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1.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915741

RESUMO

As an important zoonotic pathogen, Streptococcus suis (S. suis) can cause a variety of diseases both in human and animals, especially Streptococcal toxic shock-like syndrome (STSLS), which commonly appears in severe S. suis infection. STSLS is often accompanied by excessive production of inflammatory cytokines, which is the main cause of host death. Therefore, it is urgent to find a new strategy to relieve the damage caused by STSLS. In this study, we found, for the first time, that apigenin, as a flavonoid compound, could combine with ampicillin to treat severe S. suis infection. Studies found that apigenin did not affect the growth of S. suis and the secretion of suilysin (SLY), but it could significantly inhibit the hemolytic activity of SLY by directly binding to SLY and destroying its secondary structure. In cell assays, apigenin was found to have no significant toxic effects on effective concentrations, and have a good protective effect on S. suis-infected cells. More importantly, compared with the survival rate of S. suis-infected mice treated with only ampicillin, the survival rate of apigenin combined with an ampicillin-treated group significantly increased to 80%. In conclusion, all results indicate that apigenin in combination with conventional antibiotics can be a potential strategy for treating severe S. suis infection.


Assuntos
Ampicilina/farmacologia , Antibacterianos/farmacologia , Apigenina/farmacologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus suis/efeitos dos fármacos , Ampicilina/química , Ampicilina/uso terapêutico , Animais , Antibacterianos/química , Apigenina/química , Apigenina/uso terapêutico , Sítios de Ligação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Eritrócitos/efeitos dos fármacos , Proteínas Hemolisinas/antagonistas & inibidores , Proteínas Hemolisinas/química , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ligação Proteica , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/metabolismo , Relação Estrutura-Atividade , Resultado do Tratamento
2.
Appl Environ Microbiol ; 87(10)2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33712420

RESUMO

The emergence and spread of extended-spectrum ß-lactamases (ESBLs), metallo-ß-lactamases (MBLs), or variant low-affinity penicillin-binding proteins (PBPs) pose a major threat to our ability to treat bacterial infection using ß-lactam antibiotics. Although combinations of ß-lactamase inhibitors with ß-lactam agents have been clinically successful, there are no MBL inhibitors in current therapeutic use. Furthermore, recent clinical use of new-generation cephalosporins targeting PBP2a, an altered PBP, has led to the emergence of resistance to these antimicrobial agents. Previous work shows that natural polyphenols such as cranberry-extracted proanthocyanidins (cPAC) can potentiate non-ß-lactam antibiotics against Gram-negative bacteria. This study extends beyond previous work by investigating the in vitro effect of cPAC in overcoming ESBL-, MBL-, and PBP2a-mediated ß-lactam resistance. The results show that cPAC exhibit variable potentiation of different ß-lactams against ß-lactam-resistant Enterobacteriaceae clinical isolates as well as ESBL- and MBL-producing E. coli We also discovered that cPAC have broad-spectrum inhibitory properties in vitro on the activity of different classes of ß-lactamases, including CTX-M3 ESBL and IMP-1 MBL. Furthermore, we observe that cPAC selectively potentiate oxacillin and carbenicillin against methicillin-resistant but not methicillin-sensitive staphylococci, suggesting that cPAC also interfere with PBP2a-mediated resistance. This study motivates the need for future work to identify the most bioactive compounds in cPAC and to evaluate their antibiotic-potentiating efficacy in vivo IMPORTANCE The emergence of ß-lactam-resistant Enterobacteriaceae and staphylococci compromises the effectiveness of ß-lactam-based therapy. By acquisition of ESBLs, MBLs, or PBPs, it is highly likely that bacteria may become completely resistant to the most effective ß-lactam agents in the near future. In this study, we described a natural extract rich in proanthocyanidins which exerts adjuvant properties by interfering with two different resistance mechanisms. By their broad-spectrum inhibitory ability, cranberry-extracted proanthocyanidins could have the potential to enhance the effectiveness of existing ß-lactam agents.


Assuntos
Ampicilina/farmacologia , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Cefotaxima/farmacologia , Proantocianidinas/farmacologia , Vaccinium macrocarpon , Bactérias/crescimento & desenvolvimento , Sinergismo Farmacológico , Resistência beta-Lactâmica/efeitos dos fármacos
3.
Lett Appl Microbiol ; 72(5): 535-541, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33421175

