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1.
Sci Total Environ ; 857(Pt 2): 159441, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36252660

RESUMO

Microorganisms are present as either biofilm or planktonic species in natural and engineered environments. Little is known about the selection pressure emanating from exposure to sub-minimal inhibitory concentration of antibiotics on planktonic vs. biofilm bacteria. In this study, an E. coli bioreporter was used to develop biofilms on glass and high-density polyethylene (HDPE) surfaces, and compared with the corresponding planktonic bacteria in antibiotic resistance expression when exposed to a range of µg/L levels of tetracycline. The antibiotic resistance-associated fluorescence emissions from biofilm E. coli reached up to 1.6 times more than those from planktonic bacteria. The intensively developed biofilms on glass surfaces caused the embedded bacteria to experience higher selection pressure and express more antibiotic resistance than those on HDPE surfaces. The temporal pattern of fluorescence emissions from biofilm E. coli was consistent with the biofilm-developing processes during the experimental period. The increased expression of antibiotic resistance from biofilm bacteria could be attributed to the high affinity of tetracycline with extracellular polymeric substances (EPS). The enhanced accumulation of tetracycline in biofilms could exert higher selection pressure on the embedded bacteria. These results suggest that in many natural and engineered systems the higher antibiotic resistance in biofilm bacteria could be attributed partially to the retention antibiotics by the EPS in biofilms.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Humanos , Polietileno , Tetraciclina/farmacologia , Biofilmes , Antibacterianos/farmacologia , Infecções por Escherichia coli/microbiologia , Resistência Microbiana a Medicamentos , Bactérias
2.
Braz J Microbiol ; 53(4): 2185-2194, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36279095

RESUMO

The aim of this study was to evaluate 140 Salmonella Derby isolates collected over a 10-year period from porcine origins (environment, pig carcass, lymph nodes, intestinal content, and pork) for their phenotypic and genotypic antimicrobial resistance, their ability to produce biofilm, and their genetic relatedness. The minimum inhibitory concentration (MIC) was determined using microdilution broth method and antimicrobial resistance genes were investigated by PCR. The quantification of biofilm formation was performed in sterile polystyrene microtiter plates. Genetic relatedness was determined by Xba-I macrorestriction analysis. The highest frequencies of non-wildtype (nWT) populations were observed against tetracycline (75.7%), streptomycin (70%), and colistin (11.4%), whereas wildtype populations were observed against ciprofloxacin, ceftazidime, and gentamicin. The resistance genes found were blaTEM (ampicillin), aadA variant (streptomycin/spectinomycin), tetA (tetracycline), and floR (florfenicol). On 96-well polystyrene microtiter plate, 68.6% of the isolates proved to be biofilm producers. Among 36 S. Derby isolates selected to PFGE analysis, 22 were clustered with 83.6% of similarity. Additionally, 27 isolates were clustered in 11 pulsotypes, which presented more than one strain with 100% of similarity. Most of S. Derby isolates were able to form biofilm and were classified as nWT or resistant to tetracycline, streptomycin, and colistin. PFGE allowed the identification of closely related S. Derby isolates that circulated in pig slaughterhouses and pork derived products along a decade.


Assuntos
Antibacterianos , Salmonella enterica , Suínos , Animais , Antibacterianos/farmacologia , Colistina/farmacologia , Poliestirenos , Farmacorresistência Bacteriana/genética , Carne/microbiologia , Salmonella , Testes de Sensibilidade Microbiana , Tetraciclina/farmacologia , Estreptomicina/farmacologia , Biofilmes , Farmacorresistência Bacteriana Múltipla/genética
3.
Genes (Basel) ; 13(10)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36292564

RESUMO

Tetracycline-inducible systems are widely used control elements for mammalian gene expression. Despite multiple iterations to improve inducibility, their use is still compromised by basal promoter activity in the absence of tetracyclines. In a mammalian system, we previously showed that the introduction of the G72V mutation in the rtTA-M2 tetracycline activator lowers the basal level expression and increases the fold-induction of multiple genetic elements in a long chimeric antigen receptor construct. In this study, we confirmed that the G72V mutation was effective in minimising background expression in the absence of an inducer, resulting in an increase in fold-expression. Loss of responsiveness due to the G72V mutation was compensated through the incorporation of four sensitivity enhancing (SE) mutations, without compromising promoter tightness. However, SE mutations alone (without G72V) led to undesirable leakiness. Although cryptic splice site removal from rtTA did not alter the inducible control of the luciferase reporter gene in this simplified vector system, this is still recommended as a precaution in more complex multi-gene elements that contain rtTA. The optimized expression construct containing G72V and SE mutations currently provides the best improvement of fold-induction mediated by the rtTA-M2 activator in a mammalian system.


