmacologia , Eritromicina/farmacologia , Lincomicina/farmacologia , Oxigenases de Função Mista , Staphylococcus , TranscriptomaRESUMO
Mycoplasma hyorhinis is an emerging swine pathogen bacterium causing polyserositis and polyarthritis in weaners and finishers. The pathogen is distributed world-wide, generating significant economic losses. No commercially available vaccine is available in Europe. Therefore, besides improving the housing conditions for prevention, antimicrobial therapy of the diseased animals is the only option to control the infection. Our aim was to determine the minimal inhibitory concentrations (MIC) of ten antimicrobials potentially used against M. hyorhinis infection. The antibiotic susceptibility of 76 M. hyorhinis isolates from Belgium, Germany, Hungary, Italy and Poland collected between 2019 and 2021 was determined by broth micro-dilution method and mismatch amplification mutation assay (MAMA). Low concentrations of tiamulin (MIC90 0.312 µg/ml), doxycycline (MIC90 0.078 µg/ml), oxytetracycline (MIC90 0.25 µg/ml), florfenicol (MIC90 2 µg/ml) and moderate concentrations of enrofloxacin (MIC90 1.25 µg/ml) inhibited the growth of the isolates. For the tested macrolides and lincomycin, a bimodal MIC pattern was observed (MIC90 >64 µg/ml for lincomycin, tulathromycin, tylosin and tilmicosin and 5 µg/ml for tylvalosin). The results of the MAMA assay were in line with the conventional method with three exceptions. Based on our statistical analyses, significant differences in MIC values of tiamulin and doxycycline were observed between certain countries. Our results show various levels of antimicrobial susceptibility among M. hyorhinis isolates to the tested antibiotics. The data underline the importance of susceptibility monitoring on pan-European level and provides essential information for proper antibiotic choice in therapy.
Assuntos
Anti-Infecciosos , Infecções por Mycoplasma , Mycoplasma hyorhinis , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Doxiciclina/farmacologia , Europa (Continente) , Lincomicina/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/microbiologiaRESUMO
The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. It is, therefore, necessary to develop strategies for reducing the adverse effects of antibiotics. Studies on the harm and rescue measures of antibiotics from the perspective of the gut-liver system are lacking. Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. However, baicalin administration attenuated the lincomycin-induced changes. Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. Bile acids can regulate intestinal immunity and strengthen hepatoenteric circulation. In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. Thus, baicalin can ameliorate antibiotic-induced injury and its associated complications such as liver disease.
Assuntos
Inflamação , Lincomicina , Animais , Antibacterianos/efeitos adversos , Antibacterianos/metabolismo , Pré-Escolar , Flavonoides , Humanos , Inflamação/patologia , Lincomicina/metabolismo , Lincomicina/farmacologia , Lipídeos/farmacologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BLRESUMO
ABSTRACTMycoplasma iowae, a potential re-emerging avian pathogen mainly affecting turkeys, has been reported from many parts of the world. Poor hatchability, embryonic death, joint and skeletal abnormalities, poor ossification, runting-stunting, poor feathering and airsacculitis may be observed in infected flocks. The reduction of the severity of clinical signs and short-term control of M. iowae are performed by antibiotic treatment. However, M. iowae develops resistance more rapidly and is considered to be more resistant to antimicrobials than other avian pathogenic mycoplasmas. The aim of the present study was to determine the in vitro susceptibility of 101 M. iowae isolates and strains to ten clinically important antimicrobial agents, and to analyse and compare the susceptibility patterns of isolates of various origins and from a wide time-period. The examined reference strains showed high susceptibility to all antimicrobials except for spectinomycin. Low concentrations of tiamulin, florfenicol and oxytetracycline inhibited the growth of the clinical isolates. Nevertheless, slow tendency of increasing minimum inhibitory concentration (MIC) values was observed over time in the case of the above mentioned agents, while MIC values of enrofloxacin showed relatively rapid changes. Spiramycin, erythromycin, tilmicosin, tylosin, lincomycin and spectinomycin did not inhibit the bacterial growth in most of the cases. Isolates originating from captive game birds showed similar susceptibility profiles to isolates from industrial turkey hosts. The widely detected low susceptibility of M. iowae isolates to macrolides, lincomycin and spectinomycin, and the increase of MIC values of frequently used antimicrobials against this pathogen, emphasize the importance of targeted antibiotic therapy.RESEARCH HIGHLIGHTSAntimicrobial susceptibilities of 101 Mycoplasma iowae isolates were determined.Minimum inhibitory concentrations were determined by broth micro-dilution method.Tiamulin, oxytetracycline and florfenicol showed low MIC values.Isolates rapidly adapted to antimicrobial pressure.