RESUMO

Exudative epidermatitis or greasy pig disease (GPD) is a contagious disease of pig and endemic worldwide caused by toxigenic strains under genus Staphylococcus. The present study reported an outbreak of GPD in Champhai district of Mizoram adjoining to the southern border of Myanmar. A total of 60 samples were collected from 22 clinically affected animals and processed for isolation and identification of Staphylococcus spp. All the isolates were subjected to antimicrobial sensitivity assay, biofilm production assay and detection of virulence genes, biofilm genes and mec genes followed by cloning and sequencing for phylogenetic analysis. A total of 44 staphylococci belonged to four species (S. sciuri, S. aureus,S. lentus, and S. hyicus) were isolated. Majority of the isolates were multidrug resistant with maximum resistance against ampicillin, penicillin including vancomycin. None of the S. hyicus isolates was methicillin resistant (MRSH) but 66·67% isolates were MRSA. By PCR, mecA gene was detected in S. aureus (n = 2), S. sciuri (n = 4) and S. lentus (n = 3). Biofilm associated gene icaD was detected in S. aureus (n = 3), S. sciuri (n = 5), S. hyicus (n = 4) and S. lentus (n = 6). The exfoliative toxin genes (ehxB, shetA and tsst1) were detected in S. hyicus (n = 3) and S. aureus (n = 1) isolates. All the isolates were closely related with the isolates from pigs of China, Germany, Japan and USA. The pathogens might be transmitted through illegal migration of pigs from Myanmar to India.


Assuntos
Epidermite Exsudativa do Suíno/epidemiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/veterinária , Staphylococcus hyicus/isolamento & purificação , Staphylococcus/isolamento & purificação , Ampicilina/farmacologia , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Surtos de Doenças , Farmacorresistência Bacteriana Múltipla/genética , Epidermite Exsudativa do Suíno/microbiologia , Índia/epidemiologia , Resistência a Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas/genética , Penicilinas/farmacologia , Filogenia , Infecções Estafilocócicas/epidemiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/genética , Staphylococcus hyicus/efeitos dos fármacos , Staphylococcus hyicus/genética , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/microbiologia , Vancomicina/farmacologia , Virulência
4.
Int J Biol Macromol ; 172: 350-359, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33453258

RESUMO

The improper management of wound exudates can expose the wound to bacterial invasion, skin maceration etc. thereby resulting in prolonged wound healing. Biopolymers are characterized by hydrophilic functional groups which when employed for the development of wound dressings promote the wound dressings capability to absorb a high amount of wound exudates. Alginate-gum acacia sponges were prepared from a combination of biopolymers such as sodium alginate and gum acacia in varying amounts with carbopol via crosslinking with 1 and 2% CaCl2. The prepared sponges were loaded with a combination of ampicillin and norfloxacin. In vitro antibacterial analysis revealed that the antibacterial activity of the loaded antibiotics was retained and the sponges were effective against gram-positive and gram-negative bacteria. The sponges displayed rapid and high absorption capability in the range of 1022-2419% at pH 5.5 simulating wound exudates, and 2268-5042% at pH 7.4 simulating blood within a period of 1-3 h. Furthermore, the whole blood clotting studies further revealed low absorbance values when compared to the control revealing the good clotting capability of the sponges. The unique features of the sponges revealed their potential application for the management of infected, high exuding and bleeding wounds.


Assuntos
Resinas Acrílicas/química , Alginatos/química , Antibacterianos/farmacologia , Bandagens , Cloreto de Cálcio/química , Goma Arábica/química , Ampicilina/química , Ampicilina/farmacologia , Antibacterianos/química , Coagulação Sanguínea/efeitos dos fármacos , Liofilização/métodos , Humanos , Testes de Sensibilidade Microbiana , Norfloxacino/química , Norfloxacino/farmacologia , Porosidade , Proteus vulgaris/efeitos dos fármacos , Proteus vulgaris/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/crescimento & desenvolvimento
5.
Environ Sci Pollut Res Int ; 28(20): 25228-25240, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33453031

RESUMO

Ampicillin and tetracycline are common antibiotics and can threaten humans by inducing antibiotic resistance in bacteria. Microorganisms are usually exposed to a mixed antibiotic system in the environment. However, there are few researches on the specific regulatory mechanisms of clay on microorganisms under the stress of complex antibiotics. In this study, tandem mass tag-based coupled with two-dimensional liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) was employed to recognize and quantify changes in protein expression of Escherichia coli (E. coli) after culture for 15 days, with or without kaolinite in the co-stress of ampicillin and tetracycline. The results indicated that kaolinite could activate metabolic pathways of E. coli such as the energy metabolism, the biosynthesis of other secondary metabolites, and the metabolism of cofactors and vitamins. Particularly, the fatty acid degradation pathway has also been promoted, indicating that in the same unfavorable environment, kaolinite might influence the composition of E. coli cell membranes. This might be due to the change in membrane composition that was a kind of adaptive strategy of bacterial evolution. Moreover, kaolinite could promote multidrug efflux system to export the bacterial intracellular toxic substances, making E. coli survive better in an adverse environment. Consequently, this study not only disclosed the regulation of kaolinite on E. coli in a complex antibiotic environment but also provided new insights into the environmental process of antibiotic resistance.