Assuntos
Receptores de Antígenos Quiméricos , Tetraciclina , Animais , Tetraciclina/farmacologia , Receptores de Antígenos Quiméricos/genética , Sítios de Splice de RNA , Transativadores/genética , Tetraciclinas/farmacologia , Antibacterianos/uso terapêutico , Mamíferos/genética
4.
Int J Biol Macromol ; 222(Pt B): 2670-2682, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36220402

RESUMO

Herein, we report a multifunctional hydrogel membrane with good mechanical properties, excellent antioxidant efficiency, and broad-spectrum antimicrobial activity. For this purpose, a series of chitosan-carboxymethyl cellulose-Pluronic P123 (CHT-CMC-P123) hydrogel membranes were prepared by blending various tetracycline hydrochloride (TCH) contents. The physicochemical and biological properties of CHT-CMC-P123 membranes were comprehensively investigated. With the increase of TCH content from 5 % to 20 %, hydrogel membranes presented a decreased water contact angle from 18.96° to 11.24°, and a decreased water vapor transmission rate from 171.8 to 156.1 g/m2 h. Besides, with the increase of TCH content (5-20 %), the tensile strength (0.31-0.11 MPa) and elongation at break (10.57-4.82 %) of hydrogel membranes decreased while their thickness increased (113.5-324.3 µm). The data show that the release of TCH reached equilibrium after 26 days, with a cumulative percentage of approximately 28 %-87 %. Moreover, the hydrogel membranes exhibited a high antioxidant capacity of ~92 % for DPPH radical. Importantly, the incorporation of TCH significantly (~2.3 fold) enhanced the antimicrobial activity of the hydrogel membranes against Gram-positive, and Gram-negative bacteria and yeast. Based on our findings, these hydrogel membranes with superior properties may serve as effective food packaging and wound healing materials.


Assuntos
Anti-Infecciosos , Quitosana , Tetraciclina/farmacologia , Tetraciclina/química , Quitosana/química , Carboximetilcelulose Sódica/química , Hidrogéis/química , Antioxidantes/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química
5.
Chemosphere ; 309(Pt 2): 136666, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36220431

RESUMO

With the development of medical drugs, the widely used tetracycline has brought many adverse effects on the ecosystem and human health. Tetracycline pollution of water environment is becoming more and more serious, and has become an emerging environmental problem. As single celled organisms, microalgae are not only model organisms for risk assessment of aquatic ecosystems, but also can efficiently purify sewage. Microalgae-mediated pollutant remediation has attracted more and more attention from researchers. In this paper, Chlamydomonas reinhardtii (C. reinhardtii) was used to remove tetracycline in aqueous solution, and the removal efficiency and mechanism of microalgae on tetracycline were studied. The results showed that the removal rates of tetracycline by active and inactivated microalgae at a density of 5 × 106 cells·mL-1 were 81.9% and 89.8%, respectively. C. reinhardtii removed tetracycline through biosorption and nonmetabolic processes. Microalgal cell supernatant and hydroxyl radicals could significantly promote the removal of tetracycline. The positively charged tetracycline was electrostatically adsorbed on the microalgae surface and extracellular polymeric substances. Microalgae biomass can promote the production of ROS and enhance the ability of microalgae to remove tetracycline.


Assuntos
Chlamydomonas reinhardtii , Poluentes Ambientais , Microalgas , Humanos , Ecossistema , Esgotos , Espécies Reativas de Oxigênio/metabolismo , Tetraciclina/farmacologia , Microalgas/metabolismo , Biomassa , Antibacterianos/farmacologia , Água/metabolismo , Poluentes Ambientais/metabolismo , Águas Residuárias
6.
J Vet Med Sci ; 84(11): 1502-1507, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36198611