Assuntos
Escherichia coli , Caulim , Ampicilina/farmacologia , Antibacterianos/farmacologia , Cromatografia Líquida , Humanos , Espectrometria de Massas em Tandem , Tetraciclina/farmacologia
6.
Anal Bioanal Chem ; 413(4): 1127-1136, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33420534

RESUMO

Antibiotic resistance has become a serious threat to food safety and public health globally. Therefore, the development of a sensitive, quick, and simple method for antibiotic susceptibility testing is an urgent and crucial need. A novel concentration gradient microfluidic chip was designed in this work to generate antibiotic concentration gradient, culture bacteria, and produce fluorescence emission. An in-house-assembled fluorescence detection platform was constructed, and experiments were conducted to verify the linearity of the generated concentration gradient, explore the appropriate incubation time and flow rate for the microfluidic chip, and study the effect of long-term acid-based food processing on antibiotic susceptibility testing. Experimental results show that the concentration gradient generated by the microfluidic chip exhibited good linearity, stability, and controllability. The appropriate flow rate and incubation time for the microfluidic chip were 2 µL/min and 5 h, respectively. The use of this microfluidic chip for testing antibiotic resistance of Salmonella to ofloxacin and ampicillin generated results that were completely consistent with test results obtained using the gold-standard method. Furthermore, Salmonella showed greater sensitivity to antibiotics under strong acid conditions, confirming the potential influence of acid-based food processing on antibiotic susceptibility testing of real samples. The designed microfluidic chip provides a high-throughput, sensitive, and rapid antibiotic susceptibility testing method that combines the microfluidic chip and the fluorescence detection platform. The application of this method would facilitate determination of antibiotic-resistant bacterial strains for clinicians and researchers, and enable monitoring of changes in bacterial resistance during food processing.


Assuntos
Antibacterianos/farmacologia , Ensaios de Triagem em Larga Escala/instrumentação , Testes de Sensibilidade Microbiana/instrumentação , Técnicas Analíticas Microfluídicas/instrumentação , Salmonella/efeitos dos fármacos , Ampicilina/farmacologia , Farmacorresistência Bacteriana , Desenho de Equipamento , Humanos , Ofloxacino/farmacologia , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia
7.
Int J Food Microbiol ; 334: 108819, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-32818765

RESUMO

In a viable but nonculturable (VBNC) state, bacteria are no longer culturable on standard laboratory media, but still, remain a pathogenic potential and present possible health risks. In this study, we investigated ampicillin's ability, which is commonly used in dairy cattle disease treatment, to induce Cronobacter sakazakii into the VBNC state. After treatment with ampicillin, the counts of culturable cells decreased from 108 CFU/mL to an undetected level 7-30 days post-treatment. Meanwhile, viable cells were still approximately 104-105 cells/mL, and could be resuscitated under appropriate conditions. Fluorescence microscopy showed that VBNC cell maintained apparent cellular integrity, but that the morphology of VBNC cells differed visibly from that of normal cells. Moreover, the respiratory chain activity of VBNC cells were confirmed by flow cytometry (FCM) analysis, suggesting that cells in a VBNC state were physiologically active. Finally, transcriptomics analysis and real-time PCR (qPCR) validation were used to explore the underlying mechanisms of VBNC cell formation. Over-expression of relA, lon, ppx, and ppk in the toxin-antitoxin (TA) trigger system contributed to VBNC cell formation. In the TA trigger system, RelA and exopolyphosphatases/guanosine pentaphosphate phosphohydrolases (PPX/GPPA) synthesize ppGpp, which activates polyphosphate kinase (PPK), the cellular enzyme that accumulates plyphosphate (PolyP). PolyP combines with and stimulates Lon to degrade the antitoxins, thereby activating the toxins that induce a VBNC state. The results of our research will facilitate a better understanding of the survival strategies that bacteria develop to deal with ampicillin pressure and the health risks associated with VBNC Cronobacter sakazakii induced by antibiotics.


Assuntos
Ampicilina/farmacologia , Antibacterianos/farmacologia , Cronobacter sakazakii/efeitos dos fármacos , Cronobacter sakazakii/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Contagem de Colônia Microbiana , Cronobacter sakazakii/genética , Cronobacter sakazakii/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Sistemas Toxina-Antitoxina/genética
8.
PLoS Pathog ; 16(7): e1008700, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32687537

RESUMO

With antibiotic resistance rates on the rise, it is critical to understand how microbial species interactions influence the evolution of resistance. In obligate mutualisms, the survival of any one species (regardless of its intrinsic resistance) is contingent on the resistance of its cross-feeding partners. This sets the community antibiotic sensitivity at that of the 'weakest link' species. In this study, we tested the hypothesis that weakest link dynamics in an obligate cross-feeding relationship would limit the extent and mechanisms of antibiotic resistance evolution. We experimentally evolved an obligate co-culture and monoculture controls along gradients of two different antibiotics. We measured the rate at which each treatment increased antibiotic resistance, and sequenced terminal populations to question whether mutations differed between mono- and co-cultures. In both rifampicin and ampicillin treatments, we observed that resistance evolved more slowly in obligate co-cultures of E. coli and S. enterica than in monocultures. While we observed similar mechanisms of resistance arising under rifampicin selection, under ampicillin selection different resistance mechanisms arose in co-cultures and monocultures. In particular, mutations in an essential cell division protein, ftsI, arose in S. enterica only in co-culture. A simple mathematical model demonstrated that reliance on a partner is sufficient to slow the rate of adaptation, and can change the distribution of adaptive mutations that are acquired. Our results demonstrate that cooperative metabolic interactions can be an important modulator of resistance evolution in microbial communities.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Resistência Microbiana a Medicamentos/fisiologia , Escherichia coli/fisiologia , Interações Microbianas/fisiologia , Salmonella enterica/fisiologia , Adaptação Fisiológica/genética , Ampicilina/farmacologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Técnicas de Cocultura , Escherichia coli/efeitos dos fármacos , Interações Microbianas/efeitos dos fármacos , Modelos Teóricos , Mutação , Rifampina/farmacologia , Salmonella enterica/efeitos dos fármacos
9.
Lett Appl Microbiol ; 71(4): 359-368, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32713031

RESUMO

Staphylococci from Sheedal of Northeast India was isolated, identified and characterized. All the isolated staphylococci were found to be coagulase negative. Based on the rpoB gene sequences followed by analysis using NCBI-BLAST software, seven species of Staphylococcus namely, S. piscifermentans, S. condimenti, S. arlettae, S. sciuri, S. warneri, S. nepalensis and S. hominis were recognized. Phylogenetic analyses revealed three major cluster groups. All the seven Staphylococcus showed their NaCl tolerance from 2 to 8%. No species was able to grow at 55°C. Except S. arlettae and S. sciuri, all the isolated staphylococcal species exhibited growth at pH 4-8. No isolated species was able to ferment mannitol, sucrose and arabinose. All the species exhibited moderate to maximum proteolytic and lipolytic activities. All the seven species were found to be sensitive to the antibiotics, namely, erythromycin, norfloxacin, ampicillin, streptomycin and vancomycin, whereas all were resistant to co-trimoxazole. Only S. piscifermentans was found antagonist to Salmonella enterica, Escherichia coli and Bacillus subtilis, although the clear zone was minimal. All the staphylococcal species except S. arlettae and S. sciuri exhibited hydrophobicity ranging from 25 to 66%. The observed characteristics of isolated Staphylococci from Sheedal revealed their role in fish fermentation.


Assuntos
Alimentos e Bebidas Fermentados/microbiologia , Produtos Pesqueiros/microbiologia , Staphylococcus/isolamento & purificação , Ampicilina/farmacologia , Animais , Antibacterianos/farmacologia , Eritromicina/farmacologia , Fermentação , Peixes/microbiologia , Contaminação de Alimentos/análise , Índia , Filogenia , Staphylococcus/classificação , Staphylococcus/efeitos dos fármacos , Staphylococcus/genética
10.
J Med Microbiol ; 69(7): 928-931, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32584214

RESUMO

Introduction. The therapeutic options to treat Acinetobacter baumannii infections are very limited.Aim. Our aim was to evaluate the activity of sulbactam combined directly with avibactam or the ampicillin-sulbactam/ceftazidime-avibactam combination against extensively drug-resistant A. baumannii isolates.Methodology. Extensively drug-resistant A. baumannii isolates (n=127) collected at several South American hospitals were studied. Synergy with the sulbactam/avibactam combination was assessed in all isolates using the agar dilution method. Avibactam was used at a fixed concentration of 4 mg l-1. A disc diffusion synergy test was also performed. Synergy by a time-kill experiment was performed in a selected isolate.Results. Synergy with sulbactam/avibactam was demonstrated in 124 isolates and it showed MIC values ≤4 mg l-1. This synergy was not detected in the three New Delhi metallo-ß-lactamase-harbouring isolates. Similar results were observed with the disc diffusion synergy test of ampicillin-sulbactam/ceftazidime-avibactam. In the time-kill experiments, sulbactam/avibactam showed a rapid synergistic and bactericidal activity in ampicillin-sulbactam-resistant isolates.Conclusions. This study demonstrated that the sulbactam/avibactam combination displayed synergistic activity against A. baumannii isolates. This synergy was observed when both inhibitors were also used as part of the commercially available combinations: ampicillin-sulbactam and ceftazidime-avibactam.