RESUMO

Campylobacter and non-typhoidal Salmonella are the major causes of bacterial gastrointestinal infections in humans. Although antimicrobial therapy is typically not recommended in many cases of these infections, it may be life-saving in patients with severe symptoms. Since chicken eggs and meat derived from layers are destined for human consumption, we investigated the prevalence and antimicrobial resistance of these two bacterial genera in 82 layer flocks at chicken processing plants in Honshu, Japan. Campylobacter was isolated from 77 flocks (93.9%). Resistance to ampicillin, tetracycline, and ciprofloxacin was documented in 42.3 (30/71), 16.9 (12/71), and 14.1% (10/71) of Campylobacter jejuni, respectively. Multilocus-sequence typing identified ST4389 and ST5262 as the most frequent C. jejuni sequence types. In C. coli, resistance to ampicillin, tetracycline, and ciprofloxacin was found in 20.0 (7/35), 20.0 (7/35), and 25.7% (9/35), respectively. The most frequent sequence type in C. coli was ST8292. Erythromycin resistance was not observed among Campylobacter species. Salmonella was isolated from 14 flocks (17.1%). The two most frequent serovars were Salmonella Corvallis and S. Braenderup. Neither S. Enteritidis nor S. Infantis were isolated. Streptomycin resistance was observed in six isolates (26.1%), and all isolates were susceptible to cefotaxime and ciprofloxacin. Thus, chicken eggs and meat derived from layers are possible sources of these bacterial infections in humans. The antimicrobial susceptibility of these isolates was maintained, reflecting restrictions on the use of antimicrobial agents on layers.


Assuntos
Infecções por Campylobacter , Campylobacter jejuni , Campylobacter , Humanos , Animais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Prevalência , Japão/epidemiologia , Testes de Sensibilidade Microbiana/veterinária , Campylobacter jejuni/genética , Salmonella , Infecções por Campylobacter/epidemiologia , Infecções por Campylobacter/veterinária , Infecções por Campylobacter/microbiologia , Ciprofloxacina/farmacologia , Tetraciclina/farmacologia , Galinhas/microbiologia , Ampicilina
7.
Chin Med J (Engl) ; 135(14): 1707-1715, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-36193978

RESUMO

BACKGROUND: High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI-amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment. METHODS: This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance. RESULTS: A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (-9.19% in the ITT analysis, - 9.21% in the MITT analysis, and -9.73% in the PP analysis) was greater than the predefined non-inferiority margin of -10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P  < 0.001). Symptom improvement rates and patients' compliance were similar between the two groups. CONCLUSIONS: Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04678492.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Amoxicilina , Antibacterianos/efeitos adversos , Bismuto , Quimioterapia Combinada , Esomeprazol/efeitos adversos , Esomeprazol/uso terapêutico , Furazolidona/farmacologia , Furazolidona/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Humanos , Citrato de Potássio/farmacologia , Citrato de Potássio/uso terapêutico , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Tetraciclina/farmacologia , Tetraciclina/uso terapêutico , Resultado do Tratamento
8.
Appl Environ Microbiol ; 88(19): e0112122, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36094214

RESUMO

Bacteria in the effluent of wastewater treatment plants (WWTPs) can transfer antibiotic resistance genes (ARGs) to the bacteria in receiving water through conjugation; however, there is a lack of quantitative assessment of this phenomenon in continuous cultures. Our objective was to determine the effects of background nutrient levels in river water column and growth rates of bacteria on the conjugation frequency of ARGs from effluent bacteria to river bacteria, as well as on the resulting resistance level (i.e., MICs) of the river bacteria. Chemostats were employed to simulate the discharge points of WWTPs into rivers, where effluent bacteria (donor cells) meet river bacteria (recipient cells). Both donor and recipient cells were Escherichia coli cells, and the donor cells were constructed by filter mating with bacteria in the effluent of a local WWTP. Results showed that higher bacterial growth rate (0.45 h-1 versus 0.15 h-1) led to higher conjugation frequencies (10-4 versus 10-6 transconjugant per recipient). The nutrient level also significantly affected the conjugation frequency, albeit to a lesser extent than the growth rate. The MIC against tetracycline increased from 2 mg/L in the recipient to 64 to 128 mg/L in transconjugants. In comparison, the MIC only increased to as high as 8 mg/L in mutants. Whole-genome sequencing showed that the tet-containing plasmid in both the donor and the transconjugant cells also occur in other fecal bacterial genera. The quantitative information obtained from this study can inform hazard identification related to the proliferation of wastewater-associated ARGs in surface water. IMPORTANCE WWTPs have been regarded as an important hot spot of ARGs. The discharge point of WWTP effluent, where ARGs may be horizontally transferred from bacteria of treated wastewater to bacteria of receiving water, is an important interface between the human-dominated ecosystem and the natural environment. The use of batch cultures in previous studies cannot adequately simulate the nutrient conditions and growth rates in receiving water. In this study, chemostats were employed to simulate the continuous growth of bacteria in receiving water. Furthermore, the experimental setup allowed for separate investigations on the effects of nutrient levels (i.e., simulating background nutrients in river water) and bacterial growth rates on conjugation frequencies and resulting resistance levels. The study generates statistically sound ecological data that can be used to estimate the risk of wastewater-originated ARGs as part of the One Health framework.