Assuntos
Infecções por Acinetobacter/terapia , Compostos Azabicíclicos/metabolismo , Sulbactam/farmacologia , Infecções por Acinetobacter/metabolismo , Acinetobacter baumannii/metabolismo , Ampicilina/farmacologia , Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Ceftazidima/farmacologia , Combinação de Medicamentos , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Quimioterapia Combinada/métodos , Humanos , Testes de Sensibilidade Microbiana , Tienamicinas/farmacologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-32539543

RESUMO

Wild animals like pheasant seem to be a good source of information about human activities. Therefore, the wild pheasants and relative stable appendix microcenosis were selected for antibiotic resistance testing. Penicillin resistance by MALDI-TOF Mass Spectrometry and tetracyclines resistance by genetic methods using specific primers were tested. Differences between tetracycline and penicillin resistance were detected. Results showed high prevalence of resistant Escherichia coli isolated from wild pheasant appendix. E. coli isolated from wild pheasant appendix carried plasmids for penicillins and tetracyclines resistance where they were responsible for enzymatic degradation of penicillin and carried genes for regulating efflux pumps for tetracyclines. Results showed that tetracyclines and penicillins resistance is widespread between wild pheasants with a carrier as Escherichia coli isolated from relative stable microcenosis of appendix.


Assuntos
Monitoramento Ambiental/métodos , Escherichia coli/genética , Galliformes/microbiologia , Resistência às Penicilinas/genética , Resistência a Tetraciclina/genética , Ampicilina/farmacologia , Animais , Animais Selvagens , Apêndice/microbiologia , Escherichia coli/efeitos dos fármacos , Humanos , Eslováquia , Tetraciclina/farmacologia
12.
J Appl Microbiol ; 129(5): 1238-1247, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32430970

RESUMO

AIMS: To analyse and compare the effect of selection power for antimicrobial resistance (AMR) in coliforms of two kinds of ß-lactams-aminopenicillins; ampicillin (Amp) and cephalosporins; cephalexin (Cpn) and ceftiofur (Cef)-and tetracycline (Tet) using an approach based on a swine faecal microcosmos. METHODS AND RESULTS: Sixteen faecal samples from 32 pigs (mixed two by two) were treated with Amp, Cpn, Cef and Tet for 6 h (T6h) at concentrations expected to reach the animals gut when using in vivo standard doses. Controls (no drug added) were also tested. Next, samples were 1 : 100 diluted and left under the same conditions (no antimicrobial added) for further 20 h (T20h). The proportion of resistant coliform bacteria (R coliforms) to each antimicrobial was analysed just before starting the treatment (T0), at T6h and at T20h. Coselection was also studied by replica plating. Treatment for 6 h yielded significant increase in proportion of R coliforms, regardless of the drug and lack of selection pressure showed different effects at T20h depending on the antimicrobial used. Selective pressure was associated with the type of the ß-lactam with Amp selecting for significantly higher numbers of R coliforms than cephalosporins. CONCLUSIONS: AMR development was observed following short treatment, and for Amp and Tet treatment, resistance persisted 20 h beyond the interruption of treatment. An association between kind of ß-lactam and power of selection was found. SIGNIFICANCE AND IMPACT OF THE STUDY: AMR represents a threat to human health globally and antimicrobial treatment of livestock has a direct impact on this problem. Through our approach based on a swine faecal microcosmos, we demonstrated the effect on AMR development of several drugs commonly used in livestock. Cephalosporins, representing last-line antimicrobials in human medicine, exerted lower selective pressure than Amp under the conditions used and yielded higher proportion of multidrug-R strains.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Fezes/microbiologia , Ampicilina/farmacologia , Animais , Cefalosporinas/farmacologia , Enterobacteriaceae/isolamento & purificação , Suínos , Tetraciclina/farmacologia
13.
J Dairy Sci ; 103(7): 5816-5829, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32418689