Assuntos
Antibacterianos , Águas Residuárias , Antibacterianos/farmacologia , Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Ecossistema , Escherichia coli/genética , Genes Bacterianos , Humanos , Nutrientes , Tetraciclina/farmacologia , Águas Residuárias/microbiologia , Água
9.
Int J Mol Sci ; 23(18)2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36142466

RESUMO

Tetracycline (TC) antibiotics can be detected worldwide in the aquatic environment due to their extensive use and low utilization efficiency, and they may affect the physiological processes of non-target organisms. In this study, the acute and sub-acute toxicities of TC on the freshwater microalga Scenedesmus obliquus were investigated with an emphasis on algal photosynthesis and transcription alterations during an 8 d TC exposure. The results showed that the IC10, IC30 and IC50 values were 1.8, 4.1 and 6.9 mg/L, respectively. During sub-acute exposure, the microalgae of the IC10 treatment was able to recover comparable growth to that of the control by day 7, while significantly lower cell densities were observed in the IC30 and IC50 treatments at the end of the exposure. The photosynthetic efficiency Fv/FM of S. obliquus first decreased as the TC concentration increased and then returned to a level close to that of the control on day 8, accompanied by an increase in photosynthetic activities, including light harvesting, electron transport and energy dissipation. Transcriptomic analysis of the IC10 treatment (1.8 mg/L TC) revealed that 2157 differentially expressed genes were up-regulated and 1629 were down-regulated compared with the control. KEGG and GO enrichments demonstrated that 28 photosynthesis-related genes involving light-harvesting chlorophyll protein complex, photosystem I, photosystem II, photosynthetic electron transport and enzymes were up-regulated, which may be the factor responsible for the enhanced photosynthesis and recovery of the microalgae. Our work may be helpful not only for gaining a better understanding of the environmental risk of TC at concentrations close to the real levels in natural waters, but also for explaining photosynthesis and related gene transcription induced by antibiotics.


Assuntos
Clorofíceas , Microalgas , Scenedesmus , Antibacterianos/farmacologia , Clorofíceas/metabolismo , Clorofila/metabolismo , Complexos de Proteínas Captadores de Luz/metabolismo , Microalgas/metabolismo , Fotossíntese , Complexo de Proteína do Fotossistema I/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Tetraciclina/farmacologia
10.
Int J Mol Sci ; 23(18)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36142896

RESUMO

Bacterial infections and inflammation are two main factors for delayed wound healing. Coaxial electrospinning nanofibrous patches, by co-loading and sequential co-delivering of anti-bacterial and anti-inflammation agents, are promising wound dressing for accelerating wound healing. Herein, curcumin (Cur) was loaded into the polycaprolactone (PCL) core, and broad-spectrum antibacterial tetracycline hydrochloride (TH) was loaded into gelatin (GEL) shell to prepare PCL-Cur/GEL-TH core-shell nanofiber membranes. The fibers showed a clear co-axial structure and good water absorption capacity, hydrophilicity and mechanical properties. In vitro drug release results showed sequential release of Cur and TH, in which the coaxial mat showed good antioxidant activity by DPPH test and excellent antibacterial activity was demonstrated by a disk diffusion method. The coaxial mats showed superior biocompatibility toward human immortalized keratinocytes. This study indicates a coaxial nanofiber membrane combining anti-bacterial and anti-inflammation agents has great potential as a wound dressing for promoting wound repair.


Assuntos
Curcumina , Nanofibras , Antibacterianos/química , Antioxidantes/farmacologia , Curcumina/farmacologia , Gelatina , Humanos , Nanofibras/química , Poliésteres/química , Tetraciclina/farmacologia , Água/química , Cicatrização
11.
Medicina (Kaunas) ; 58(9)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36143966

RESUMO

Background and Objectives: In spite of the fact that antibiotics are considered to be the cornerstone of modern medicine, their use in the treatment of cancer remains controversial. In the present study, the main objective was to examine the effects of two antibiotics-tetracycline and ampicillin-on the viability, morphology, migration, and organization and structure of the nuclei and the actin fiber network of pharyngeal carcinoma cells-Detroit-562. Materials and Methods: In order to determine the viability of the cells, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was applied after the cells were stimulated with five concentrations of tetracycline and ampicillin (10, 25, 50, 75, and 100 µM) for 72 h. A scratch assay was used to assess the migration ability of the cells. For the visualization of the nuclei and actin fibers, 4,6-diamidino-2-phenylindole (Dapi) and Rhodamine-Phalloidin were used. Results: There are different effects of tetracycline and ampicillin. Thus, tetracycline: (i) exhibited a concentration-dependent cytotoxic effect, decreasing cell viability to approximately 46%; (ii) inhibits cellular migration up to 16% compared to 60% for control cells; and (iii) induces changes in cell morphology as well as apoptotic changes in the nucleus and F-actin fibers. In contrast, in the case of ampicillin, an increase in viability up to 113% was observed at 10 µM, while a decrease in viability up to approximately 94% was observed at the highest concentration tested (100 µM). Conclusions: The results indicated a different effect regarding the impact on pharyngeal carcinoma cells. Thus, tetracycline has a concentration-dependent cytotoxic effect, while in the case of ampicillin a slight stimulation of cell viability was observed.