RESUMO

Fermented milk is an effective carrier for probiotics, the consumption of which improves host health. The beneficial effects of probiotics, prebiotics, and synbiotics on gut dysbiosis have been reported previously. However, the way in which specific probiotics, prebiotics, and synbiotics regulate intestinal microbes remains unclear. Therefore, the probiotics Lactobacillus rhamnosus AS 1.2466 and Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 and the prebiotics xylooligosaccharide and red ginseng extracts were fed to mice to determine their effects on the intestinal microbiota. Then, mice were administered xylooligosaccharide and L. rhamnosus (synthesis) by gavage, and the number of L. rhamnosus was determined in the intestine at different times. The results show that probiotics and prebiotics can quickly reduce the Firmicutes/Bacteroidetes ratio, inhibit harmful bacteria (such as Klebsiella and Escherichia coli), and accelerate the recovery of beneficial intestinal microorganisms (such as Lactobacillus). In a complex intestinal microecology, different probiotics and prebiotics have different effects on specific intestinal microorganisms that cannot be recovered in the short term. In addition, after 20 d of intragastric xylooligosaccharide addition at 0.12 g/kg of body weight, L. rhamnosus colonization in the mouse ileum was 7.48 log cfu/mL, which was higher than in the low-dose group, prolonging colonization time and increasing the number of probiotics in the intestine. Therefore, this study demonstrated that probiotics and prebiotics can promote the balance of intestinal microbiota by regulating specific microbes in the intestine, and the effects of a suitable combination of synbiotics are beneficial, laying the foundation for the development of new dairy products rich in synbiotics.


Assuntos
Bactérias/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Prebióticos , Probióticos/farmacologia , Simbióticos , Ampicilina/farmacologia , Animais , Antibacterianos/farmacologia , Microbioma Gastrointestinal/fisiologia , Glucuronatos/administração & dosagem , Glucuronatos/farmacologia , Lactobacillus delbrueckii/química , Lactobacillus rhamnosus/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oligossacarídeos/administração & dosagem , Oligossacarídeos/farmacologia , Panax/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Organismos Livres de Patógenos Específicos , Simbióticos/administração & dosagem
14.
Int J Infect Dis ; 95: 148-152, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32278107

RESUMO

BACKGROUND: The rate of surgical site infection (SSI) after pancreaticoduodenectomy (PD) is high and insertion of preoperative bile duct catheterization (PBDC) predispose a high risk of SSI with multidrug resistant (MDR) microorganisms. AIM: To describe the effects of PBDC and the prophylaxis in development of SSI. METHODS: We conducted a retrospective study between January 01, 2010 and December 2018 including the patients with PD and total pancreatectomy. FINDINGS: In total 214 consecutive patients were included. The PBDC was inserted to 63 (29%) patients. The rate of intraoperative bile fluid culture positivity was higher among the patients with PBDC (84% vs. 17% respectively, p<0.001). The SSI was detected in 52 patients (24%). In multivariate analysis, the rate of SSI was found to be higher among the patients with PBDC (OR: 2.33, 95% Cl: 1.14-4.76, p=0.02). As the etiologic agents of SSI, Pseudomonas spp. and MDR pathogens were mainly detected in PBDC group. The resistance to ampicillin-sulbactam was significantly higher in the PBDC group (87.5% vs. 25%, p=0.012). The similar bacterial species both in bile fluid and the surgical site were detected in 11 (21%) patients with SSI. Among 8 patients (15%), antimicrobial susceptibility was the same. Only in five out of 52 (10%) patients, the SSI pathogens was susceptible to the agent that was used for surgical prophylaxis. CONCLUSION: Unnecessary catheterizations should be avoided. By considering the increasing prevalence of resistant bacteria as the cause of SSI, the clinicians should closely follow-up their patients for choosing the proper antimicrobials.


Assuntos
Antibioticoprofilaxia , Pancreaticoduodenectomia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampicilina/farmacologia , Antibacterianos/farmacologia , Bactérias/isolamento & purificação , Bile/microbiologia , Ductos Biliares , Cateterismo , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Cuidados Pré-Operatórios , Pseudomonas/isolamento & purificação , Estudos Retrospectivos , Fatores de Risco , Sulbactam/farmacologia , Infecção da Ferida Cirúrgica/microbiologia , Adulto Jovem
15.
PLoS Biol ; 18(4): e3000465, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32310938

RESUMO

Countering the rise of antibiotic-resistant pathogens requires improved understanding of how resistance emerges and spreads in individual species, which are often embedded in complex microbial communities such as the human gut microbiome. Interactions with other microorganisms in such communities might suppress growth and resistance evolution of individual species (e.g., via resource competition) but could also potentially accelerate resistance evolution via horizontal transfer of resistance genes. It remains unclear how these different effects balance out, partly because it is difficult to observe them directly. Here, we used a gut microcosm approach to quantify the effect of three human gut microbiome communities on growth and resistance evolution of a focal strain of Escherichia coli. We found the resident microbial communities not only suppressed growth and colonisation by focal E. coli but also prevented it from evolving antibiotic resistance upon exposure to a beta-lactam antibiotic. With samples from all three human donors, our focal E. coli strain only evolved antibiotic resistance in the absence of the resident microbial community, even though we found resistance genes, including a highly effective resistance plasmid, in resident microbial communities. We identified physical constraints on plasmid transfer that can explain why our focal strain failed to acquire some of these beneficial resistance genes, and we found some chromosomal resistance mutations were only beneficial in the absence of the resident microbiota. This suggests, depending on in situ gene transfer dynamics, interactions with resident microbiota can inhibit antibiotic-resistance evolution of individual species.