Assuntos
Antineoplásicos , Carcinoma , Actinas , Ampicilina/farmacologia , Ampicilina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Tetraciclina/farmacologia
12.
Curr Microbiol ; 79(10): 318, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088413

RESUMO

Lactobacilli are the most common probiotic bacteria found in the human gut microbiota, and the presence of acquired antibiotic resistance determinants carried on mobile genetic elements must be screened due to safety concerns. Unnecessary and inappropriate antibiotic therapy, as well as ingested antibiotic resistance bacteria (originating from food or food products), influence the abundance of antibiotic resistance genes in human guts, with serious clinical consequences. The current study looked into the antibiotic resistance of lactobacilli isolated from the guts of sepsis patients on long-term antibiotic therapy. The broth microdilution method was used to investigate the minimum inhibitory concentrations (MICs) of antibiotics such as imipenem, meropenem, erythromycin, tetracycline, cefepime, ciprofloxacin, and gentamycin, and the molecular genetic basis of resistance was studied based on the MIC values. The isolates were phenotypically resistant to tetracycline (20%), fluoroquinolone (20%), and macrolide (5%). Following that, resistance genes for tetracycline [tet(L), tet(O), tet(K), and tet(M)], macrolide [erm(B) and erm(C)], and beta-lactams [bla(CMY)] were investigated. Tetracycline or macrolide resistance genes were not found in the isolates, and only one isolate possessed the bla(CMY) resistance gene. The findings suggested that tetracycline and macrolide resistance may be linked to other resistance genes that were not investigated in this study. Because tetracyclines, fluoroquinolones, and macrolides are commonly used in clinics and animals, there has been concern about the spread of resistance in humans. If acquired antibiotic resistance is passed down through mobile genetic elements, it may serve as a reservoir of resistance for gut pathogens and other microbiome environments.


Assuntos
Antibacterianos , Sepse , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Farmacorresistência Bacteriana/genética , Humanos , Lactobacillus/genética , Macrolídeos/farmacologia , Prevalência , Sepse/tratamento farmacológico , Tetraciclina/farmacologia
13.
Front Cell Infect Microbiol ; 12: 970630, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159644

RESUMO

The increasing antibiotic resistance of Helicobacter pylori infection is a globally urging problem. To investigate the H. pylori resistance situation in Nanjing, China, we enrolled patients in Nanjing First Hospital from January 2018 to May 2021. H. pylori strains were isolated from patients who had at least one positive 13C-urea breath or rapid urease result. Subsequently, we performed antibiotic susceptibility tests on the isolated strains to clarithromycin, metronidazole, levofloxacin, amoxicillin, furazolidone and tetracycline. ARMS-PCR was conducted to determine H. pylori clarithromycin resistance gene mutation. Our results demonstrated that the primary resistance rates of metronidazole, clarithromycin, levofloxacin, amoxicillin, furazolidone and tetracycline were 67.19% (1417/2109), 35.99% (759/2109), 24.23% (511/2109), 0.76% (16/2109), 0.28% (6/2109) and 0.09% (2/2109), respectively. The resistance rates of metronidazole, clarithromycin and levofloxacin elevated significantly after treatment and the three antibiotics composed the majority of multi-resistance patterns. However, the resistance rates of amoxicillin, furazolidone and tetracycline were still in low levels after treatment. ARMS-PCR showed a rather good consistency with antibiotic susceptibility test in detecting clarithromycin resistance, with a kappa value of 0.79. Overall, this study revealed the latest complex situation of antibiotic resistance of H. pylori infection in Nanjing and offered suggestions on clinical medication for curing H. pylori.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana , Resistência Microbiana a Medicamentos , Furazolidona/farmacologia , Furazolidona/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana , Tetraciclina/farmacologia , Tetraciclina/uso terapêutico , Ureia/uso terapêutico , Urease
14.
ACS Appl Mater Interfaces ; 14(38): 43035-43049, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36124878

RESUMO

Antibacterial hydrogels have gradually become a powerful weapon to treat bacterially infected wounds and accelerate healing. In this paper, we designed a small-molecule self-healing antibacterial hydrogel containing 100% drug-loaded benzyl 3ß-amino-11-oxo-olean-12-en-30-oate (GN-Bn), which was governed by π-π stacking, hydrogen bonding, and van der Waals forces. Due to the carrier-free design concept, the problems of interbatch variability during sample preparation and carrier-related toxicity can be effectively avoided. Moreover, the GN-Bn hydrogel exhibited promising antibacterial activities against multidrug-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of the GN-Bn hydrogel was 1.5625 nmol/mL, which was lower than those against clinical agents such as norfloxacin, penicillin, and tetracycline. This is attributed to its unique antibacterial mechanism that aims at killing bacteria or preventing their growth by regulating arginine biosynthesis and metabolism through both transcriptomic (RNA-seq) analysis and quantitative polymerase chain reaction (qPCR) analysis. In addition, the GN-Bn hydrogel can also inhibit proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) to promote wound healing. Collectively, the GN-Bn hydrogel elicited dual therapeutic effects on an MRSA-infected full-thickness skin wound model through its antibacterial and anti-inflammatory activities, which is attributed to the fact that the GN-Bn hydrogel has multiple advantages including sufficient mechanical stability, biocompatibility, and unique antibacterial mechanisms, making it significantly accelerate MRSA-infected full-thickness skin wound healing as a wound dressing. In a word, the GN-Bn antibacterial hydrogel dressing with an anti-inflammatory and antibacterial bifunctional material holds great potential in clinical application.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Infecção dos Ferimentos , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Arginina/farmacologia , Bandagens , Humanos , Hidrogéis/farmacologia , Interleucina-6 , Norfloxacino , Penicilinas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Tetraciclina/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico
15.
Microbiol Spectr ; 10(5): e0161522, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36125305

RESUMO

The emergence of the plasmid-mediated high levels of the tigecycline resistance gene has drawn worldwide attention and has posed a major threat to public health. In this study, we investigated the prevalence of the tet(X4)-positive Enterobacterales isolates collected from a pig slaughterhouse and farms. A total of 101 tigecycline resistance strains were isolated from 353 samples via a medium with tigecycline, of which 33 carried tet(X4) (9.35%, 33/353) and 2 carried tet(X6) (0.57%, 2/353). These strains belong to seven different species, with Escherichia coli being the main host bacteria. Importantly, this report is the first one to demonstrate that tet(X4) was observed in Morganella morganii. Whole-genome sequencing results revealed that tet(X4)-positive bacteria can coexist with other resistance genes, such as blaNDM-1 and cfr. Additionally, we were the first to report that tet(X4) and blaNDM-1 coexist in a Klebsiella quasipneumoniae strain. The phylogenetic tree of 533 tet(X4)-positive E. coli strains was constructed using 509 strains from the NCBI genome assembly database and 24 strains from this study, which arose from 8 sources and belonged to 135 sequence types (STs) worldwide. We used Nanopore sequencing to interpret the selected 21 nonclonal and representative strains and observed that 19 tet(X4)-harboring plasmids were classified into 8 replicon types, and 2 tet(X6) genes were located on integrating conjugative elements. A total of 68.42% of plasmids carrying tet(X4) were transferred successfully with a conjugation frequency of 10-2 to 10-7. These findings highlight that diverse plasmids drive the widespread dissemination of the tigecycline resistance gene tet(X4) in Enterobacterales of porcine origin. IMPORTANCE Tigecycline is considered to be the last resort of defense against diseases caused by broad-spectrum resistant Gram-negative bacteria. In this study, we systematically analyzed the prevalence and genetic environments of the resistance gene tet(X4) in a pig slaughterhouse and farms and the evolutionary relationship of 533 tet(X4)-positive Escherichia coli strains, including 509 tet(X4)-positive E. coli strains selected from the 27,802 assembled genomes of E. coli from the NCBI between 2002 and 2022. The drug resistance of tigecycline is widely prevalent in pig farms where tetracycline is used as a veterinary drug. This prevalence suggests that pigs are a large reservoir of tet(X4) and that tet(X4) can spread horizontally through the food chain via mobile genetic elements. Furthermore, tetracycline resistance may drive tigecycline resistance through some mechanisms. Therefore, it is important to monitor tigecycline resistance, develop effective control measures, and focus on tetracycline use in the pig farms.