Assuntos
Farmacorresistência Bacteriana/fisiologia , Escherichia coli K12/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Ampicilina/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli K12/genética , Escherichia coli K12/crescimento & desenvolvimento , Escherichia coli K12/fisiologia , Proteínas de Escherichia coli/genética , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Mutação , Plasmídeos
16.
PLoS One ; 15(4): e0231583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294120

RESUMO

Infections caused by antibiotic-resistant strains of Staphylococcus aureus have reached epidemic proportions globally. Our previous study showed antimicrobial effects of anandamide (AEA) and arachidonoyl serine (AraS) against methicillin (MET)-resistant S. aureus (MRSA) strains, proposing the therapeutic potential of these endocannabinoid/endocannabinoid-like (EC/EC-like) agents for the treatment of MRSA. Here, we investigated the potential synergism of combinations of AEA and AraS with different types of antibiotics against MRSA grown under planktonic growth or biofilm formation. The most effective combinations under planktonic conditions were mixtures of AEA and ampicillin (AMP), and of AraS and gentamicin (GEN). The combination with the highest synergy in the biofilm formation against all tested bacterial strains was AEA and MET. Moreover, the combination of AraS and MET synergistically caused default of biofilm formation. Slime production of MRSA was also dramatically impaired by AEA or AraS combined with MET. Our data suggest the novel potential activity of combinations of EC/EC-like agents and antibiotics in the prevention of MRSA biofilm formation.


Assuntos
Antibacterianos/farmacologia , Ácidos Araquidônicos/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Endocanabinoides/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Alcamidas Poli-Insaturadas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Ampicilina/farmacologia , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Ácidos Araquidônicos/uso terapêutico , Biofilmes/efeitos dos fármacos , Agonistas de Receptores de Canabinoides/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Endocanabinoides/uso terapêutico , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Humanos , Resistência a Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Alcamidas Poli-Insaturadas/uso terapêutico , Serina/análogos & derivados , Serina/farmacologia , Serina/uso terapêutico , Infecções Estafilocócicas/microbiologia
17.
Biochemistry ; 59(12): 1217-1220, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32157864

RESUMO

The identification of proteins that bind selectively to nucleic acid sequences is an ongoing challenge. We previously synthesized nucleobase amino acids designed to replace proteinogenic amino acids; these were incorporated into proteins to bind specific nucleic acids predictably. An early example involved selective cell free binding of the hnRNP LL RRM1 domain to its i-motif DNA target via Watson-Crick-like H-bonding interactions. In this study, we employ the X-ray crystal structure of transcriptional regulator Rob bound to its micF promoter, which occurred without DNA distortion. Rob proteins modified in vivo with nucleobase amino acids at position 40 exhibited altered DNA promoter binding, as predicted on the basis of their Watson-Crick-like H-bonding interactions with promoter DNA A-box residue Gua-6. Rob protein expression ultimately controls phenotypic changes, including resistance to antibiotics. Although Rob proteins with nucleobase amino acids were expressed in Escherichia coli at levels estimated to be only a fraction of that of the wild-type Rob protein, those modified proteins that bound to the micF promoter more avidly than the wild type in vitro also produced greater resistance to macrolide antibiotics roxithromycin and clarithromycin in vivo, as well as the ß-lactam antibiotic ampicillin. Also demonstrated is the statistical significance of altered DNA binding and antibiotic resistance for key Rob analogues. These preliminary findings suggest the ultimate utility of nucleobase amino acids in altering and controlling preferred nucleic acid target sequences by proteins, for probing molecular interactions critical to protein function, and for enhancing phenotypic changes in vivo by regulatory protein analogues.


Assuntos
Aminoácidos/química , Proteínas de Ligação a DNA/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/genética , Fatores de Transcrição/metabolismo , Ampicilina/farmacologia , Claritromicina/farmacologia , Cristalografia por Raios X , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Proteínas de Ligação a DNA/química , Escherichia coli/efeitos dos fármacos , Proteínas de Escherichia coli/química , Regulação Bacteriana da Expressão Gênica , Guanina/química , Testes de Sensibilidade Microbiana , Regiões Promotoras Genéticas/genética , RNA Interferente Pequeno/genética , Roxitromicina/farmacologia , Fatores de Transcrição/química
18.
Sci Adv ; 6(10): eaaz5108, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32181369

RESUMO

Much is known about the effects of antibiotics on isolated bacterial species, but their influence on polybacterial communities is less understood. Here, we study the joint response of a mixed community of nonresistant Bacillus subtilis and Escherichia coli bacteria to moderate concentrations of the ß-lactam antibiotic ampicillin. We show that when the two organisms coexist, their population response to the antibiotic is opposite to that in isolation: Whereas in monoculture B. subtilis is tolerant and E. coli is sensitive to ampicillin, in coculture it is E. coli who can proliferate in the presence of the antibiotic, while B. subtilis cannot. This antithetic behavior is predicted by a mathematical model constrained only by the responses of the two species in isolation. Our results thus show that the collective response of mixed bacterial ecosystems to antibiotics can run counter to what single-species potency studies tell us about their efficacy.


Assuntos
Ampicilina/farmacologia , Antibacterianos/farmacologia , Bacillus subtilis/crescimento & desenvolvimento , Escherichia coli/crescimento & desenvolvimento , Consórcios Microbianos/efeitos dos fármacos , Modelos Biológicos , Resistência beta-Lactâmica , Técnicas de Cocultura
19.
J Med Chem ; 63(7): 3737-3755, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32196336

RESUMO

The ability of 6-(aryl)methylidene penicillin-based sulfones 1-7 to repurpose ß-lactam antibiotics activity with bacterial species that carry carbapenem-hydrolyzing class D ß-lactamases (OXA-23, OXA-24/40 and OXA-48), as well as with class A (TEM-1, CTX-M-2) and class C (CMY-2, DHA-1) enzymes, is reported. The combinations imipenem/3 and imipenem/4 restored almost completely the antibiotic efficacy in OXA-23 and OXA-24/40 carbapenemase-producing A. baumannii strains (1 µg mL-1) and also provided good results for OXA-48 carbapenemase-producing K. pneumoniae strains (4 µg mL-1). Compounds 2-6 in combinations with ceftazidime and ampicillin were also efficient in restoring antibiotic efficacy in E. coli strains carrying class C (CMY-2 and DHA-1) and class A (TEM-1 and CTX-M-2) ß-lactamase enzymes, respectively. Kinetic and inhibition studies with the OXA-24/40 enzyme, protein mass spectrometry analysis and docking studies allowed us to gain an insight into the inhibition mechanism and the experimentally observed differences between the ligands.


Assuntos
Antibacterianos/farmacologia , Penicilinas/farmacologia , Sulfonas/farmacologia , Inibidores de beta-Lactamases/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Ampicilina/farmacologia , Antibacterianos/síntese química , Antibacterianos/metabolismo , Domínio Catalítico , Ceftazidima/farmacologia , Reposicionamento de Medicamentos , Escherichia coli/efeitos dos fármacos , Imipenem/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Penicilinas/síntese química , Penicilinas/metabolismo , Ligação Proteica , Sulfonas/síntese química , Sulfonas/metabolismo , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/metabolismo , beta-Lactamases/química , beta-Lactamases/metabolismo
20.
Int J Mol Sci ; 21(3)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023867

RESUMO

The development of inclusion complexes is used to encapsulate nonpolar compounds and improve their physicochemical characteristics. This study aims to develop complexes made up of Euterpe oleracea Mart oil (EOO) and ß-cyclodextrin (ß-CD) or hydroxypropyl-ß-cyclodextrin (HP-ß-CD) by either kneading (KND) or slurry (SL). Complexes were analyzed by molecular modeling, Fourier-transform infrared spectroscopy, scanning electron microscopy, powder X-ray diffraction, thermogravimetry analysis and differential scanning calorimetry. The antibacterial activity was expressed as Minimum Inhibitory Concentration (MIC), and the antibiotic resistance modulatory activity as subinhibitory concentration (MIC/8) against Escherichia coli, Streptomyces aureus, Pseudomonas aeruginosa and Enterococcus faecalis. Inclusion complexes with ß-CD and HP-ß-CD were confirmed, and efficiency was proven by an interaction energy between oleic acid and ß-CD of -41.28 ± 0.57 kJ/mol. MIC values revealed higher antibacterial activity of complexes compared to the isolated oil. The modulatory response of EOO and EOO-ß-CD prepared by KND as well as of EOO-ß-CD and EOO-HP-ß-CD prepared by SL showed a synergistic effect with ampicillin against E. coli, whereas it was not significant with the other drugs tested, maintaining the biological response of antibiotics. The antimicrobial response exhibited by the complexes is of great significance because it subsidizes studies for the development of new pharmaceutical forms.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Antibacterianos/farmacologia , Euterpe/química , Óleos Vegetais/química , beta-Ciclodextrinas/farmacologia , 2-Hidroxipropil-beta-Ciclodextrina/química , Ampicilina/farmacologia , Antibacterianos/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Sinergismo Farmacológico , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Streptomyces/efeitos dos fármacos , beta-Ciclodextrinas/química
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