Assuntos
Escherichia coli , Drogas Veterinárias , Suínos , Animais , Tigeciclina/farmacologia , Filogenia , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Antibacterianos/farmacologia , Bactérias/genética , Tetraciclina/farmacologia , Inibidores da Síntese de Proteínas/farmacologia
16.
J Clin Invest ; 132(17)2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047498

RESUMO

Several classes of antibiotics have long been known for protective properties that cannot be explained through their direct antimicrobial effects. However, the molecular bases of these beneficial roles have been elusive. In this issue of the JCI, Mottis et al. report that tetracyclines induced disease tolerance against influenza virus infection, expanding their protection potential beyond resistance and disease tolerance against bacterial infections. The authors dissociated tetracycline's disease-resistance properties from its disease-tolerance properties by identifying potent tetracycline derivatives with minimal antimicrobial activity but increased capacity to induce an adaptive mitochondrial stress response that initiated disease tolerance mechanisms. These findings have potential clinical applications in viral infections.


Assuntos
Anti-Infecciosos , Infecções Bacterianas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Tetraciclina/farmacologia , Tetraciclinas/farmacologia , Tetraciclinas/uso terapêutico
17.
FEBS Open Bio ; 12(10): 1896-1908, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36062323

RESUMO

The tetracycline repressor (tetR)-regulated system is a widely used tool to specifically control gene expression in mammalian cells. Based on this system, we generated a human osteosarcoma cell line, which allows for the inducible expression of an EGFP fusion of the TAR DNA-binding protein 43 (TDP-43), which has been linked to neurodegenerative diseases. Consistent with previous findings, TDP-43 overexpression led to the accumulation of aggregates and limited the viability of U2OS. Using this inducible system, we conducted a chemical screen with a library that included FDA-approved drugs. While the primary screen identified several compounds that prevented TDP-43 toxicity, further experiments revealed that these chemicals abrogated the doxycycline-dependent TDP-43 expression. This antagonistic effect was observed with both doxycycline and tetracycline, and in several Tet-On cell lines expressing different genes, confirming the general effect of these compounds as inhibitors of the tetR system. Using the same cell line, a genome-wide CRISPR/Cas9 screen identified epigenetic regulators such as the G9a methyltransferase and TRIM28 as potential modifiers of TDP-43 toxicity. Yet again, further experiments revealed that G9a inhibition or TRIM28 loss prevented doxycycline-dependent expression of TDP-43. In summary, we have identified new chemical and genetic regulators of the tetR system, thereby raising awareness of the limitations of this approach to conduct chemical or genetic screening in mammalian cells.


Assuntos
Doxiciclina , Proteínas Repressoras , Antibacterianos , Proteínas de Ligação a DNA/genética , Doxiciclina/farmacologia , Expressão Gênica , Testes Genéticos , Humanos , Metiltransferases/genética , Proteínas Repressoras/metabolismo , Tetraciclina/farmacologia , Fatores de Transcrição/genética
18.
Biol Open ; 11(10)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36063129

RESUMO

The Gram-positive bacterium Staphylococcus aureus is responsible for a number of infections and has been described to exhibit resistance to antibacterial drugs through different resistance mechanisms. Among these, active efflux has been shown to be one of the main mechanisms of bacterial resistance associated with S. aureus. In this sense, the aim of the present study was to evaluate the ability of ellagic acid and gallic acid to reverse resistance by inhibiting the efflux pumps present in S. aureus strains IS-58 and K2068, which express the TetK and MepA flux pumps, respectively. In addition, the toxicity of both compounds was verified in Drosophila melanogaster. Broth microdilution assays were performed to obtain the minimum inhibitory concentration (MIC) values of ellagic acid and gallic acid, whereas efflux pump inhibition was tested using a subinhibitory concentration of standard efflux pump inhibitors, gallic acid and ellagic acid (MIC/8), where the ability of these compounds to decrease the MIC of ethidium bromide (EtBr) and antibiotics was verified. Toxicity was evaluated by mortality and negative geotaxis assays in D. melanogaster. Ellagic acid and gallic acid showed no direct antibacterial activity on S. aureus strains carrying the efflux pumps TetK and MepA. However, when we looked at the results for the TetK pump, we saw that when the two acids were associated with the antibiotic tetracycline, a potentiation of the antibacterial effect occurred; this behavior was also observed for the antibiotic ciprofloxacin in the MepA strain. For the efflux pump inhibition results, only the compound gallic acid showed potentiating effect on antibacterial activity when associated with the substrate EtBr for the IS-58 strain carrying the TetK efflux pump. Ellagic acid and gallic acid showed no toxicity on the model arthropod D. melanogaster. These results indicate the possible use of gallic acid as an adjuvant in antibiotic therapy against multidrug-resistant bacteria.


Assuntos
Ácido Elágico , Staphylococcus aureus , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/farmacologia , Ciprofloxacina/farmacologia , Drosophila melanogaster , Ácido Elágico/farmacologia , Etídio/farmacologia , Ácido Gálico/farmacologia , Tetraciclina/farmacologia
19.
Microbiol Spectr ; 10(5): e0166722, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36066254

RESUMO

Antibiotic tolerance not only enables bacteria to survive acute antibiotic exposures but also provides bacteria with a window of time in which to develop antibiotic resistance. The increasing prevalence of Campylobacter jejuni isolates resistant to clinically important antibiotics, particularly fluoroquinolones (FQs), is a global public health concern. Currently, little is known about antibiotic tolerance and its effects on resistance development in C. jejuni. Here, we show that exposure to ciprofloxacin or tetracycline at concentrations 10 and 100 times higher than the MIC induces antibiotic tolerance in C. jejuni, whereas gentamicin or erythromycin treatment causes cell death. Interestingly, FQ resistance rapidly develops in C. jejuni after tolerance induction by ciprofloxacin and tetracycline. Furthermore, after tolerance is induced, alkyl hydroperoxide reductase (AhpC) plays a critical role in reducing FQ resistance development by alleviating oxidative stress. Together, these results demonstrate that exposure of C. jejuni to antibiotics can induce antibiotic tolerance and that FQ-resistant (FQR) C. jejuni clones rapidly emerge after tolerance induction. This study elucidates the mechanisms underlying the high prevalence of FQR C. jejuni and provides insights into the effects of antibiotic tolerance on resistance development. IMPORTANCE Antibiotic tolerance compromises the efficacy of antibiotic treatment by extending bacterial survival and facilitating the development of mutations associated with antibiotic resistance. Despite growing public health concerns about antibiotic resistance in C. jejuni, antibiotic tolerance has not yet been investigated in this important zoonotic pathogen. Here, our results show that exposure of C. jejuni to ciprofloxacin or tetracycline leads to antibiotic tolerance development, which subsequently facilitates the emergence of FQR C. jejuni. Importantly, these antibiotics are commonly used in animal agriculture. Moreover, our study suggests that the use of non-FQ drugs in animal agriculture promotes FQ resistance development, which is crucial because antibiotic-resistant C. jejuni is primarily transmitted from animals to humans. Overall, these findings increase our understanding of the mechanisms of resistance development through the induction of antibiotic tolerance.


Assuntos
Campylobacter jejuni , Farmacorresistência Bacteriana , Fluoroquinolonas , Antibacterianos/farmacologia , Bactérias , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/genética , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana/genética , Eritromicina/farmacologia , Fluoroquinolonas/farmacologia , Gentamicinas/farmacologia , Testes de Sensibilidade Microbiana , Peroxirredoxinas/farmacologia , Tetraciclina/farmacologia
20.
Water Res ; 225: 119064, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36130438

RESUMO

Microbial electrolysis cell (MEC) is a promising technology for effective energy conversion of wastewater organics to biogas. Yet, in swine wastewater treatment, the complex contaminants including antibiotics may affect MEC performance, while the high ammonia concentration might increase this risk by increasing cell membrane permeability. In this work, the responses of MECs on tetracycline (TC) with low and high ammonia loadings (80 and 1000 mg L-1) were fully investigated. The TC of 0 to 1 mg L-1 slightly improved MEC performance in current production and electrochemical characteristics with low ammonia loading, while TC ≥ 4 mg L-1 started to show negative effects. Generally, the high ammonia loading sensitized MECs to TC concentration, inducing the current and COD removal of MECs to sharply decline with TC ≥ 0.5 mg L-1. The positive effect of high ammonia loading on MEC due to conductivity increase was counteracted with TC ≥ 1 mg L-1. The co-contamination of TC and ammonia significantly decreased the bioactivity and biomass of anode biofilm. Although the high concentration of co-existing TC and ammonia inhibited MEC performance, the reactors still obtained positive energy feedback. The network analyses indicated that the effluent suspension contributed much to antibiotic resistance gene (ARG) transmission, while the microplastics (MPs) in wastewater greatly raised the risks of ARGs spreading. This work systematically examined the synergetic effects of TC and ammonia and the transmission of ARGs in MEC operation, which is conducive to expediting the application of MECs in swine wastewater treatment.


Assuntos
Amônia , Águas Residuárias , Suínos , Animais , Biocombustíveis , Microplásticos , Plásticos , Eletrólise , Tetraciclina/farmacologia , Antibacterianos/farmacologia
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